nus_datathon_workshop_Data

disease.csv

ko,name,description,disease_category
"H02108","Basal laminar drusen","Basal laminar drusen (BLD, also termed cuticular drusen or early adult onset grouped drusen) is an early-onset-drusen phenotype that shows a pattern of uniform small (25 to 75 micrometer), slightly raised, yellow subretinal nodules randomly scattered in the macula. In later stages, these drusen often become more numerous, with clustered groups of drusen scattered throughout the retina. It has been reported that a variant in CFH gene is strongly associated with this disease.","Nervous system disease"
"H00835","Succinic semialdehyde dehydrogenase deficiency","Succinic semialdehyde dehydrogenase (SSADH) deficiency, also known as 4-hydroxybutyric aciduria (4-HBA), is an autosomal recessive inborn error of metabolism. Clinical features include intellectual disability with prominent deficits in expressive language, hypotonia, nonprogressive ataxia, and hyporeflexia. The causative gene is aldehyde dehydrogenase 5 family, member A1 (ALDH5A1) encoding SSADH. SSADH is deficient in affected individuals impairing the formation of succinic acid from succinic semialdehyde and leading to the increased production of 4-HBA.","Inherited metabolic disease"
"H00009","Adult T-cell leukemia","Adult T-cell leukemia (ATL) is one of the most aggressive hematologic malignancies and is caused by human T-cell leukemia virus type 1 (HTLV-1). The HTLV-1 Tax protein has been demonstrated to be the oncogenic protein of the virus. Tax may contribute to the process of carcinogenesis by a variety of mechanisms, including upregulating the expression of cellular genes involved in T cell growth and proliferation, including IL-2, IL-2R-alpha, and IL-15. However, ATL cells do not always need Tax expression in the later stage of leukemogenesis. Genetic and epigenetic changes should be implicated in such multistep leukemogenesis. Regarding genetic changes, mutation of p53, and deletion of p16 have been reported in ATL. Mutations of Fas gene are also reported in patients with ATL cells. However, such genetic changes were not frequently detected. In this regard, epigenetic change of p16/INK4A gene was more frequent in ATL cells, and accumulated according to the disease progression. This finding suggests that epigenetic change, including DNA methylation, plays an important role in the leukemogenesis of ATL.","Cancer"
"H01913","Renpenning syndrome","Renpenning syndrome is a group of X-linked mental retardation syndromes, caused by mutations in human polyglutamine-binding protein 1 (PQBP1) gene. It is characterized by intellectual deficiency, microcephaly, short stature, and microrchidia. PQBP1 plays important roles in neurodevelopment and neuronal functions. It is thought to interact with RNA polymerase, transcription factors, and spliceosome proteins, and thus to act as a transcription and splicing regulator.","Congenital malformation"
"H01779","Neuroferritinopathy","Neuroferritinopathy is a rare autosomal dominant disease caused by mutations in the ferritin light chain (FTL) gene leading to abnormal excessive iron accumulation in the brain, predominantly in the basal ganglia. Clinically, the disease presents as a chorea and dystonia. Clinical presentation may also include extrapyramidal and pyramidal tract signs as well as cerebellar ataxia, dysautonomia, cognitive decline, and psychiatric symptoms.","Neurodegenerative disease"
"H00499","Spondylocarpotarsal synostosis syndrome","Spondylocarpotarsal synostosis syndrome is an autosomal recessive disease characterized by the malsegmentation of vertebrae and the fusion of carpal and tarsal bones. Retinal anomalies and hearing loss are also observed. Spondylocarpotarsal synostosis syndrome is due to FLNB mutations.","Congenital malformation"
"H00204","Infantile Refsum disease","Infantile Refsum disease (IRD) is an autosomal recessive peroxisome biogenesis disorder, whose clinical and biochemical features are different from the adult form of Refsum disease. IRD is characterized by delayed development, mental retardation, hepatomegaly, and skeletal changes.","Inherited metabolic disease"
"H00036","Osteosarcoma","Osteosarcoma is the most common type of primary bone cancer. Approximately 900 new cases of osteosarcoma are diagnosed each year in the United States. The presentation of this disease is bimodal, with peaks in adolescence and after the age of 50 years. The tumors typically arise in the metaphyseal regions of long bones, with the distal femur, proximal tibia, and proximal humerus representing the three most common sites. Genomic amplification, especially of both the p53-binding MDM2 gene and the flanking SAS gene, plays an important role in the biology of these tumors. Alterations of Rb1 and c-myc are also common, and mutations have been reported in p53, p16INK4A, and CDKN2B.","Cancer"
"H00452","Buschke-Ollendorff syndrome","Buschke-Ollendorff syndrome (BOS), also known as Osteopoikilosis, is a disorders characterized by increased bone density. Loss-of-function mutations in LEMD3, which encodes an inner nuclear membrane protein can result in these conditions. LEMD3 is thought to be involved in Smad signaling.","Congenital malformation"
"H01580","Vitamin C deficiency","Scurvy occurs because of reduced intake or absorption of vitamin C, which is characterized by bleeding gums, impaired wound healing, petechiae, perifollicular hemorrhage, anemia, arthralgia and joint effusions, fatigue, depression, and sudden death. It appears to result primarily from the decreased synthesis of collagen, a major protein in the body dependent on vitamin C for its biosynthesis. However, this role of vitamin C does not explain all of the manifestations associated with scurvy. At-risk groups include the poor (because of reduced access to groceries), food faddists, and individuals with purported allergies to multiple fruit and vegetable products. Other at-risk groups include persons with gastrointestinal disease (e.g. colitis), anatomical abnormalities, poor dentition, cancer patients on chemotherapy, patients on hemodialysis, and psychiatric disorders (e.g. depression, schizophrenia, or anorexia). Alcoholic persons represent one of the largest groups at risk for scurvy because they may have poorly balanced diets and because alcohol decreases the absorption of vitamin C. The diagnosis of scurvy is generally based on clinical features and dietary history, and there is rapid resolution of signs and symptoms after vitamin C supplementation.","Hematologic disease; Cardiovascular disease; Metabolic disease"
"H02305","RERE-related neurodevelopmental syndrome","RERE-related neurodevelopmental syndrome, also known as neurodevelopmental disorder with or without anomalies of the brain, eye, or heart (NEDBEH), is a rare autosomal dominant disorder. Patients with intellectual disability, developmental delay, and autism spectrum disorder who carry mutations in RERE have been described. RERE is a widely-expressed nuclear receptor coregulator that positively regulates retinoic acid signaling.","Mental and behavioural disorder"
"H02137","Laurence-Moon syndrome","Laurence-Moon syndrome is caused by mutations in the PNPLA6 gene, encoding neuropathy target esterase (NTE). It is characterised by chorioretinopathy, pituitary dysfunction, childhood onset of ataxia, and spastic paraplegia. Polydactyly and renal disease are absent. So it is distinct from Bardet-Biedl syndrome.","Nervous system disease"
"H00660","Congenital contractural arachnodactyly","Congenital contractural arachnodactyly (CCA) or Beals syndrome is an autosomal dominant disorder characterized by a Marfan-like appearance and arachnodactyly. Most affected individuals have 'crumpled' ears, contractures of major joints, and camptodactyly. Additional features include muscular hypoplasia and scoliosis. In contrast to Marfan syndrome, CCA does not affect the aorta or the eyes.","Congenital malformation"
"H01574","Familial idiopathic basal ganglia calcification","Familial idiopathic basal ganglia calcification, also known as Fahr disease, is an inherited neurological disorder characterized by symmetrical calcification of cerebral structures lacking known metabolic causes such as calcium or phosphorus homeostasis disorders. Currently, autosomal dominant and recessive causative genes have been identified.","Nervous system disease"
"H00694","Dent disease","Dent disease is a renal tubular disorder characterized by manifestations of proximal tubule dysfunction, including low-molecular-weight proteinuria, hypercalciuria, nephrolithiasis, nephrocalcinosis, and progressive renal failure. The disease is caused by mutations in either the CLCN5 or OCRL1 genes. CLCN5 encodes a member of the ClC family of chloride ion channels and ion transporters. OCRL1 encodes a phosphatidylinositol bisphosphate (PIP2) 5-phosphatase and mutations are also associated with Lowe Syndrome.","Urinary system disease"
"H01746","STING-associated vasculopathy with onset in infancy","STING (stimulator of interferon genes)-associated basculopathy with onset in infancy (SAVI) is a rare hereditary autoinflammatory disorder caused by gain-of-function mutations in TMEM173, the gene encoding the STING protein. It is considered that the mutations in the TMEM173 gene confer constitutive activation of STING and hypersensitivity to ligand stimulation, resulting in chronic activation of the STING-interferon pathway. Patients with SAVI have severe neonatal-onset small vessel vasculitis, which is expressed by telangiectatic ulcerative rashes in the limbs, earlobes, or nose, leading to microangiopathic thrombosis, vessel occlusion, and even risk of gangrene. Some SAVI patients may present chronic interstitial lung disease, which can be severe and lethal.","Immune system disease"
"H01322","Kyasanur Forest disease","Kyasanur Forest disease is a viral hemorrhagic fever caused by Kyasanur Forest disease (KFDV), a flavivirus in the Flaviviridae family of +ssRNA viruses, and transmitted by Ixodoidea ticks. KFDV was first isolated 1957 in India.","Infectious disease"
"H01110","Pneumothorax","Pneumothorax is defined as air or gas accumulated in the pleural space and can be classified as spontaneous or traumatic. Traumatic pneumothorax includes iatrogenic cases caused during procedures such as pacemaker insertion. Spontaneous pneumothorax can be subclassified as primary or secondary. Primary spontaneous pneumothorax (PSP), which is defined as a pneumothorax without underlying lung disease, predominantly occurs in young, thin males. It is usually caused by ruptured pleural blebs or bullae. Approximately 10% of patients with PSP have a positive family history. Gene mutations in folliculin (FLCN) have been found.","Respiratory disease"
"H01914","Christianson syndrome","Christianson syndrome (CS) is a rare, X-linked mental retardation syndrome, caused by mutations in SLC9A6. CS is characterized by severe intellectual disability, microcephaly, epilepsy, ataxia, and absent speech. The clinical phenotype of CS mimics Angelman syndrome and CS was initially called X-linked Angelman-like syndrome.","Congenital malformation"
"H01128","Reticular dysgenesis","Reticular dysgenesis (RD) is a rare congenital immunodeficiency classified within the severe combined immunodeficiencies (SCIDs). It is inherited in an autosomal recessive manner, and is characterized by absence of granulocytes and almost complete deficiency of lymphocytes in peripheral blood, hypoplasia of the thymus and secondary lymphoid organs, and lack of innate and adaptive humoral and cellular immune functions, leading to fatal septicemia within days after birth. The bone marrow showed a maturation arrest in the myeloid and lymphoid lineage. The underlying genetic defect for most cases of RD have been identified in the gene encoding adenylate kinase 2 (AK2).","Immune system disease"
"H00832","Core neuroacanthocytosis syndromes","Neuroacanthocytosis (NA) syndromes are a heterogeneous group of diseases in which nervous system abnormalities coincide with red blood cell acanthocytosis. Core NA syndromes are one of the broad groups of NA disorders characterized by degeneration of the basal ganglia, movement disorders, cognitive impairment, and psychiatric features. NA syndromes are caused by disease-specific genetic mutations. The mechanism by which these mutations cause neurodegeneration is not known.","Nervous system disease"
"H00658","Syndromic X-linked mental retardation","X-linked mental retardation (MRX) is an inherited condition that causes failure to develop cognitive abilities because of mutations in several genes on the X chromosome. XLMR is subdivided into syndromic and non-syndromic forms, depending on whether further abnormalities are found or not. Syndromic XLMR is characterized by recognizable dysmorphic features, neurological complications, and/or metabolic abnormalities.","Mental and behavioural disorder"
"H01117","Chronic recurrent multifocal osteomyelitis","Chronic recurrent multifocal osteomyelitis (CRMO), also known as Majeed syndrome, is a rare, autosomal recessive autoinflammatory disorder consisting of chronic recurrent multifocal osteomyelitis, congenital dyserythropoietic anemia, and neutrophilic dermatosis. It has been reported that mutations in LPIN2 are responsible for this syndrome.","Inherited metabolic disease; Immune system disease"
"H01325","Actinomycosis","Actinomycosis is an uncommon chronic granulomatous infection caused by several members of the order Actinomycetales, most notably, Actinomyces israelii. Additional species that are established but less common causes of actinomycosis include A. naeslundii/viscosus complex, A. odontolyticus, A. meyeri and A. gerencseriae.","Infectious disease"
"H00693","Ichthyosis bullosa of Siemens","Ichthyosis Bullosa of Siemens (IBS) is an autosomal dominant disorder characterized by mild hyperkeratosis and blister formation. The blistering is superficial, and areas of peeling of the skin are known as the 'Mauserung phenomenon'. IBS shows similar features to those in epidermolytic hyperkeratosis, but can be distinguished by the absence of erythema.","Congenital malformation"
"H01741","Autoinflammation lipodystrophy and dermatosis syndrome","Autoinflammation lipodystrophy and dermatosis syndrome (ALDD) is a systemic inflammatory condition characterized by recurrent episodes of fever, cutaneous lesions, lipodystrophy, and visceral inflammatory manifestations. In 2011, several studies showed that a number of disorders referred to as joint contractures, muscle atrophy, microcytic anemia, and panniculitis-induced lipodystrophy (JMP) syndrome, Nakajo-Nishimura syndrome, Japanese autoinflammatory syndrome with lipodystrophy (JASL), and chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome are caused by mutations in proteasome subunit beta type 8 (PSMB8) gene, indicating that these disorders are disease phenotypes along the same disease spectrum. Key symptoms include a persistent fever (higher than 38.5 degrees Celsius), steroid-sensitive erythema nodosum-like (edematous and purpuric) plaques, long clubbed fingers, hyperhidrosis, myositis, hepatosplenomegaly, macroglossia, facial and limbs lipoatrophy, and developmental (height, weight, and IQ) retardation. Skin biopsies show immature myeloid-lineage cells with mitoses. Some patients may have joint contracture, auricular and nasal chondritis, and calcification of the basal ganglia. Acute cardiovascular event is the leading cause of death in these patients for whom life expectancy is notably reduced. Management of these patients is by palliative care. The need for steroids is very high even in combination with anti IL-1, anti IL-6 or anti-TNF treatments.","Immune system disease"
"H01573","Zimmermann-Laband syndrome","Zimmermann-Laband syndrome (ZLS) is a rare craniofacial malformation syndrome with predominant intraoral involvement consisting in diffuse gingival fibromatosis of early onset. Most cases are sporadic, suggesting autosomal dominant inheritance with de novo mutations. The main clinical characteristics of ZLS are gingival enlargement, prominent nose and thick ears with soft cartilages, nail aplasia or hypoplasia, hypertrichosis, joint hyperextensibility, hepato(spleno)megaly, and intellectual disability with or without epilepsy. Mutations in KCNH1 and ATP6V1B2 account for a proportion of ZLS.","Congenital malformation"
"H02130","Mucolipidosis III","Mucolipidosis type III (MLIII), or pseudo-Hurler polydystrophy, is an autosomal recessive disorder affecting lysosomal hydrolase trafficking. The clinical phenotype is variable, and some MLIII patients survive to adulthood. MLIII is caused by the deficiency of GlcNac-1-phosphotransferase, that is exists as a heterohexamer comprising three subunits, alpha, beta, and gamma. It is encoded by two distinct genes, GNPTAB and GNPTAG.","Congenital disorder of metabolism"
"H00667","Woolly hair","Woolly hair (WH) is a group of hair shaft dystrophies characterized by fine and tightly curled hair. WH is inherited in either autosomal dominant and autosomal recessive manner. Autosomal recessive woolly hair can also show varying degrees of sparse hair or hypotrichosis (HYPT).","Congenital malformation"
"H00455","Spinal muscular atrophy","Spinal muscular atrophy (SMA) is a neuromuscular disease characterized by degeneration of motor neurons, resulting in progressive muscle atrophy and paralysis. The most common form of SMA is caused by mutations of the SMN gene, that encodes the SMN protein, which regulates snRNP assembly. Four types of SMA are recognized depending on the age of onset and the severity of the disease: type I (Werdning-Hoffman), type II (intermediate), type III (Kugeleberg-Welander) and type IV (adult form). Other forms of spinal muscular atrophy are caused by mutation of other genes, some known and others not yet defined.","Neurodegenerative disease"
"H01587","Disseminated intravascular coagulation","Disseminated intravascular coagulation (DIC) is an acquired syndrome characterised by the intravascular activation of coagulation with loss of localisation arising from different causes. It can originate from and cause damage to the microvasculature, which if sufficiently severe, can produce organ dysfunction. DIC is not a disease entity on itself but is always associated to an underlying disease. The clinical conditions that may be associated with DIC include sepsis, trauma, malignancy, liver disease, obstetric disorders, envenomation, vascular anomalies, and major transfusion reactions. A diagnosis of DIC should be made only in the presence of a clinical condition (causative factor) supported by repeated laboratory tests for coagulation profile and clotting factors. Treatment of DIC is aimed at combating the underlying disorder followed by supportive management.","Hematologic disease"
"H02302","Hepatoblastoma","Although malignant tumors of the liver are rare during childhood, hepatoblastoma is the most common liver cancer in children, usually diagnosed during the first 3 years of life. These tumors are thought to arise from hepatic progenitors or hepatoblasts. The most frequent genetic aberrations (70-90%) in hepatoblastoma occur in genes involved in the Wnt signaling pathway. The Wnt signaling pathway is activated often by acquired activating mutations of the beta-catenin (CTNNB1) gene, and less commonly through constitutional mutations of the APC gene or somatic mutations of other genes in the pathway.","Cancer"
"H00031","Breast cancer","Breast cancer is the leading cause of cancer death among women worldwide. The vast majority of breast cancers are carcinomas that originate from cells lining the milk-forming ducts of the mammary gland. The molecular subtypes of breast cancer, which are based on the presence or absence of hormone receptors (estrogen and progesterone subtypes) and human epidermal growth factor receptor-2 (HER2), include: hormone receptor positive and HER2 negative (luminal A subtype), hormone receptor positive and HER2 positive (luminal B subtype), hormone receptor negative and HER2 positive (HER2 positive), and hormone receptor negative and HER2 negative (basal-like or triple-negative breast cancers (TNBCs)). Hormone receptor positive breast cancers are largely driven by the estrogen/ER pathway. In HER2 positive breast tumours, HER2 activates the PI3K/AKT and the RAS/RAF/MAPK pathways, and stimulate cell growth, survival and differentiation. In patients suffering from TNBC, the deregulation of various signalling pathways (Notch and Wnt/beta-catenin), EGFR protein have been confirmed. In the case of breast cancer only 8% of all cancers are hereditary, a phenomenon linked to genetic changes in BRCA1 or BRCA2. Somatic mutations in only three genes (TP53, PIK3CA and GATA3) occurred at >10% incidence across all breast cancers.","Cancer"
"H00203","Acatalasemia","Acatalasia is an autosomal recessive peroxisomal disorder caused by deficiency of erythrocyte catalase that metabolizes both hydrogen peroxide and a variety of substrates such as ethanol, methanol, phenol and nitrites. Catalase has an important protective function against the toxic effects of peroxides generated in peroxisomes and removes them with high efficiency. The Japanese, Swiss, and Hungarian types of acatalasemia display differences in biochemical and genetic aspects. Takahara's disease shows progressive oral gangrene and formerly occurred in about half of Japanese acatalasemia patients.","Congenital disorder of metabolism"
"H01922","Infantile hypotonia with psychomotor retardation and characteristic facies","Infantile hypotonia with psychomotor retardation and characteristic facies (IHPRF) is an autosomal-recessive syndrome characterized by subtle facial dysmorphism, variable degrees of hypotonia, speech impairment, chronic constipation, and intellectual disability. It is caused by mutations in the cation channel NALCN and UNC80. NALCN has a role in basal sodium ion leak conductance in neurons, essential for neuronal function. UNC80 bridges between UNC79 and NALCN. Recently, pathogenic biallelic variants in TBC1-domain-containing kinase (TBCK) were also identified.","Congenital malformation"
"H01748","Autoinflammation with infantile enterocolitis","Autoinflammation with infantile enterocolitis (AIFEC) is a rare autosomal dominant disease characterized by neonatal-onset enterocolitis, periodic fever, and fatal/near-fatal episodes of autoinflammation. It was shown that the disease is caused by gain-of-function mutations in NLRC4. NLRC4 protein is known to directly assemble inflammasomes that activate IL-1beta and IL-18.","Immune system disease"
"H02139","Autosomal recessive hypophosphatemic rickets","Autosomal recessive hypophosphatemic rickets (ARHR) is a rare form of hypophosphatemic rickets that is caused by mutations in the DMP1 gene. DMP1 is highly expressed in mineralized tissues, especially in osteoblasts and osteocytes, and is a key regulatory protein that is required for the normal growth and development of bone, cartilage and dentin. Recently, ARHR associated with a mutation in the ENPP1 gene has also been reported.","Congenital disorder of metabolism"
"H00804","Multiple cutaneous and uterine leiomyomata","Multiple cutaneous and uterine leiomyomatosis (MCUL) is a rare autosomal dominant disorder that affects both sexes. It is characterized by benign skin tumors arising from the arrector pili muscle, and from uterine fibroids in female patients. Some patients with MCUL develop renal cancer and this condition is called hereditary leiomyomatosis and renal cell cancer.","Cancer"
"H00038","Melanoma","Melanoma is a form of skin cancer that has a poor prognosis and which is on the rise in Western populations. Melanoma arises from the malignant transformation of pigment-producing cells, melanocytes. The only known environmental risk factor is exposure to ultraviolet (UV) light and in people with fair skin the risk is greatly increased. Melanoma pathogenesis is also driven by genetic factors. Oncogenic NRAS mutations activate both effector pathways Raf-MEK-ERK and PI3K-Akt. The Raf-MEK-ERK pathway may also be activated via mutations in the BRAF gene. The PI3K-Akt pathway may be activated through loss or mutation of the inhibitory tumor suppressor gene PTEN. These mutations arise early during melanoma pathogenesis and are preserved throughout tumor progression. Melanoma development has been shown to be strongly associated with inactivation of the p16INK4a/cyclin dependent kinases 4 and 6/retinoblastoma protein (p16INK4a/CDK4,6/pRb) and p14ARF/human double minute 2/p53 (p14ARF/HMD2/p53) tumor suppressor pathways. MITF and TP53 are implicated in further melanoma progression.","Cancer"
"H01777","Schwartz-Jampel syndrome","Schwartz-Jampel syndrome (SJS) is a rare hereditary disorder with joint contractures, generalized myotonia, skeletal anomalies, and facial dysmorphism. Schwartz-Jampel syndrome (SJS) is a term now applied to 2 different autosomal recessive disorder, sometimes termed SJS type 1 and SJS type 2. SJS type 1 results from mutations in the HSPG2 gene, which encodes perlecan, a major component of basement membranes. It exhibits muscle stiffness, mild muscle weakness, and a number of minor morphological abnormalities. In affected patients, problems with motor development frequently become evident during the first year of life. SJS type 2, also known as Stuve-Wiedemann syndrome [DS:H00462], is a genetically distinct disorder with a more severe phenotype.","Nervous system disease; Musculoskeletal disease"
"H01545","O'nyong-nyong fever","O'nyong-nyong fever is an infectious disease caused by O'nyong-nyong virus (ONNV), an alphavirus in the Togaviridae family of +ssRNA viruses, and transmitted by Anopheles mosquitoes. ONNV was first isolated in 1959 in Uganda.","Infectious disease"
"H00497","Cherubism","Cherubism is an uncommon disorder of the jaws in childhood. The maxillary bones are replaced with pseudocystic osteolytic lesions, affecting dentition. Mutated SH3BP2, which can enhance BCR signaling, is involved in the pathogenesis of cherubism.","Digestive system disease"
"H01121","Succinyl CoA:3-oxoacid CoA transferase (SCOT) deficiency","Succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency is an inborn error of ketone body metabolism. SCOT/OXCT1 is a key mitochondrial enzyme in the metabolism of ketone bodies in various organs. Deficiency of SCOT activity inhibits peripheral ketone body utilization and causes episodes of severe ketoacidosis.","Inherited metabolic disease"
"H01313","Escherichia coli meningitis","Escherichia coli meningitis is a bacterial meningitis caused by Escherichia coli, and is common in the newborn within the first month of life (neonatal meningitis). Neonatal meningitis-associated Escherichia coli (NMEC) strains possessing the K1 capsular polysaccharide is a major cause of neonatal meningitis.","Infectious disease"
"H00007","Hodgkin lymphoma","Hodgkin's lymphoma (HL) is one of the most frequent lymphomas in the Western world and often affects young adults. HL is subdivided into classical and nodular lymphocyte-predominant forms. About 95% of cases are classical HL, and 5% are nodular lymphocyte-predominant HL (NLPHL). A characteristic feature of HL is the rareness of the tumor cells, which are called Hodgkin's and Reed/Sternberg (HRS) cells in classical HL and lymphocytic and histiocytic (L&H) cells in NLPHL. These cells represent only about 1% of the cellular infiltrate, while the vast majority of infiltrating cells are T lymphocytes, histiocytes, eosinophilic granulocytes and plasma cells. HRS cells show constitutive activity of both the classical and alternative NF-{kappa}B signalling pathways, which is probably a major pathogenetic mechanism in Hodgkin's lymphoma. The NF-{kappa}B activity in HRS cells is probably mediated by diverse mechanisms: receptor signalling through CD40, RANK, BCMA, and TACI, genomic REL amplification, destructive mutations in IKBA and IKBE. In HL pathogenesis associated with Epstein-Barr virus infection, the activation of NF-{kappa}B is induced by viral latent membrane protein 1 (LMP1).","Cancer"
"H00235","Methemoglobinemia","Hereditary methemoglobinemia is an autosomal recessive disorder characterized by NADH-cytochrome b5 reductase deficiency.","Hematologic disease"
"H01783","Ebstein anomaly","Ebstein anomaly is a rare congenital heart abnormality, characterized by downward displacement of the tricuspid valve into the right ventricle. Displacement and malformation of the tricuspid valve is accompanied by an enlarged right atrium and a dilated, thinned right ventricle. Ebstein anomaly can occur as a sporadic or a familial defect. It has been reported that deletion 1p36 and deletion 8p23.1 are the most frequent chromosomal structural changes associated with Ebstein anomaly.","Developmental disorder; Cardiovascular disease"
"H00651","Hypohidrotic ectodermal dysplasia","Hypohidrotic ectodermal dysplasia (HED) is a condition characterized by major involvement of ectodermal structures with perturbed formation and maturation of teeth, hair, and sweat glands. HED is caused by defective epithelial-mesenchymal interaction that involves the Ectodysplasin/Edar/Edaradd signaling pathway. Congenital anhidrotic ectodermal dysplasia is a sex-linked disorder characterized by incomplete development of the dermis, resulting in the absence of hair follicles and sweat glands with anodontia in affected males.","Congenital malformation"
"H02106","Genetic obesity","Obesity predisposes to many diseases. It has a very heterogeneous phenotypic expression and the molecular mechanisms involved in its development are diverse. Although environmental factors are important, genes also have a significant role in its pathogenesis. Several genes that are involved in monogenic, syndromic and polygenic obesity, have been identified.","Endocrine and metabolic disease"
"H02334","Pierpont syndrome","Pierpont syndrome is a rare disorder characterized by developmental delay, characteristic facial gestalt, hearing loss, and abnormal fat distribution in the distal limbs. Mutations in TBL1XR1 has been described recently in patients with this disease.","Congenital malformation"
"H00463","Currarino syndrome","Currarino syndrome is a condition characterized by the combination of sacral malformation, hindgut anomaly, and presacral mass. The HLXB9 gene is responsible for the symdrome.","Congenital malformation"
"H00803","Seizures-sensorineural deafness-ataxia-mental retardation-electrolyte imbalance (SESAME)","Seizures-sensorineural deafness-ataxia-mental retardation-electrolyte imbalance (SESAME) is a channelopathy characterized by seizures, sensorineural deafness, ataxia, intellectual deficit, and electrolyte imbalance. This disease links to autosomal recessive mutations in KCNJ10, which encodes the potassium channel.","Nervous system disease"
"H00669","Naxos disease","Naxos disease is characterized by cardiomyopathy, palmoplantar keratoderma, and woolly hair. Cardiac manifestation in patients with Naxos disease is arrhythmogenic right ventricular cardiomyopathy that appears by adolescence.","Congenital malformation"
"H01589","Systemic primary carnitine deficiency","Systemic primary carnitine deficiency is a rare autosomal recessive disorder characterized by cardiomyopathy, muscle weakness, hypoglycemic hypoketotic coma, and hyperammonemia. Carnitine plays essential roles in the transportation of long-chain fatty acids into the mitochondria for beta-oxidation. This disease is caused by mutations in SLC22A5 that encodes the high-affinity sodium-dependent carnitine transporter, organic cation transporter 2 (OCTN2). The hallmark of systemic primary carnitine deficiency is low concentrations of carnitine in plasma, with accumulation of lipid deposits and renal leakage of carnitine. The clinical symptoms are alleviated dramatically by oral administration of L-carnitine. However, if untreated, patients are precipitated into a crisis with cardiac arrest or Reye-like syndrome that includes acute encephalopathy and fatty degenerative liver failure.","Congenital disorder of metabolism"
"H01925","Transient neonatal zinc deficiency","Transient neonatal zinc deficiency (TNZD) is a disorder caused by loss-of-function mutations of the zinc transporter SLC30A2/ZnT2 gene, which results in low zinc breast milk in the mother, consequently causing zinc deficiency in the breast-fed infant. The main initial symptoms of zinc deficiency are dermatitis, diarrhea, alopecia, and loss of appetite. Currently, at least two zinc transporters from separate protein families are now known to be involved in the genetics of zinc deficiency. One is SLC39A4/ZIP4, which mutations can cause acrodermatitis enteropathica (AEZ) [DS:H00212] with autosomal recessive inheritance. The other one is SLC30A2/ZnT2, the transporter responsible for supplying human milk with zinc. Mutations in this transporter cause TNZD with symptoms similar to AE but with autosomal dominant inheritance. The two diseases can be distinguished in affected infants. AE is fatal if zinc is not supplied to the infant after weaning, whereas TNZD is a genetic defect of the mother limiting the supply of zinc in the milk, and therefore the infant usually will obtain enough zinc once weaned. Furthermore, the mothers' blood zinc levels are normal, and zinc supplementation to the mother's diet fails to improve the zinc levels in the breast milk.","Skin and connective tissue disease; Gastrointestinal disease"
"H01119","Prolidase deficiency","Prolidase deficiency (PD) is a severe autosomal recessive disorder due to the lack of prolidase (EC:3.4.13.9), a peptidase with a preference for Xaa-Pro dipeptide substrates that participates in collagen metabolism and in the terminal degradation of endogenous and dietary proteins. It typically begins in childhood and common symptoms include chronic intractable skin ulcerations and mental retardation. Mutations in prolidase gene causing the reduction or the loss of prolidase activity are responsible for PD.","Inherited metabolic disease"
"H02333","Laurin-Sandrow syndrome","Laurin-Sandrow syndrome (LSS) is a rare autosomal dominant disorder characterized by polysyndactyly of hands and/or feet, mirror image duplication of the feet, and nasal defects. It has been shown that small microduplications within the ZRS region are the underlying genetic cause of LSS. ZRS is highly conserved in all vertebrates with limb appendages and consists of an 800bp enhancer sequence located within intron 5 of LMBR1.","Congenital malformation"
"H00464","Nail-patella syndrome","Nail-patella syndrome is a condition caused by mutation in LMX1B that regulates COL4A4 and COL4A3 expression. The most common associated abnormality is nail dysplasia.","Congenital malformation"
"H01784","Primary hyperchylomicronemia","Primary hyperchylomicronemia is characterized by a marked hypertriglyceridemia due to the accumulation of chylomicron occurs in the circulation. The main clinical symptoms of this disorder are the huge increase in plasma trigriceride and cholesterol, and the presence of xanthomatous eruption, lipemia retinalis, hepatosplenomegaly, and the complication of acute pancreatitis. The genetic basis for primary hyperchylomicronemia is heterogeneous. The familial chylomicronemia (known as Fredrickson's classification of type 1 hyperlipoproteinemia) [DS:H00154] is a clinical condition showing the severest hypertriglyceridemia and is classically represented by two rare genetic disorders, i.e., familial lipoprotein lipase (LPL) deficiency and familial apolipoprotein C-II deficiency. Even rarer conditions such as circulating inhibitor of lipoprotein lipase and the presence of autoantibodies also cause type 1 hyperlipoproteinemia. More recently, patients with primary hyperchylomicronemia caused by mutations in the gene for glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1) or lipase maturation factor 1 (LMF1). By contrast, the more commonly encountered polygenic chylomicronemia of adulthood, referred to as mixed dyslipidemia (known as type 5 hyperlipoproteinemia) [DS:H00157], can present later in life and is characterized by increased levels of hepatically derived triglyceride-rich lipoproteins and triglyceride-rich remnant particles together with reduced levels of HDL cholesterol.","Inherited metabolic disease; Cardiovascular disease"
"H00656","Scapuloperoneal myopathy","Scapuloperoneal syndrome encompasses a heterogeneous group of neuromuscular disorders all characterized by slowly progressive weakness in the shoulder-girdle and peroneal muscles. Both neurogenic and myopathic scapuloperoneal syndromes exist, the latter being referred to as scapuloperoneal myopathy (SPM). Distinct subtypes of SPM are caused by mutations in the sarcomeric muscle proteins desmin and myosin heavy chain 7. The X-linked dominant form of SPM (XSPM) is caused by mutations in the FHL1 gene.","Nervous system disease; Musculoskeletal disease"
"H02101","Autosomal dominant sensory ataxia","Autosomal dominant sensory ataxia (ADSA) is a rare genetic condition that results in a progressive ataxia. ADSA is suggested to be caused by degeneration of the posterior columns of the spinal cord. The mutation in the RNF170 gene causes ADSA.","Nervous system disease"
"H00232","Hereditary stomatocytosis","Hereditary stomatocytosis (HSt) describes a group of hemolytic anemias with mouth-shaped red blood cells which fail to transport monovalent cations, such as sodium and potassium.","Hematologic disease"
"H01314","Rat-bite fever","Rat-bite fever is a systemic febrile zoonotic illness caused by either Streptobacillus moniliformis, common in Western countries, or Spirillum minus, which is the most prevalent pathogen in Asia. It is manifested by acute relapsing fever with migratory polyarthralgia. It is transmitted from rodents to humans either by rodent urine or from mucosal secretions.","Infectious disease"
"H01126","Familial renal glucosuria","Familial renal glucosuria (FRG) is a rare autosomal recessive disorder of the kidney characterized by decreased renal tubular resorption of glucose from the urine in the absence of hyperglycemia and any other signs of tubular dysfunction. The vast majority of affected individuals are asymptomatic, but there is a rare propensity to develop hypoglycemia and hypovolemia. FRG is associated with mutations in the SGLT2 gene.","Urinary system disease; Inherited metabolic disease"
"H01542","Bolivian hemorrhagic fever","Bolivian hemorrhagic fever is an infectious disease caused by Machupo virus (MACV), a New World arenavirus in the Arenaviridae family of -ssRNA viruses, and transmitted by rodents. MACV was first isolated in 1963 in Bolivia.","Infectious disease"
"H00490","Diaphyseal dysplasia with anemia","Diaphyseal dysplasia with anemia (Ghosal) is characterized by increased bone density associated with myelophthisic anemia. Mutation in TBXAS1, which encodes thromboxane synthase, has been reported.","Musculoskeletal disease"
"H01770","Macular dystrophy","The inherited macular dystrophies are characterized by bilateral visual loss and the finding of generally symmetrical macular abnormalities visible either on ophthalmoscopy or on retinal angiographs.","Nervous system disease"
"H02155","Dyssegmental dysplasia","The dyssegmental dysplasia is a rare, autosomal recessive skeletal dysplasia with micromelia. There are two recognized types: the severe, lethal Silverman-Handmaker type (DDSH) and the milder Rolland-Desbuquois type. Individuals with DDSH also have a flat face, micrognathia, cleft palate and reduced joint mobility, and frequently have an encephalocele. DDSH is caused by a functional null mutation of perlecan gene (HSPG2).","Congenital malformation"
"H00602","Glucocorticoid-remediable aldosteronism (GRA)","Glucocorticoid-remediable aldosteronism (GRA), also known as familial hypoaldosteronism type I, is an autosomal dominant disease that causes hypertension, hypokalemia, decreased plasma renin activity and increased aldosterone levels. GRA is caused by a chimeric gene that links the 11 [beta]-hydroxylase promoter sequence to the aldosterone synthase gene's coding region. As a result, aldosterone is ectopically synthesized in the cortisol-secreting zona fasciculata of the adrenal gland under the control of adrenocorticotropin (ACTH). The high levels of mineralocorticoids activate the mineralocorticoid receptor (MR) and upregulate Na reabsorption and K secretion. Most individuals have severe hypertension since infancy but milder phenotypes have been described.","Endocrine disease"
"H00430","Fibrodysplasia ossificans progressiva","Fibrodysplasia ossificans progressiva (FOP) is a very rare disorder that leads to progressive ossification of muscle tissue and connective tissue. This process becomes noticeable in early childhood. Affected individuals harbor missense mutations in the ACVR1A gene that brings about constitutive activation of BMP type I receptor. FOP can be inherited in an autosomal dominant pattern.","Musculoskeletal disease"
"H02367","Chorea, childhood-onset, with psychomotor retardation","Chorea, childhood-onset, with psychomotor retardation (COCPMR) is a familial developmental disorder characterized by chorea, marked speech delay, and learning difficulties. Mutations in GPR88 are associated with COCPMR.","Nervous system disease"
"H00054","Nasopharyngeal cancer","Nasopharyngeal carcinoma (NPC) is a rare disease in most parts of the world, with an age-standardised annual incidence of less than 1 per 100000. However, in Southern China, parts of Southeast Asia and the Mediterranean basin, NPC is an endemic disease with an incidence of 10-30 per 100000. Genome-wide studies have unravelled multiple chromosomal abnormalities with involvement of specific oncogenes and tumor suppressor genes. Alterations of genes such as Ras association domain family 1A (RASSF1A), p16/INK4A, p14/ARF suggest that multiple cellular pathways were dysregulated in the NPC cells. Studies on the precancerous lesions revealed early genetic changes and a critical role of Epstein- Barr virus (EBV) latent infection in the development of this cancer.","Cancer"
"H01186","Abnormal thyroid hormone metabolism","Abnormal thyroid hormone metabolism is a disorder associated with an inherited selenocysteine (Sec) incorporation defect, caused by mutations in SECISBP2 (also called SBP2). Because SBP2 is epistatic to selenoprotein synthesis, these defects have a generalized effect on selenoproteins. Fibroblasts of affected patients show decreased deiodinase type 2 (DIO2) enzymatic activity not linked to the DIO2 locus.","Inherited metabolic disease"
"H00868","Stapes ankylosis with broad thumb and toes","This syndrome is characterized by conductive hearing loss due to congenital fixation of stapes, hyperopia, a hemicylindrical nose, broad thumbs and first toes. Noggin, the causative gene of several symphalangisms, has been implicated in the disease.","Congenital malformation"
"H00266","Hereditary spastic paraplegia","Hereditary spastic paraplegias (SPG) are a group of clinically and genetically diverse disorders characterized by progressive distal limb weakness and lower extremity spasticity.","Nervous system disease"
"H01172","Infantile ascending hereditary spastic paralysis","Infantile-onset ascending spastic paralysis (IAHSP) is a rare autosomal recessive early onset motor neuron disease caused by mutations in the gene ALS2. IAHSP is allelic to juvenile amyotrophic lateral sclerosis (JALS) [DS:H00058] and juvenile primary lateral sclerosis (JPLS) [DS:H00970]. IAHSP can be distinguished from those two disorders by the association of an infantile onset, at the age of walking achievement, with an ascending progression during childhood but a long survival during adulthood.","Nervous system disease"
"H00292","Hypertrophic cardiomyopathy","Hypertrophic cardiomyopathy (HCM) is a primary myocardial disorder with an autosomal dominant pattern of inheritance that is characterized by hypertrophy of the left ventricles with histological features of myocyte hypertrophy, myfibrillar disarray, and interstitial fibrosis. HCM is one of the most common inherited cardiac disorders, with a prevalence in young adults of 1 in 500. Hundreds of mutations in the genes that encode protein constituents of the sarcomere have been identified in HCM. These mutations increase the Ca2+ sensitivity of cardiac myofilaments. Increased myofilament Ca2+ sensitivity is expected to increase the ATP utilization by actomyosin at submaximal Ca2+ concentrations, which might cause an imbalance in energy supply and demand in the heart under severe stress. The inefficient use of ATP suggests that an inability to maintain normal ATP levels could be the central abnormality. This theory might be supported by the discovery of the role of a mutant PRKAG2 gene in HCM, which in active form acts as a central sensing mechanism protecting cells from depletion of ATP supplies. The increase in the myfilament Ca2+ sensitivity well account for the diastolic dysfunction of model animals as well as human patients of HCM. It has been widely proposed that left ventricular hypertrophy is not a primary manifestation but develops as compensatory response to sarcomere dysfunction.","Cardiovascular disease"
"H01340","Bethlem myopathy","Bethlem myopathy is one of the collagen VI myopathies, caused by mutation of COL6A. Bethlem myopathy is usually inherited in an autosomal dominant manner, but a rare autosomal recessive inheritance has recently been reported. This disease is characterized by a combination of proximal muscle weakness and contractures of finger, elbow, and ankle joints.","Nervous system disease; Musculoskeletal disease"
"H01724","HTLV1-associated myelopathy","Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic progressive myelopathy characterized by bilateral pyramidal tract involvement with sphincteric disturbances. HTLV-1 is the etiologic agent of HAM/TSP. Although the majority of HTLV-1-infected individuals remain asymptomatic during their lifetime, approximately one percent of this population develops a myelopathy consisting of a chronic inflammation of the white and gray matter of the spinal cord. Early in the disease process the leptomeninges, blood vessels and parenchyma are infiltrated with CD4+, CD8+, B lymphocytes and foamy macrophages, whereas later in the disease CD8+ lymphocytes predominate with subsequent progression to a relatively acellular, atrophic pattern with axonal and myelin degeneration.","Immune system disease; Nervous system disease"
"H01516","Adult onset Still disease","Adult-onset Still disease (AOSD) is a systemic inflammatory disorder. The disease manifestations are protean ranging from high fever, arthralgia, skin rash, sore throat, lymphadenopathy, and hepatosplenomegaly accompanied by systemic manifestations. Complications of AOSD include transient pulmonary hypertension, macrophage activation syndrome, diffuse alveolar hemorrhage, thrombotic thrombocytopenic purpura and amyloidosis. Common laboratory abnormalities include neutrophilic leukocytosis, abnormal liver function tests, and elevated acute-phase reactants (ESR, CRP, ferritin). The exact pathogenesis of AOSD is unknown. Several factors such as genetics, infectious (bacterial and viral) agents, and environmental factors have been thought to play a causative role. Although no familial trend has been reported in AOSD, some studies have reported an association between AOSD and gene polymorphism of HLA, IL-18, and MEFV. Recent advances have revealed a pivotal role of proinflammatory cytokines such as TNF-alpha, IL-1, IL-6, IL-8, and IL-18 in disease pathogenesis. Treatment consists of anti-inflammatory medications. Non-steroidal anti-inflammatory drugs have limited efficacy, and corticosteroid therapy and disease-modifying anti-rheumatic drugs are usually required.","Immune system disease"
"H02393","Talaromycosis","Talaromycosis (penicilliosis) is a life-threatening mycosis caused by the dimorphic fungus Talaromyces marneffei, which was first isolated from a bamboo rat in Vietnam in 1956. It affects primarily immunocompromised residents and travellers in southeast Asia, southern China, and northeastern India. It is a major cause of death in patients with advanced HIV infection in these areas. Infections probably occur through inhalation of T. marneffei conidia.","Infectious disease"
"H00259","Apparent mineralocorticoid excess syndrome","Apparent mineralocorticoid excess (AME) syndrome is characterized by hypertension, low plasma renin and aldosterone and hypokalaemia caused by deficiency of 11b-hydroxysteroid dehydrogenase type 2 which is a microsomal enzyme complex responsible for the interconversion of cortisol and cortisone.","Endocrine disease"
"H00857","Oligodontia-colorectal cancer syndrome","Oligodontia-colorectal cancer syndrome is a condition of dominant inheritance in which severe permanent tooth agenesis and a variable colorectal neoplasia occur. Affected individuals lack at least eight permanent teeth. The disease is caused by a nonsense mutation in AXIN2.","Mouth and dental disease"
"H01985","Desmoplastic small round cell tumor","Desmoplastic small round cell tumor (DSRCT) is a rare tumor typically involving peritoneum. The concept of DSRCT as a distinct tumor has been strengthened by association with a specific chromosomal abnormality, t(11;22)(pl3;q12) that involves the EWSR1 and WT1 genes. EWSR1 encodes the EWS protein which is a member of the FET family of RNA-binding proteins, while WT1 encodes a zinc-finger transcription factor. Several transcriptional targets of the EWSR1-WT1 chimera have been identified such as Platelet Derived Growth Factor A (PDGFA), IL2 receptor-beta, Myeloid Leukemia Factor 1 (MLF1) or Insulin-like Growth Factor 1 receptor (IGF1-R). Somatic MET and PIK3CA mutations have also been identified.","Cancer"
"H02358","Arthrogryposis multiplex congenita, neurogenic, with myelin defect","Arthrogryposis multiplex congenita, neurogenic, with myelin defect (AMCNMY) is caused by loss-of-function mutations in LGI4. LGI4 is a ligand secreted by Schwann cells that regulates peripheral nerve myelination via its cognate receptor ADAM22 expressed by neurons. The phenotypic spectrum of LGI4-related AMC varies from a most severe form with intrauterine onset resulting in utero death or termination to neonatal death to milder form with distal arthrogryposis, areflexia, developmental delay, and other variable features.","Nervous system disease"
"H01529","Avascular necrosis of femoral head","Avascular necrosis of the femoral head (ANFH) is one of the most common diseases of osteonecrosis that leads to destruction of the hip joint. Osteonecrosis is a pathological process in which cellular death in the bone constituents occurs because of decreased blood flow or an interruption in the blood supply. ANFH occurs mainly in young individuals between 30 and 50 years old. The clinical manifestations of ANFH, including pain on exertion, limping gait, and discrepancy in leg length, cause considerable disability. The etiology of ANFH is unknown, but previous studies have indicated that heritable thrombophilia and hypofibrinolysis, alcohol intake, and steroid use are risk factors for ANFH. Most cases are sporadic, but familial cases have been described. It has been reported Legg-Calve-Perthes disease (LCPD) is a particular type of femoral head necrosis occurring in children. It is more common among boys, and bilateral involvement occurs in 8-24% of cases. The disease is usually diagnosed among children under age 14 years, with a peak onset between 5 and 8 years of age. There is delayed skeletal maturation and impaired growth. In addition to congenital abnormalities, LCPD is associated with greater risk of cardiovascular diseases and diseases of the blood. Most cases are sporadic, but familial cases have been described. It has been reported that COL2A1 mutations are associated with this disease. Recent studies have suggested that an association exists between ANFH and genetic polymorphisms in the plasminogen activator inhibitor (SERPINE1), vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (NOS3), and P-glycoprotein (ABCB1) genes.","Musculoskeletal disease"
"H01971","IPEX syndrome","IPEX syndrome is a fatal disorder characterized by immune dysregulation, polyendocrinopathy, enteropathy and X-linked inheritance. This disease is caused by mutations in FOXP3, a critical regulator of T-cell homeostasis. Clinically, IPEX manifests most commonly with diarrhea, insulin-dependent diabetes mellitus, thyroid disorders, and eczema.","Primary immunodeficiency"
"H01511","Mast-cell leukemia","Mast cell leukemia (MCL), the leukemic manifestation of systemic mastocytosis (SM), is characterized by leukemic expansion of immature mast cells (MCs) in the bone marrow (BM) and other internal organs; and a poor prognosis. Gain-of-function mutations in the proto-oncogene c-kit that induce constitutive kinase activity of its product, KIT protein, are characteristic of various neoplastic diseases including MCL. Downstream signaling pathways, including PI3 kinase (PI3K)/AKT, are inappropriately activated, and this is believed to contribute to the abnormal proliferation and survival of these neoplastic cells. The reason why the prognosis of patients with MCL is mostly that MCs in these patients are largely resistant against conventional drugs and targeted drugs, including tyrosine kinase inhibitors (TKI) directed against KIT D816V such as PKC412 (midostaurin).","Cancer"
"H02394","Cleft palate, cardiac defects, and mental retardation","Cleft palate, cardiac defects, and mental retardation (CPCMR) is characterized by atrial or ventricular septal defects, cleft palate, and variable developmental delays and intellectual disability. It has been reported that deletions in MEIS2 can cause this disease. MEIS2 is a homeodomain-containing transcription factor of the TALE superfamily that has been proven important for development.","Congenital malformation"
"H01723","Deep vein thrombosis","Deep vein thrombosis (DVT) is the formation of blood clots (thrombi) in the deep veins. It can lead to complications such as postphlebitic syndrome, pulmonary embolism and death. DVT has genetic and acquired risk factors. The genetic risk factors can be subdivided into those that are strong, moderate and weak. Strong risk factors are deficiencies of antithrombin, protein C and protein S. Moderately strong are factor V Leiden, prothrombin 20210A, non-O blood group and fibrinogen 10034T. There are many weak genetic risk factors, including fibrinogen, factor XIII and factor XI variants. Acquired risk factors include surgery, oral contraceptives, trauma, obesity, cancer, and so on. In some patients, venous thrombosis occurs in the presence of such risk factors for DVT. These patients are classified as having secondary DVT. In the other patients, no predisposing factors are found, and thus, are considered as having an idiopathic DVT.","Hematologic disease"
"H00295","Viral myocarditis","Myocarditis is clinically defined as cardiac disease associated with inflammation of the myocardium and necrosis and/or degeneration of adjacent myocytes in the absence of an ischemic event. Most often, myocarditis results from common viral infections; less commonly, specific forms of myocarditis may result from other pathogens, toxic or hypersensitivity drug reactions, giant-cell myocarditis, or sarcoidosis. More than 20 common viruses, including coxsackieviruses, adenoviruses, influenza viruses, cytomegaloviruses, and human immunodeficiency virus, have been associated with myocarditis in humans. However, coxsackieviruses are considered the dominant cause of myocarditis, particularly in neonates and young children. After the acute phase caused by direct cytopathic effects of the virus, a small proportion of patients subsequently develop autoimmune- mediated, chronic myocarditis [4], accompanied by circulating autoantibodies to cardiac myosin and other heart antigens, which can sometimes lead to heart failure and death associated with dilated cardiomyopathy (DCM). Genetic linkage between susceptibility to myocarditis/DCM and the major histocompatibility complex (MHC) genes has been reported in both humans and experimentally induced mouse models.","Cardiovascular disease"
"H01347","MELAS Syndrome","MELAS Syndrome (Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes) is a maternally inherited multisystem mitochondrial disorder. This disease is associated with mutations in mitochondrial DNA and a biochemical deficiency of respiratory chain complex I. About 80% of MELAS patients have an A3243G mutation in the MTTL1 gene. Other mutations in MTTL1, other mitochondrial tRNA genes, and the mitochondrial MTND subunit genes of complex I have also been reported to cause MELAS.","Inherited metabolic disease; Mitochondrial disease"
"H01175","Staphylococcal infection","Staphylococci are widespread as commensals of humans and animals where they colonize the skin or mucous membranes. Firstly, Staphylococcus lugdunensis is a most unusual coagulase-negative staphylococcus found on the human skin. It can cause infections at many sites including superficial skin infections, bacteremia, endocarditis, osteomyelitis, and breast abscess. Endocarditis caused by S. lugdunensis can lead to substantial morbidity and mortality. Secondly, Staphylococcus haemolyticus, found among the normal skin flora, is commonly isolated from the axillae, perineum, and inguinal areas of humans and causes septicemia, peritonitis, otitis, and urinary tract infections. S. haemolyticus is notorious for its multidrug resistance and historically early acquisition of resistance to methicillin and glycopeptide antibiotics. Finally, Staphylococcus pseudintermedius is an important opportunistic pathogen of dogs and cats. S. pseudintermedius colonization is very uncommon in humans. It is rarely isolated from human dog-bite wounds. The infection has been associated with wide range of symptoms such as bacteremia, a brain abscess, and pneumonia.","Infectious disease"
"H01949","Glycogen storage disease type 0b","Glycogen storage disease type 0b (GSD-0b), also known as muscle glycogen synthase deficiency, is an autosomal recessive disorder of glycogen metabolism. GSD-0b is caused by mutations in the GYS1 gene, which encodes muscle glycogen synthase. The role of muscle and heart glycogen is to provide critical energy during bursts of activity and sustained muscle work. It has been reported that patients showed muscle fatigability, hypertrophic cardiomyopathy, and an abnormal heart rate and blood pressure while exercising.","Inherited metabolic disease"
"H00261","Meckel syndrome","Meckel syndrome (MKS) is a lethal, autosomal recessive disorder characterized by anomalies of the central nervous system, cystic dysplasia of the kidneys, and malformations of the hands and feet.","Congenital malformation"
"H00053","Extraskeletal myxoid chondrosarcoma","Extraskeletal myxoid chondrosarcoma (EMC) is a unique, rare soft-tissue tumor with prominent myxoid morphology. The tumor most commonly develops in deep parts of the proximal extremities and limb girdles in middle-aged adults, and there is a predilection for male patients. Currently, a chromosomal translocation t(9;22)(q22;q12) and the resultant fusion gene, EWSR1-NR4A3, has been defined in approximately 75% of EMC. More recently, another fusion gene, TAF15-NR4A3, resulting from t(9;17)(q22;q11.2), has been identified. The abnormal proteins resulting from these fusion genes aberrantly affect gene transcription and cellular signaling pathways thought to be responsible for initiating sarcoma formation.","Cancer"
"H01181","T-cell immunodeficiency congenital alopecia and nail dystrophy","T-cell immunodeficiency congenital alopecia and nail dystrophy (TIDAND) is a severe combined immunodeficiency (SCID) syndrome caused by a mutation in FOXN1 gene encoding the forkhead/winged helix (WHN) FOXN1 transcription factor selectively expressed in thymic epithelia and skin. SCIDs are disorders of both cell-mediated and humoral immunity, characterized by high susceptibility to develop severe and sometimes fatal infections. TIDAND is the only human SCID caused by an intrinsic abnormality of the epithelial component of the thymus. The disease is always associated with a profound T-cell defect.","Immune system disease"
"H00437","Paget disease of bone","Paget disease of bone are rare inherited osteolytic disorders that show phenotypic overlap. Patients with these diseases carry mutations in RANK/TNFRSF11A, OPG/TNFRSF11B or SQSTM1, resulting in activation of RANKL-RANK signaling axis with increases in bone resorption. Hearing impairment and tooth loss is common. Apart from juvenile-onset Paget's disease (PDB5), the condition is inherited as an autosomal dominant trait.","Musculoskeletal disease"
"H02360","Epileptic encephalopathy, childhood-onset","Epileptic encephalopathy, childhood-onset (EEOC) is CHD2-related neurodevelopmental disorder, inherited in an autosomal dominant manner. It is characterized by refractory seizures and cognitive slowing or regression associated with frequent ongoing epileptiform activity. Intellectual disability and/or autism spectrum disorders are common.","Nervous system disease"
"H02152","Transient familial neonatal hyperbilirubinemia","Transient familial neonatal hyperbilirubinemia, also known as Lucey-Driscoll syndrome, is a rare familial disorder that causes severe unconjugated hyperbilirubinemia in the first few days of life. It has been suggested that mutations in UGT1A1 cause this disease.","Congenital disorder of metabolism"
"H00605","Deafness, autosomal recessive","Hereditary deafness is divided into syndromic forms (in which hearing loss is associated with a variety of other anomalies) and non-syndromic forms. Non-syndromic forms are responsible for 70% of the cases of hereditary etiology and syndromic cases represent 30% of them. Among the forms of heritage, autosomal-recessive inheritance is the most frequent one (75%-85%), followed by autosomal- dominant inheritance (12-13%) and X-linked or mitochondrial, with 2-3% of the cases of non-syndromic hearing loss. The autosomal-recessive forms of deafness are generally the most severe and are almost exclusively caused by cochlear defects (sensorineural deafness), in contrast to the syndromic forms of deafness, where the hearing loss in most cases is conductive (external and/or middle ear developmental defects) or mixed.","Nervous system disease"
"H00098","Chronic granulomatous disease","Chronic granulomatous disease (CGD) is characterized by impaired activation of the NADPH oxidase activity in phagocytic cells, resulting in the inability of these cells to generate toxic oxygen radicals and hence to kill catalase-positive bacteria. The NADPH oxidase is composed of four polypeptide subunits and mutations in the corresponding genes (gp91phox, p22phox, p47phox, and p67phox) are responsible for the four different genetic subgroups of CGD. Most cases (65%) involve mutations in gp91phox and are inherited in an X-linked recessive manner. The remainder are autosomal recessive (AR).","Primary immunodeficiency"
"H01976","Tibial muscular dystrophy","Tibial muscular dystrophy (TMD) is a rare autosomal dominant distal myopathy with late onset. The clinical phenotype is relatively mild. Muscle weakness manifests in the patient's early 40s and remains confined to the tibial anterior muscles. TMD is caused by mutations in TTN, the gene encoding the giant skeletal-muscle protein titin.","Nervous system disease; Musculoskeletal disease"
"H01378","Bosch-Boonstra optic atrophy syndrome","Bosch-Boonstra optic atrophy syndrome is an autosomal dominant disorder characterized by mild to moderate intellectual impairment and optic atrophy. Heterozygous mutations in the NR2F1 gene have been associated with this disease.","Nervous system disease"
"H02199","Congenital heart defects, multiple type","Congenital heart defects (CHTD) are the most common major developmental anomalies and the most frequent cause for perinatal mortality, but their etiology remains often obscure. It is generally understood that abnormal cardiovascular development during embryogenesis may be attributed to an aberrant biological process that is heterogeneous and complex, with both environmental and genetic risk factors involved.","Congenital malformation"
"H00408","Type 1 diabetes mellitus","The majority of type 1 diabetes mellitus (T1DM) cases are believed to arise from an inflammatory, autoimmune attack against the beta cells in the pancreas, which consequently leads to the failure of insulin-mediated blood glucose regulation in the body. T1DM signs and symptoms can come on quickly and may include increased thirst and frequent urination, fatigue, weight loss and so on. It is recognized that both genetic and environmental determinants are important in defining disease risk. The HLA class II genes are most strongly associated with T1DM. Another plausible candidate genes are INS, CTLA4 and PTPN22. The disease may be a result of variations in several susceptibility genes, with the majority only contributing weak effects.","Metabolic disease; Immune system disease; Endocrine disease"
"H00850","Frontorhiny","Frontorhiny, also known as median facial cleft syndrome, is a recently characterized autosomal recessive frontonasal malformation with hypertelorism, abnormal nasal configuration, and cleft lip. This disorder is caused by disturbed developmental sequence between 4 and 8 weeks in which formation of the face takes place.","Congenital malformation"
"H01982","Carnitine palmitoyltransferase II deficiency","Carnitine palmitoyltransferase II (CPT2) deficiency is an inherited disorder of mitochondrial long-chain fatty-acid oxidation. Three distinct clinical manifestations of CPT2 deficiency have been defined including a mild adult onset myopathy, a severe infantile disorder and a lethal neonatal form.","Inherited metabolic disease; Mitochondrial disease"
"H01371","Hypercalcemia infantile","Idiopathic infantile hypercalcemia is autosomal recessive disorder that is characterized by severe hypercalcemia, failure to thrive, vomiting, dehydration, and nephrocalcinosis. It has been reported that mutations in the vitamin D-metabolizing enzyme CYP24A1 cause this disease. The presence of CYP24A1 mutations explains the increased sensitivity to vitamin D in patients with idiopathic infantile hypercalcemia.","Congenital disorder of metabolism"
"H01143","Vitamin D-dependent rickets","Rickets is the failure of growing bone to mineralize. Many skeletal and radiographic changes can occur because of the lack of calcified osteoid and the buildup of unossified cartilage. Vitamin D-dependent rickets type I results from abnormalities in the gene coding for 25(OH)D3-1-alpha-hydroxylase and vitamin D 25-hydroxylase, and type II results from defective vitamin D receptors. Both diseases are rare autosomal recessive disorders characterized by hypocalcemia, secondary hyperparathyroidism and early onset severe rickets.","Musculoskeletal disease; Inherited metabolic disease"
"H00091","T-B+Severe combined immunodeficiency","Severe combined immunodeficiency (SCID) comprises a heterogeneous group of monogenic disorders that result in early-onset severe infections by a range of pathogens (such as bacteria, viruses and fungi). Typically, patients with SCID have a severe defect in T-cell differentiation, along with direct or indirect impairment of B-cell development and function. SCIDs with lack of circulating T cells but a normal number of B cells accounts for 30 to 50% of all cases of human SCIDs. The most frequent form of SCID, X-linked SCID (SCID-X1), is caused by mutations in the gamma-chain-encoding gene. Gamma-chain is a common subunit shared by several cytokine receptors. It results in an absence of both mature T lymphocytes and NK lymphocytes. The second most common variant is autosomal recessive and due to mutations of the JAK3 gene. IL-7R alpha gene mutations result in a pure T-cell deficiency. Rare cases of SCID consisting of pure T-cell deficiencies have been attributed to defects in key proteins involved in pre-TCR/TCR signaling. Deficiency in the CD45 phosphatase has been reported in two cases of SCID, while defects in CD3 delta, CD3 epsilon and CD zeta have also been described.","Primary immunodeficiency"
"H01527","Chronic inflammatory demyelinating polyradiculoneuropathy","Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a polyneuropathy that is often disabling, with more than 50% of patients reported as having temporary disability, and about 10% eventually becoming persistently disabled. The core clinical features are a chronic progressive or relapsing and remitting, symmetrical, and sensory and motor polyradiculoneuropathy causing weakness of proximal and distal muscles. The etiology is suspected to be of autoimmune origin, and the diagnosis is typically based on clinical history, neurologic examination, electrophysiologic studies, cerebrospinal fluid (CSF) studies, and pathologic examination. CIDP often responds to immune therapies including corticosteroids, plasma exchange, and high-dose intravenous immunoglobulin (IVIg).","Immune system disease; Nervous system disease"
"H01715","Obesity hypoventilation syndrome","Obesity hypoventilation syndrome (OHS) is defined as the triad of obesity (BMI of 30 or higher), daytime hypoventilation, and sleep-disordered breathing in the absence of any other cause of hypoventilation. The features include marked obesity, somnolence, twitching, cyanosis, periodic respiration, polycythemia, and right ventricular hypertrophy and failure. Patients with untreated OHS have a significant risk of death. While continuous positive airway pressure (CPAP) treatments may temporize cardiopulmonary disease progression, simultaneous pursuit of weight reduction is central to long-term management of this condition.","Respiratory disease"
"H02190","CBL syndrome","CBL is a ubiquitously expressed E3 ubiquitin ligase that negatively regulates intracellular signalling downstream of receptor tyrosine kinases. Missense CBL mutations cause impaired growth, developmental delay, and cryptorchidism resembling Noonan syndrome. In addition, patients have distinctive facial features, cardiovascular malformation, cerebellar vermis hypoplasia, and predisposition to juvenile myelomonocytic leukaemia.","Congenital malformation"
"H02356","PCWH syndrome","PCWH syndrome (Peripheral demyelinating neuropathy, Central dysmyelination, Waardenburg syndrome, and Hirschsprung disease) is a rare inherited disorder caused by SOX10 mutations. SOX10 regulates the development and maintenance of neural crest derivatives including Schwann cells, melanocytes, and enteric ganglion cells, and of oligodendrocytes, which are not derived from the neural crest. Accordingly, SOX10 gene mutations result in a wide spectrum of clinical phenotypes involving these cells. It is suggested that the complex neurological phenotypes in PCWH patients likely result from a combination of haploinsufficiency and additive dominant effect.","Nervous system disease"
"H00401","Respiratory syncytial virus infection","Respiratory syncytial virus (RSV) of the Paramyxoviridae family is a major cause of acute lower respiratory tract illness in infants and young children. It affects the elderly and immunocompromised individuals as well. Although RSV was discovered half a century ago, no effective treatment for the infection exists.","Infectious disease"
"H00633","Duane retraction syndrome","Duane retraction syndrome (DRS) is a congenital disorder of eye movement that occurs in approximately 1 in 50 patients with strabismus. This condition prevents horizontal eye movement, with absence of outward movement and deficiency of inward movement. Normal ocular motility depends on precise relations between cranial motor neurons and their target, extraocular muscles. In DRS parients, absence of the abducens motor neurons and aberrant innervations of extraocular muscles by third cranial nerve have been reported.","Nervous system disease"
"H02164","Sandfly fever","Sandfly fever is an infectious disease caused by Sandfly fever Naples virus (SFNV), a phlebovirus in the order Bunyavirales of -ssRNA viruses, and transmitted by biting midges and mosquitoes. SFNV was first isolated in 1943 in Italy.","Infectious disease"
"H01385","Rienhoff syndrome","Rienhoff syndrome is a congenital syndrome presenting at birth with distal arthrogryposis, hypotonia, bifid uvula, and a failure of normal post-natal muscle development but no evidence of vascular disease. A mutation in TGFB3 was identified suggesting that decreased TGF-beta signaling from a loss of TGFB3 activity is likely responsible for the clinical phenotype.","Congenital malformation"
"H00257","Achalasia Addisonianism Alacrima syndrome","Achalasia-Addisonianism-Alacrima (AAA) syndrome, also known as triple-A syndrome, is a rare autosomal recessive disorder characterized by alacrima, achalasia, adrenal insufficiency and autonomic instability caused by mutation in the AAAS gene on 12q13. Recently, it has been reported that mutations in GMPPA cause alacrima, achalasia, and mental retardation syndrome (AAMR), that shows similarity to the triple A syndrome.","Endocrine disease"
"H02500","Congenital interstitial lung disease with nephrotic syndrome and epidermolysis bullosa","Congenital interstitial lung disease with nephrotic syndrome and epidermolysis bullosa (ILNEB) is a multiorgan disorder caused by mutations in ITGA3. ITGA3 encodes a transmembrane integrin receptor subunit that mediates signals between the cells and their microenvironment. Mutations in ITGA3 are associated with disrupted basement-membrane structures and compromised barrier functions in kidney, lung, and skin.","Congenital malformation"
"H00065","Alexander disease","Alexander disease is a rare, but often fatal neurological disorder that has been divided into three subtypes based on the age of onset: the infantile, juvenile and adult forms. The characteristic neuropathological feature of all forms of Alexander's disease is the presence of Rosenthal fibers which include protein aggregates that contain glial fibrillary acidic protein (GFAP) and small stress proteins in astrocytes.","Neurodegenerative disease"
"H00859","Guttmacher syndrome","Guttmacher syndrome is a disorder of distal limb and genital tract that resembles hand-foot-genital syndrome (HFGS). In addition to the typical features of HFGS, namely the combination of hypoplastic thumbs and halluces, 5th finger clinobrachydactyly and hypospadias, Guttmacher syndrome displays postaxial polydactyly of the hands and short or uniphalangeal 2nd toes with absent nails.","Congenital malformation"
"H01518","Lobomycosis","Lobomycosis, also known as Lobo disease or lacaziosis, is a chronic, granulomatous and cutaneous-subcutaneous infection that primarily occurs in tropical climates of Latin America. It is a zoonotic disease in humans and some species of dolphins. Main etiological agent is Lacazia loboi, a uncultivable dimorphic onygenale fungi.","Infectious disease"
"H01940","Glycogen storage disease type II","Glycogen storage disease type II (GSDII), also known as Pompe disease, is an autosomal recessive lysosomal storage disease caused by a deficiency of acid alpha-glucosidase (GAA). This deficiency results in glycogen accumulation in the lysosomes, leading to lysosomal swelling, cellular damage and organ dysfunction.","Congenital disorder of metabolism"
"H00892","Bronchiectasis with or without elevated sweat chloride","Bronchiectasis is a condition in which the airways are permanently dilated due to recurrent inflammation or infection. In many cases, the cause is unknown but recently some of the patients have been shown to have mutations in the epithelial sodium channel ENaC. Furthermore, a three-fold significant increase in incidence of several rare ENaC polymorphisms was found in the patients.","Respiratory disease"
"H01188","Tn syndrome","Tn syndrome is a rare autoimmune disease characterized by the expression of the Tn antigen, an incompletely glycosylated membrane glycoprotein, on all blood cell lineages. The epitope of the Tn antigen is terminal alpha-N-acetylgalactosamine alpha-linked to either a serine or threonine amino-acid residue. The defect may be due to a malfunction of the glycosylating enzyme T-synthase. Tn syndrome is associated with a somatic mutation in Cosmc gene, encoding a molecular chaperone that is required for the proper folding and hence full activity of T-synthase.","Hematologic disease"
"H00866","Trichothiodystrophy","Trichothiodystrophy (TTD) is a premature aging syndrome, with the hallmark feature of brittle hair and nails, ichthyosis, and progressive mental and physical retardation. Within photo-sensitive TTD, three TFIIH coding genes (ERCC2, ERCC3, and TTDA/GTF2H5) are implicated. Non-photosensitive trichothiodystrophy (TTDN) is characterized by short stature, intellectual impairment, sulfur-deficient brittle hair, and decreased male fertility but not cutaneous photosensitivity. Mutations in MPLKIP, RNF113A, and GTF2E2 have been reported.","Skin disease"
"H00268","Lissencephaly","Lissencephaly (LIS), literally meaning smooth brain, is a severe neuronal migration disorder that ranges from agyria/pachygyria to subcortical band heterotopia.","Congenital malformation"
"H02369","IMAGE-I syndrome","IMAGE-I syndrome is a rare autosomal recessive disorder characterized by intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, genital anomalies, and immunodeficiency. It has been reported that mutations in POLE cause IMAGE-I. POLE encodes the catalytic subunit of DNA polymerase epsilon.","Congenital malformation"
"H00062","Spinal and bulbar muscular atrophy (SBMA)","Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy disease, is a motor neuron disease characterized by progressive weakening of the limb and bulbar muscles. It is an X-linked recessive disease that only affects males. SBMA is caused by expansion of CAG trinucleotide repeats in the first exon of the androgen receptor gene. The expansion of encoded polyglutamine tracts results in protein aggregation and is associated with neuronal cell death.","Neurodegenerative disease"
"H01382","Polyarteritis nodosa","Polyarteritis nodosa is a systemic necrotizing vasculitis that affects medium and small muscular arteries. The ensuing tissue ischemia can affect any organ, including the skin, musculoskeletal system, kidneys, gastrointestinal tract, and the cardiovascular and nervous systems. In most cases, onset of the disease occurred during childhood. Polyarteritis nodosa is most often primary. Recessive mutations in the adenosine deaminase 2 (ADA2)-encoding gene CECR1 have been found from patients of this disease.","Vascular disease"
"H00250","Congenital nongoitrous hypothyroidism (CHNG)","Congenital nongoitrous hypothyroidism (CHNG) is characterized as resistance to thyroid-stimulating hormone (TSH) causing increased levels of plasma TSH and low levels of thyroid hormone which is essential for early brain development. The neonatal screening can avoid the poor prognosis of hypothyroidism.","Endocrine disease"
"H00634","Duane-radial ray syndrome","Duane-radial ray syndrome alias Okihiro syndrome is an autosomal dominant condition characterized by an association of Duane retraction syndrome (eye retraction) with radial malformations of the upper extremities and deafness. Mutations in the transcription factor SALL4 are the cause of the disorder.","Congenital malformation"
"H02163","Oropouche fever","Oropouche fever is an infectious disease caused by Oropouche virus (OROV), an orthobunyavirus in the order Bunyavirales of -ssRNA viruses, and transmitted by mosquitoes and biting midges. OROV was first isolated in 1955 in Trinidad and Tobago.","Infectious disease"
"H02351","Cowpox","Human cowpox is a rare zoonotic infectious disease caused by cowpox virus (CPXV), an orthopoxvirus in the Poxviridae family of dsDNA viruses. CPXV can infect a broad range of hosts. Natural reservoir hosts of CPXV are wild rodents. Transmission to humans is through contact with infected animals, mostly domestic cats, which are predators of wild rodents.","Infectious disease"
"H00406","Acquired immunodeficiency syndrome (AIDS)","Since the discovery in 1980s, HIV/AIDS has become the most important infectious disease globally. Many of the clinical features of HIV/AIDS can be ascribed to the profound immune deficiency in patients. HIV infection also increases the risk of autoimmune diseases and malignancies such as non-Hodgkin's lymphoma and Kaposi's sarcoma.","Infectious disease; Immune system disease"
"H01712","Fulminant hepatic failure","Fulminant hepatic failure (FHF) is a life-threatening condition characterized by the rapid deterioration of liver functions and hepatic encephalopathy. FHF is with the basic definition of the onset of hepatic encephalopathy within 8 weeks of the appearance of the first symptoms like jaundice, fever, nausea, and vomiting. The prothrombin time is prolonged by 4-6 seconds or more. While the etiologies of FHF are multiple and varied, viral hepatitis is the most frequent cause. Around 40-60% of patients with FHF are thought to be due to some viral infection. The prognosis is dependent on several factors, including the underlying cause of liver failure. For instance, it is well known that the spontaneous recovery rates from FHF from such etiologies as hepatitis A and acetaminophen toxicity are high, whereas those same rates for other types of viral hepatitis and idiosyncratic drug reactions are quite low. Identification of the cause of FHF is important because some causes have specific treatment interventions or antidotes. Specific therapies include N-acetylcysteine for acetaminophen overdose, and acyclovir for herpesvirus infection. Different therapeutic options such as complete exchange blood transfusion, corticosteroids, and plasma pheresis, have been tried. However, the overall prognosis for patients with FHF is quite poor, with survival rates usually reported between 10% and 30% without liver transplantation.","Liver disease"
"H02197","Mitochondrial pyruvate carrier deficiency","Mitochondrial pyruvate carrier deficiency is an autosomal recessive metabolic disorder characterized by delayed psychomotor development. Patients present with severe lactic acidosis, normal lactate/pyruvate ratios and normal pyruvate dehydrogenase activity. Mitochondrial pyruvate carrier mediates the proton symport of pyruvate across the inner mitochondrial membrane, and plays a key role in glycolysis and gluconeogenesis.","Congenital disorder of metabolism"
"H01520","Chromomycosis","Chromomycosis, also known as Chromoblastomycosis, is a chronic fungal infection of the skin and the subcutaneous tissue caused by a transcutaneous traumatic inoculation of a specific group of dematiaceous fungi usually found in tropical and subtropical areas. Main etiological agents belong to Fonsecaea and Cladophialophora genus and, while scattered cases have been reported in Phialophora, Rhinocladiella and Exophiala genus.","Infectious disease"
"H01144","Ochrobactrum anthropi infection","Ochrobactrum anthropi is an ubiquitous oxidase-producing gram-negative bacillus. The pathogen is recognized increasingly as a causative agent of central catheter-related infections, causing bloodstream infection in patients on hemodialysis.","Infectious disease"
"H00096","Defects of toll-like receptor signaling","Human interleukin (IL) 1 receptor-associated kinase 4 (IRAK-4) deficiency is a recently discovered primary immunodeficiency that impairs Toll/IL-1R immunity, except for the Toll-like receptor (TLR) 3- and TLR4-interferon (IFN)-a/b pathways. IRAK-4 is a kinase that plays a crucial role downstream of individual TLR and IL-1R receptors and upstream of TNF receptor-associated factor-6 (TRAF-6). Patients with IRAK-4 deficiency thus fail to produce TNF-alpha, IL-6, and IFN-gamma in response to IL-1beta and IL-18, respectively. Their blood cells also fail to produce IL-1beta, IL-6, IL-8, IL-12, and TNF-alpha upon stimulation with known TLR agonists. Despite the broad impairment at the two subsequent levels of onset (TLR) and propagation (IL-1R) of inflammation, the clinical phenotype of IRAK-4 deficiency is relatively mild. Patients present no developmental defect and a restricted spectrum of infectious diseases, mostly caused by pyogenic encapsulated bacteria, principally, but not exclusively Gram-positive.","Primary immunodeficiency"
"H01978","Dehydrated hereditary stomatocytosis","Dehydrated hereditary stomatocytosis (DHS), also known as hereditary xerocytosis, is an autosomal dominant congenital disorder associated with erythrocyte dehydration clinically manifest as mild to moderate hemolytic anemia. Affected red cells are characterized by a nonspecific cation leak of the red cell membrane, reflected in elevated sodium content, decreased potassium content, elevated mean corpuscular hemoglobin concentration (MCHC) and mean corpuscular volume (MCV), and decreased osmotic fragility. The definitive diagnosis of DHS is made by osmotic gradient ektacytometry, which shows a leftward shift of the bell-shaped curve. In many patients, heterozygous mutations in the mechanosensitive cation channel gene PIEZO1 have been identified. Mutations in the Gardos channel, encoded by the KCNN4 gene, have also been identified.","Cardiovascular disease"
"H01376","Acrofacial dysostosis","Acrofacial dysostosis (AFD) is a heterogeneous group of disorders combining mandibulofacial dysostosis (micrognathia and ear anomalies) with limb defects. The predominantly preaxial form is called Nager AFD, the predominantly postaxial form of AFD (POADS) is also known as the Genee-Wiedemann or Miller syndrome. Among several AFDs, causative mutations have recently been identified in an enzyme involved in pyrimidine biosynthesis in association with Miller syndrome, and in a component of the pre-mRNA spliceosomal complex with respect to Nager syndrome.","Congenital malformation"
"H00439","Shwachman-Diamond syndrome","Shwachman-Diamond syndrome (SDS) is a rare autosomal recessive disease, mainly characterized by exocrine pancreatic insufficiency, hematological dysfunction and skeletal abnormalities. In most cases, SDS is associated with mutations in SBDS, a protein involved in maturation and export of the ribosomal 60S subunit.","Ribosomopathy"
"H00861","Pancreatic agenesis","Pancreatic agenesis is a rare disorder resulted from a failure of the pancreas to develop. It can be associated with the severe form of permanent neonatal diabetes mellitus. Mutations in insulin promoter factor 1 (IPF1), an essential factor for pancreas development, decrease the protein level and lead to the disease.","Pancreas disease"
"H01349","Methacrylic aciduria","Methacrylic aciduria is a very rare cerebral organic aciduria caused by 3-Hydroxy-isobutyryl-CoA hydrolase (HIBCH) mutations. HIBCH is a mitochondrial enzyme of valine catabolism. Patients demonstrated delayed development of motor skills, hypotonia, initial poor feeding, and a deterioration in neurological function during the first stages of life.","Inherited metabolic disease; Mitochondrial disease"
"H01947","Fanconi-Bickel syndrome","Fanconi-Bickel syndrome (FBS) is a rare autosomal recessive disorder of carbohydrate metabolism. FBS is caused by mutations in the SLC2A2 (GLUT2) gene, which encodes the glucose transporter. The typical clinical signs are hepatomegaly secondary to glycogen accumulation, glucose and galactose intolerance, fasting hypoglycemia, a characteristic tubular nephropathy, rickets, and markedly stunted growth.","Inherited metabolic disease"
"H00895","Basal cell nevus syndrome","Basal cell nevus syndrome is a rare autosomal dominant disorder that predisposes to tumor formation especially basal cell carcinomas associated with developmental abnormalities such as odontogenic keratocyst of the mandible, calcification of the falx cerebri, multiple nevi, and skeletal anomalies. The genetic basis of the syndrome is defective hedgehog signaling pathway.","Skin and connective tissue disease"
"H01118","Progressive external ophthalmoplegia","Progressive external ophthalmoplegia (PEO) is a a progressive weakness of the external muscles of the eye resulting in blepharoptosis and ophthalmoparesis. Often other muscles are involved resulting in dysphagia and a variable neck and limb muscle weakness. Most sporadic PEO cases have an acquired genetic disease with a heteroplasmic large deletion of mitochondrial DNA (mtDNA) in muscle. In familial PEO, several modes of inheritance occur. Patients may have a nuclear gene defect that predisposes to the accumulation of mtDNA deletions. Recently, mutations in such nuclear genes have been discovered. Some mutations are dominant (PEOA) and others recessive.","Nervous system disease; Congenital disorder of metabolism"
"H01924","Sydenham chorea","Sydenham chorea is a disabling pediatric hyperkinetic and neuropsychiatric disorder following streptococcal infection. Sydenham chorea occurs in approximately 10% of acute rheumatic fever and is one of its major manifestations. The disease may last for weeks or months, with a high risk of recurrence. The common features of rheumatic fever include sore throats due to streptococcal infections, rashes, pains in the limbs, and subcutaneous nodules, and this form of chorea typically presents, after varying intervals, with twitching of the mouth and limbs, shrugging of the shoulders, and clumsy gait. Those with this form of chorea are less likely to have severe cardiac or rheumatologic complications. The pathogenesis has been considered to be an autoantibody-mediated basal ganglia dysfunction. Anti-inflammatory treatments such as steroids, plasmapheresis and intravenous immunoglobulin treatment are effective.","Immune system disease; Nervous system disease"
"H00802","Ehlers-Danlos syndrome","Ehlers-Danlos syndrome (EDS) is an inherited heterogeneous group of connective tissue disorders, characterized by abnormal collagen synthesis, affecting skin, ligaments, joints, blood vessels and other organs. Most EDS subtypes are caused by mutations in genes encoding the fibrillar collagens, or in genes coding for enzymes involved in the post-translational modification of these collagens. EDS can be classified into 13 subtypes: classical type (EDSCL), classical-like type (EDSCLL), cardiac-valvular type (EDSCV), vascular type (EDSVASC), hypermobility type (EDSHMB), arthrochalasia type (EDSARTH), dermatospraxis type (EDSDERMS), kyphoscoliosis type (EDSKSCL), brittle cornea syndrome (BCS), spondylodysplastic type (EDSSPD), musculocontractural type (EDSMC), myopathic type (EDSMYP), and periodontal type (EDSPD).","Congenital malformation"
"H01588","Cluster headache","Cluster headache (CH) is the commonest of the trigeminal autonomic cephalalgias (TAC) characterized by attacks of severe, strictly unilateral pain, which is orbital, supraorbital, temporal, or in any combination of these sites, with duration of pain attacks of 15 to 180 min. The pain of CH is associated with ipsilateral conjunctival injection, lacrimation, nasal congestion, rhinorrhea, forehead and facial sweating, miosis, ptosis and/or eyelid edema, and/or restlessness or agitation. Headaches often recur at the same time each day during the cluster period, which can last for weeks to months. CH occurs more commonly in male patients (2.5:1 to 4.3:1 male to female) with an average age of onset in the third or fourth decade. The pathophysiology of CH is not fully understood, but may include a genetic component. Treatment focuses on avoiding triggers and includes abortive therapies, prophylaxis during the cluster period, and long-term treatment in patients with chronic CH. Evidence supports the use of supplemental oxygen, sumatriptan, and zolmitriptan for acute treatment of episodic CH. Verapamil is used to treat chronic CH. More invasive treatments, including nerve stimulation and surgery, may be helpful in refractory cases.","Nervous system disease"
"H00668","Anemia due to disorders of glutathione metabolism","Anemia due to disorders of glutathione metabolism is a group of red cell disorders caused by inherited abnormality of enzymes of glutathione metabolism. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymatic disorder of red blood cells in humans. It is estimated that about 400 million people are affected by this deficiency. A G6PD-deficient patient lacks the ability to protect red blood cells against oxidative stresses from certain drugs, infections, metabolic conditions, and ingestion of fava beans. GCLC catalyzes the initial and the rate-limiting step of glutathione synthesis. Deficiency of GCLC is extremely rare. GSS deficiency is a more frequent cause of glutathione deficiency.","Inherited metabolic disease; Hematologic disease"
"H01127","PIGM-congenital disorder of glycosylation","PIGM-congenital disorder of glycosylation (PIGM-CDG) is an autosomal recessive disorder characterized by portal- and hepatic-vein thrombosis and epilepsy. Hypomorphic promoter mutation in PIGN causes this disorder.","Inherited metabolic disease"
"H01315","Erysipeloid","Erysipelothrix rhusiopathiae is a non-sporulating, gram-positive, rod-shaped bacterium which was identified as the etiologic agent of swine erysipelas. Infection in man is occupationally related, occurring principally as a result of contact with animals, and mainly found in animal breeders, veterinarians, slaughterhouse workers, and other occupations. Non-occupational cases are very rare. Three forms of human disease have been recognized, including a mild cutaneous infection known as erysipeloid, a diffuse cutaneous form, and a serious although rare systemic complication with septicemia and endocarditis.","Infectious disease"
"H01771","Congenital ichthyosis","The ichthyoses represent a large group of cutaneous disorders linked by the common finding of abnormal epidermal differentiation. These disorders are characterized by the cutaneous scaling, which is said to resemble the scales of a fish. Scaling can be localized or generalized and can be associated with a variety of additional cutaneous and/or systemic manifestations. In patients with ichthyosis, the barrier function of the skin is compromised and has a decreased ability to protect against bacterial or chemical assault and to prevent transepidermal water loss. Ichthyosis vulgaris (H00735) is the most frequent type. X-linked ichthyosis (H00134) occurs almost exclusively in boys. Autosomal recessive congenital ichthyosis (H00734) is genetically very heterogeneous and several different genes have been identified. Mutations in keratin genes are the cause of the keratinopathic ichthyoses (H00691), such as epidermolytic ichthyosis.","Congenital malformation"
"H01543","Venezuelan hemorrhagic fever","Venezuelan hemorrhagic fever is an infectious disease caused by Guanarito virus (GTOV), a New World arenavirus in the Arenaviridae family of -ssRNA viruses, and transmitted by rodents. GTOV was first isolated in 1989 in Venezuela.","Infectious disease"
"H00491","Craniometaphyseal dysplasia","Craniometaphyseal dysplasia, caused by mutations in ANKH, is a very rare condition characterized by progressive hyperostosis of cranial bones and malformations of metaphyseal long bones.","Congenital malformation"
"H01785","Tricuspid atresia","Tricuspid atresia is the third most common cyanotic congenital heart defect. It consists of complete lack of tricuspid valve formation, with no connection between the right atrium and the right ventricle. Severe cyanosis associated with diminished pulmonary blood flow is a prominent feature in tricuspid atresia. The malformation brings about high morbidity and mortality, thus requiring the utilization of an adequate surgical technique for its correction. The genetic mechanism responsible of tricuspid atresia is still obscure. However, animal models have suggested a role of cardiogenic Zfpm2/Fog2 and Hey2 genes in the pathogenesis.","Developmental disorder; Cardiovascular disease"
"H00657","Reducing body myopathy","Reducing body myopathy (RBM) is a rare, sometimes fatal, X-linked disorder characterized by progressive muscle weakness and the presence of intracytoplasmic aggregates in histological muscle sections which exert a reducing activity on nitro-blue tetrazolium (NBT) staining. The causative gene for RBM is FHL1 encoding four and a half LIM domains.","Nervous system disease; Musculoskeletal disease"
"H02100","Peroxisomal fatty acyl-CoA reductase 1 disorder","Peroxisomal fatty acyl-CoA reductase 1 (FAR1) disorder is a peroxisomal disorder, that is also referred to as rhizomelic chondrodysplasia punctata type 4 (RCDP4). It is characterized by syndromic severe intellectual disability with cataracts, epilepsy, and growth retardation but without rhizomelia or skeletal abnormalities. Mutations in FAR1, producing fatty alcohols used in plasmalogen biosynthesis, were recently shown to cause this disease.","Congenital disorder of metabolism"
"H02332","Preaxial polydactyly","Polydactyly is the most common hereditary limb anomaly characterized by extra fingers. Preaxial polydactyly (PPD) refers to polydactyly where the additional digit grows toward the first digit of the hand or foot. Mutations in genes including GLI1, GL3 and SHH/ZRS, involved in Hedgehog pathway, result in preaxial polydactyly.","Congenital malformation"
"H00465","Fragile X syndrome","Fragile X syndrome (FXS) is a cognitive disorder caused by silencing of the fragile X mental retardation 1 gene (FMR1). Absence of the associated protein FMRP leads to the dysregulation of many genes creating a phenotype of ADHD, anxiety, epilepsy and autism.There are also several physical features commonly associated with FXS, including elongated faces, prominent ears, and macroorchidism. The most prevalent genetic aberration at the FMR1 locus arises from a noncoding CGG repeat in the 5'untranslated region.","Chromosomal abnormality"
"H00001","B-cell acute lymphoblastic leukemia","Acute lymphocytic leukemia (ALL) is a clonal stem cell malignancy of excessive lymphoblast proliferation. It is now understood that ALL and lymphoblastic lymphoma are the same disease entities at the morphologic and immunophenotypic levels and classified as either B- and T-cell lymphoblastic leukemia/lymphoma (B-ALL and T-ALL). In the case of B-ALL, numerous reports have demonstrated that recurring genetic abnormalities are associated with sufficiently unique clinical, immunophenotypic, and/or prognostic features so that they can be considered as distinct entities. The most common rearrangements observed in B-ALL are the t(12;21) (p13;q22) rearrangement resulting in expression of the ETV6-RUNX1 fusion (TEL-AML1); the t(1;19) (q23;p13) translocation that results in expression of the TCF3 (E2A) fusion partner, (also known as TCF3) TFPT-PBX1 fusion (E2A-PBX); the t(9;22) (q34;q11.2) 'Philadelphia' chromosome resulting in expression of the BCR-ABL1 fusion; and rearrangements of MLL (also known as KMT2A) at 11q23 to a diverse array of fusion partners. If none of these specific genetic abnormalities are found, the designation of 'B lymphoblastic leukemia/lymphoma, not otherwise specified,' is appropriate.","Cancer"
"H00233","MYH9-related disease","The autosomal dominant disorders, which are caused by mutation of gene encoding nonmuscle myosin heavy chain 9, May-Hegglin anomaly , Fechtner syndrome(FTNS), and Sebastian syndrome , share the triad of thrombocytopenia, large platelets and characteristic leukocyte inclusions (Dohle-like bodies). Epstein syndrome is clinically identical to FTNS, except Dohle-like bodies have not been described.","Cardiovascular disease"
"H02138","Hereditary hypophophatemic rickets with hypercalciuria","Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare autosomal recessive disorder that is characterized by reduced renal phosphate reabsorption, hypophosphatemia, and rickets. Patients present with hypercalciuria due to increased serum 1, 25-dihydroxyvitamin D levels and increased intestinal calcium absorption. HHRH is caused by mutations in the sodium-phosphate cotransporter gene SLC34A3.","Congenital disorder of metabolism"
"H00039","Basal cell carcinoma","Cancer of the skin is the most common cancer in Caucasians and basal cell carcinomas (BCC) account for 90% of all skin cancers. The vast majority of BCC cases are sporadic, though there is a rare familial syndrome basal cell nevus syndrome (BCNS, or Gorlin syndrome) that predisposes to development of BCC. In addition, there is strong epidemiological and genetic evidence that demonstrates UV exposure as a risk factor of prime importance. The development of basal cell carcinoma is associated with constitutive activation of sonic hedgehog signaling. The mutations in SMOH, PTCH1, and SHH in BCCs result in continuous activation of target genes. At a cellular level, sonic hedgehog signaling promotes cell proliferation. Mutations in TP53 are also found with high frequency (>50%) in sporadic BCC.","Cancer"
"H00805","Vitreoretinal degeneration","The inherited vitreoretinal degenerations are disorders of the eye characterized by early onset cataract, anomalies of the vitreous manifesting as optically empty vitreous, course fibrils, and membranes, and retinal detachment. These diseases include Stickler syndrome types I (STL1) and II (STL2), caused by mutations in COL2A1 and COL11A1 respectively. Snowflake vitreoretinal degeneration (SVD) is associated with a mutation in a KCNJ13, and Wagner syndrome (WGN1) with mutations in CSPG2. Knobloch syndrome (KNO) may also be caused by mutations in a collagen gene, COL18A1. In addition to Stickler syndrome and other chondrodysplasias, enhanced S-cone syndrome (ESCS) and autosomal dominant vitreoretinochoroidopathy (ADVIRC) are associated with vitreoretinal degeneration.","Nervous system disease"
"H01923","Microcephaly, short stature, and impaired glucose metabolism","Microcephaly, short stature, and impaired glucose metabolism (MSSGM) is a new syndrome of young onset diabetes, short stature and microcephaly with intellectual disability. The causal nonsense mutation in tRNA methyltransferase gene TRMT10A has been identified. TRMT10A is ubiquitously expressed but enriched in brain and pancreatic islets, consistent with the tissues affected in this syndrome. It has also been reported that mutation in the eukaryotic translation initiation factor 2 alpha (eIF2a) phosphatase gene, PPP1R15B, is associated with these symptoms.","Congenital malformation"
"H01749","Achondroplasia","Achondroplasia is the most common skeletal dysplasia and the most frequent cause of short-limbed dwarfism. It is usually recognised at birth because of its distinctive clinical and radiographic features. Newborn infants with achondroplasia typically present with disproportionate shortening of the limbs, a long and narrow trunk, a large head with frontal bossing and midface retrusion. This disease is caused by mutations of the transmembrane receptor FGFR3, an important regulator of bone growth. It is inherited in an autosomal dominant manner, but in the majority of cases it results from de novo mutations. The most common complications of achondroplasia are medullary and radicular compressions due to spinal stenosis and deformities of the lower limbs. Most individuals with achondroplasia have normal intelligence.","Congenital malformation"
"H00234","Pelger-Huet anomaly","Pelger-Huet anomaly is an autosomal dominant disorder characterized by abnormal nuclear shape and chromatin organization in blood granulocytes with skeletal abnormalities.","Hematologic disease"
"H00006","Hairy cell leukemia","Hairy cell Leukemia (HCL) is a chronic lymphoproliferative disorder that is defined, according to the WHO classification, as a mature (peripheral) B-cell neoplasm. HCL accounts for between 2-3% of all leukemia cases, with about 600 new cases diagnosed in the U.S. each year. With regard to genetic abnormalities of potential pathogenetic importance in HCL, only a few have been described. Mutations of p53 and Bcl-6 have been reported in about one-third of cases, but their functional significance is unclear. Over-expression of cyclin D1, an important cell cycle regulator, has been reported in cases of HCL as well as mantle cell lymphoma (MCL) and in a few cases of chronic lymphocytic leukemia among lymphoid malignancies.","Cancer"
"H02335","Preimplantation embryonic lethality","Preimplantation embryonic lethality (PREMBL), also known as early embryonic arrest, is one of the major causes of female infertility. Recently, a mutation in TLE6, which encodes a protein participating in the subcortical maternal complex (SCMC), was reported to cause this disease. The SCMC is composed of maternally expressed proteins and required for early embryonic cell division. Mutations in PADI6 has also been identified in individuals with PREMBL.","Reproductive system disease"
"H00462","Stuve-Wiedemann syndrome","Stuve-Wiedemann syndrome is an autosomal recessively inherited disorder characterized by congenital bone dysplasia like bowing of the long bones. Mutations in LIFR result in this disease.","Congenital malformation"
"H01782","Eosinophilic gastrointestinal disorder","Eosinophilic gastrointestinal disorder (EGID) is a disorder characterised by eosinophilic infiltration of the gastrointestinal tract. The most common form of EGID is Eosinophilic Esophagitis (EoE). Other forms of EGID include eosinophilic gastritis, eosinophilic enteritis, eosinophilic colitis and eosinophilic gastroenteritis (EGE). While these disorders are less frequent than EoE, their pathogenesis and treatment are probably similar. Clinically, patients with EGID often present with dysphagia, vomiting or abdominal pain. While the etiology remains unclear, there is a well documented association of atopy with EGID. Clinical studies in children and adults have demonstrated an association with food allergy.","Immune system disease; Digestive system disease"
"H00650","Allan-Herndon-Dudley syndrome","Allan-Herndon-Dudley syndrome (AHDS) is an X-linked mental retardation syndrome with neuromuscular involvement characterized by hypotonia, muscular hypoplasia and intellectual deficit. AHDS is caused by mutations in the SLC16A2 gene, encoding MCT8 which is a specific transporter for thyroid hormone T3.","Endocrine and metabolic disease"
"H02107","Bietti crystalline corneoretinal dystrophy","Bietti crystalline corneoretinal dystrophy (BCD) is an autosomal recessive retinal dystrophy characterized by crystalline deposits in the retina, followed by progressive atrophy of the retinal pigment epithelium (RPE), choriocapillaris, and photoreceptors. BCD usually occurs in the second or third decade of life. CYP4V2 has been identified as the causative gene for BCD.","Nervous system disease"
"H01544","Brazilian hemorrhagic fever","Brazilian hemorrhagic fever is an infectious disease caused by Sabia virus (SABV), a New World arenavirus in the Arenaviridae family of -ssRNA viruses, and transmitted by rodents. SABV was first isolated in 1993 in Brazil.","Infectious disease"
"H00496","Congenital hemidysplasia with ichthyosiform nevus and limb defects (CHILD)","Congenital hemidysplasia with ichthyosiform nevus and limb defects (CHILD) is an X-linked dominant, male-lethal trait with a lateralized inflammatory nevus and body hypoplasia. Loss of function of NSDHL, an enzyme involved in cholesterol biosynthesis leads to the condition.","Congenital malformation"
"H01776","Aicardi syndrome","Aicardi syndrome is a rare neurodevelopmental disorder. The main diagnostic features are agenesis of corpus callosum, chorioretinal lacunae, and infantile spasms. Along with agenesis of corpus callosum, typical brain abnormalities include polymicrogyria, periventricular and subcortical heterotopia, intracranial cysts, cerebellar abnormalities, and enlarged cisterna magna. Neurological abnormalities include microcephaly, optic nerve coloboma, developmental delay, mental retardation, intractable epilepsy, hypotonia and limb hypertonia with spasticity. The etiology of Aicardi syndrome is still unknown. However, as the disorder is only observed in females and in males with chromosome 47, XXY, it is assumed to be caused by a de novo mutation on the X chromosome and inherited in a dominant manner with lethality in males.","Congenital malformation"
"H01312","Enteroaggregative Escherichia coli (EAEC) infection","Enteroaggregative Escherichia coli (EAEC or EAggEC) infection is a cause of traveler's diarrhea and persistent watery diarrhea in young children and patients infected with HIV. EAEC adheres to the small intestine via aggregative adherence fimbriae. The adherent rods resemble stacked bricks and result in shortening of microvilli. Approximately 40% of EAEC strains produce a heat-stable toxin, EAST1.","Infectious disease"
"H01120","Proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome","Proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome (PVHH), also known as Fowler syndrome, is an autosomal-recessively inherited prenatal lethal disorder of brain angiogenesis, resulting in abnormally thickened and aberrant perforating vessels leading to hydranencephaly. Mutations and a large deletion in the FLVCR2 gene have been revealed in the families with Fowler syndrome. FLVCR2 encodes a transmembrane transporter of the major facilitator superfamily (MFS) hypothesized to be involved in regulation of growth, calcium exchange, and homeostasis.","Developmental disorder; Vascular disease"
"H00833","Neurodegeneration with brain iron accumulation","Neurodegeneration with brain iron accumulation (NBIA) is a group of progressive extrapyramidal and cognitive disorders characterized by iron accumulation predominantly in the globus pallidus, as well as extensive axonal spheroids in various regions of the brain. The most frequent genetic form is the pantothenate kinase-2 associated neurodegeneration (PKAN) with a mutation in the pantothenate kinase 2 (PANK2) gene. Other forms are associated with a mutation in phosphoslipase A2 (PLA2G6), and FTL (neuroferritinopathy). A significant proportion of children with an NBIA phenotype have no genetic diagnosis and there are additional as yet undiscovered genes that account for a number of these cases.","Nervous system disease"
"H00659","Shprintzen-Goldberg syndrome","Shprintzen-Goldberg syndrome (SGS) is a group of disorders characterized by craniosynostosis, neurologic abnormalities, and Marfanoid findings. It is a condition that involves skeletal changes and cardiovascular anomalies.","Congenital malformation"
"H01129","Brody myopathy","Brody myopathy is an autosomal recessive disorder of skeletal muscle function characterized by painless muscle contracture and exercise-induced impairment of muscle relaxation due to a defect of calcium reuptake. Mutations in the human ATP2A1 gene, that encodes one of the SERCA Ca(2+)-ATPases, cause Brody myopathy.","Nervous system disease; Musculoskeletal disease"
"H01915","Borjeson-Forssman-Lehmann syndrome","Borjeson-Forssman-Lehmann syndrome (BFLS) is a rare, X-linked mental retardation syndrome. BFLS is characterized by severe intellectual disability, epilepsy, microcephaly, coarse facial features, long ears, short stature, obesity, gynecomastia, tapering fingers, and shortened toes. Mutations in the zinc finger gene PHF6 are the cause of BFLS.","Congenital malformation"
"H00454","Oral-facial-digital syndrome","Oral-facial-digital syndrome is a group of heterogeneous disorders characterized by malformations of the face, oral cavity and digits. OFD type I is a male lethal disorder and due to mutations in the OFD1 gene on the X chromosome. OFD type IV is due to mutations in the TCTN3 gene and patients have tibial dysplasia. OFD type V is due to mutations in the DDX59 gene and patients show the core features of cleft palate, lobulated tongue, and polydactyly.","Congenital malformation"
"H01586","Acquired pure red cell aplasia","Pure red cell aplasia (PRCA) is a rare condition characterised by selective inhibition and the absence of red cell precursors in the bone marrow with consequent anaemia and reticulocytopenia in the presence of normal granulocytic and megakaryocytic lineages. RPCA can be classified into congenital and acquired. Congenital PRCA is also known as Diamond-Blackfan anemia [DS:H00237] and is a disease of infancy and early childhood. The aetiology of acquired PRCA can be subclassified into primary and secondary. Primary PRCA is defined when no aetiology can be identified using available investigations. The causes of secondary PRCA are again diverse and can be due to infections (viral, bacterial, etc.), drugs (erythropoietin, carbamazepine, etc.), collagen vascular disorders (rheumatoid arthritis, systemic lupus erythematosus, etc.), malignancies (e.g. thymoma), ABO-incompatible haematopoietic stem cell transplantation, and pregnancy. Depending on the cause, the course can be acute and self-limiting or chronic with rare spontaneous remissions. PRCA can be easily diagnosed when isolated anaemia, in the presence of normal white cell and platelet counts, is associated with a marrow of normal cellularity in which there is an almost complete absence of erythroblasts but normal myeloid cells and megakaryocytes. Primary, or secondary PRCA not responding to treatment of the underlying diseases, is treated as an immunologically-mediated disease. The therapeutic plan usually focuses on the sequential use of various immunosuppressive therapies until a remission is obtained.","Hematologic disease; Immune system disease"
"H02303","Alopecia-mental retardation syndrome","Alopecia-mental retardation syndrome (APMR) is a rare autosomal recessive disorder characterized by total or partial absence of hair from the scalp and other parts of the body and associated with mental retardation. Three regions associated with APMR have been identified. Recently, a novel pathogenic, missense mutation in the AHSG has been revealed. AHSG maps within APMR linkage region 1 (APMR1) as reported before.","Congenital malformation"
"H02131","UV-sensitive syndrome","UV-sensitive syndrome (UV(S)S) is an autosomal recessive disorder characterized by mild photosensitivity in sun-exposed areas of the skin, with freckling and telangiectasia, but without the high propensity to skin cancer. UV(S)S and Cockayne syndrome [DS:H00076] are deficient in transcription-coupled nucleotide excision repair (TC-NER), a subpathway of nucleotide-excision repair (NER) that rapidly removes transcription-blocking DNA damage. The cellular and biochemical responses of UV(S)S and Cockayne syndrome cells to UV light are indistinguishable. Some UV(S)S cases carry mutations in the Cockayne syndrome genes ERCC8 or ERCC6 (also known as CSA and CSB, respectively).","Skin disease"
"H00666","Peutz-Jeghers syndrome","Peutz-Jeghers syndrome (PJS) is an autosomal dominant condition in which multiple characteristic polyps occur throughout the gastrointestinal tract. Mucocutaneous pigmented lesions, especially of the vermilion border of the lips, are seen in almost all patients. PJS patients have a considerably increased risk of developing intestinal malignancies. The only known cause for PJS is STK11 mutation.","Gastrointestinal disease"
"H00202","Hepatic porphyria","Hepatic porphyrias are diseases due to marked deficiencies of enzymes in the heme biosynthetic pathway. Clinical manifestations in porphyria are neurovisceral or cutaneous as well as hematic or hepatic.","Congenital disorder of metabolism"
"H00030","Cervical cancer","Cervical cancer is the second largest cause of cancer-related death in women worldwide, and it occurs following persistent infection, sometimes for decades, with a specific subset of human papillomavirus (HPV) types, particularly types 16, 18, 33 and 42. Experimental studies show that the E6 and E7 genes of these high risk HPVs are oncogenes that deregulate key cell cycle controls. The E6 and E7 oncoproteins bind respectively to the p53 and Retinoblastoma (Rb) tumor suppressor proteins, which are involved in the regulation of growth control. The abnormalities in other cellular genes found in cervical cancer, including mutations in ras family of genes, and amplification in EGFR and ERBB2, may also play an important role in carcinogenesis and the aggressiveness of cervical tumors, although to date the role of most of these genetic abnormalities does not appear to be as important as the role of HPV.","Cancer"
"H01324","Lymphocytic choriomeningitis","Lymphocytic choriomeningitis (LCM) is an infectious disease caused by Lymphocytic choriomeningitis virus (LCMV), an arenavirus in the Arenaviridae family of -ssRNA viruses, and transmitted by rodents. LCMV was the first isolated in 1933 in St. Louis, USA.","Infectious disease"
"H01116","Choroideremia","Choroideremia (CHM) is an X-linked retinal dystrophy characterized by progressive degeneration of the choriocapillaris, retinal pigment epithelium and photoreceptors. CHM is caused by mutations in the CHM gene, which encodes a protein involved in vesicular trafficking.","Nervous system disease"
"H01572","Cole-Carpenter syndrome","Cole-Carpenter syndrome (CCS) is a severe bone fragility disorder that is characterized by frequent fractures, craniosynostosis, ocular proptosis, hydrocephalus, and distinctive facial features. CCS was first described in 1987 as a newly recognized type of osteogenesis imperfecta (OI). Despite its apparent extreme rarity, CCS is commonly classified as a separate OI-like disorder. CCS is caused by a specific de novo mutation in P4HB, the gene that encodes protein disulfide isomerase (PDI), that impairs the disulfide isomerase activity. Mutations in SEC24D, a gene encoding a component of the COPII complex machinery, have been reported to cause CCS as well.","Congenital malformation"
"H00692","Lowe syndrome","Lowe Syndrome, or Oculocerebrorenal Dystrophy (OCRL) is a multisystem disorder characterised by anomalies affecting the eye, the nervous system and the kidney. This is a rare X-linked disorder caused by mutations in the OCRL1 gene which encodes the phosphatidylinositol enzyme (4, 5) biphosphate 5-phosphatase present in the Golgi complex. The symptoms of Lowe syndrome include congenital cataracts and glaucoma, delay in neuropsychomotor development, cognitive deficits, and renal tubular abnormalities.","Inherited metabolic disease; Nervous system disease"
"H01740","Macrothrombocytopenia","Macrothrombocytopenia (MTP) is a heterogeneous group of disorders characterized by enlarged and reduced numbers of circulating platelets, sometimes resulting in abnormal bleeding. The clinical presentations of MTP-affected individuals vary considerably and range from no symptoms to a severe bleeding tendency. MTP-causing mutations have been reported in several genes, involved in various functions such as cell signaling, cytoskeleton organization, and gene expression. Among these, the most common is MYH9, which is responsible for MYH9-related disease. The second most common are GP1BA, GP1BB, and GP, which are responsible for Bernard-Soulier syndrome.","Hematologic disease"
"H01912","Congenital lipomatous overgrowth, vascular malformations, and epidermal nevi","Congenital lipomatous overgrowth, vascular malformations, and epidermal nevi (CLOVE) syndrome is a recently delineated disorder that comprises vascular malformations (typically truncal), dysregulated adipose tissue, scoliosis, enlarged bony structures (typically of the legs) without progressive or distorting bony overgrowth. The key feature of this syndrome is a truncal lipomatous mass of variable size that is noted at birth. The fatty growths often extend from the trunk into the retroperitoneum, mediastinum, thoracic cavity, and epidural space. Deeper fast-flow and slow-flow vascular anomalies become evident early in childhood. Most acral deformities become accentuated with growth, are often symmetrical, are not rapidly progressive, and are commonly misdiagnosed as Proteus syndrome. This syndrome is caused by somatic activating mutations in PIK3CA.","Congenital malformation"
"H00498","Gnathodiaphyseal dysplasia","Gnathodiaphyseal dysplasia is a rare skeletal syndrome with autosomal dominant inheritance. It is characterized by cemento-osseous lesions of the jawbone, bone fragility, and sclerosis of tubular bones. Missense mutations of GDD1, which shows homology to TMEM16E, were identified.","Musculoskeletal disease"
"H01778","Ullrich disease","Ullrich disease or Ullrich congenital muscular dystrophy (UCMD) is a severe congenital disorder characterized clinically by generalized muscle weakness, contractures of the proximal joints and hyperextensibility of the distal joints and begins from birth or early infancy. Mutations in the three collagen VI genes COL6A1, COL6A2 and COL6A3 cause Ullrich disease.","Nervous system disease; Musculoskeletal disease"
"H02109","Combined malonic and methylmalonic aciduria","Combined malonic and methylmalonic aciduria (CMAMMA) is a rare recessive inborn error of metabolism characterised by elevations of urine malonic acid and methylmalonic acid. Unlike classic phenotype of methylmalonic acidemia, malonyl-CoA decarboxylase activity is normal. Mutations in ACSF3 have been identified as a cause of CMAMMA. ACSF3 encodes an enzyme that catalyzes the initial reaction in intramitochondrial fatty acid synthesis.","Congenital disorder of metabolism"
"H00008","Burkitt lymphoma","Burkitt lymphoma (BL) is a highly aggressive mature B-cell non-Hodgkin's lymphoma consisting of endemic, sporadic, and immunodeficiency-associated variants. Endemic BL (eBL) affects children and young adults in Africa and some other geographical areas and carries Epstein-Barr virus (EBV) in more than 95% of cases. In contrast, sporadic BL (sBL) among adolescents in Europe and North America are mostly EBV-negative. A third type of BL is associated with HIV-infection in adults. All of these subtypes possess chromosomal rearrangements of the c-myc oncogene, the genetic hallmark of BL that contributes to lymphomagenesis through alterations in cell cycle regulation, cellular differentiation, apoptosis, cellular adhesion, and metabolism. Many BL carry point mutation in the p53 tumor suppressor gene or other defects in the p14ARF-MDM2-p53 pathway, and inactivation of the p16INK4a gene by promoter methylation or homozygous deletion. This indicates that disruption of both the pRb and p53 tumor suppressor pathways is critical for BL development.","Cancer"
"H00834","Guanidinoacetate methyltransferase deficiency","Guanidinoacetate methyltransferase (GAMT) deficiency is an autosomal recessive inborn error of creatine biosynthesis caused by a deficiency of hepatic guanidinoacetate methyltransferase, resulting in a lack of creatine and an accumulation of guanidinoacetic acid, the precursor of creatine. GAMT deficiency is characterized by developmental arrest or delay in the first few months of life with epilepsy and extrapyramidal movements as common features. Neurologic signs and symptoms are variable, and autistic spectrum disorders are sometimes seen in older affected individuals. Pathophysiology of GAMT deficiency is thought that the accumulation of guanidinoacetate can interact with neuronal GABAA receptors and cause the neurological dysfunction which underlies these symptoms.","Inherited metabolic disease"
"H00695","Mal de Meleda","Mal de Meleda is an autosomal recessive palmoplantar keratoderma characterized by erythema of the palms and soles, followed by a diffuse yellowish hyperkeratosis. Keratinization extends onto the dorsal surface of the hands and feet as the patient ages. It is associated with brachydactyly and nail abnormalities. Mental retardation may also occur.","Congenital malformation"
"H01747","Costello syndrome","Costello syndrome (CS) is a rare multiple congenital abnormality syndrome. Patients present with the typical coarse face, deep palmar and plantar creases, redundant and loose skin, severe failure to thrive, congenital heart defect, and mild to severe mental retardation. Hyperpigmentation and papillomas can also be present. They have an increased risk of malignancy. The majority of patients show a mutation in HRAS.","Congenital malformation"
"H01575","Roifman syndrome","Roifman syndrome is a multi-system disorder with a physical phenotype that includes B-cell immunodeficiency, intra-uterine and postnatal growth retardation, spondyloepiphyseal dysplasia, retinal dystrophy, and characteristic facial dysmorphism. Recently, whole-genome sequencing of Roifman syndrome patients have demonstrated that Roifman syndrome is caused by compound heterozygous single-nucleotide variants (SNVs) in the minor spliceosomal small nuclear RNA (snRNA) gene RNU4ATAC, which was already implicated in a severe congenital disorder, microcephalic osteodysplastic primordial dwarfism, type I (MOPD1) [DS:H00993]. Roifman syndrome is phenotypically distinct from MOPD1.","Congenital malformation"
"H01111","Cortisone reductase deficiency","Cortisone reductase deficiency (CORTRD) is a rare abnormality of cortisone metabolism. There are close phenotypic similarities between CRD and polycystic ovary syndrome (PCOS). PCOS is a common endocrine disorder characterized by hirsutism, menstrual irregularity, anovulatory infertility, obesity, insulin resistance and hyperandrogenism. 11beta-HSD1 is a dimeric enzyme that catalyzes the reduction of cortisone to cortisol within the endoplasmic reticulum. And loss of its activity results in CRD. Mutations in H6PD, which encodes an enzyme supplying cofactor for the reaction, also have been identified as the cause of CRD.","Endocrine and metabolic disease"
"H01323","Enteritis due to Norovirus","Enteritis due to Norovirus is a major nonbacterial gastroenteritis worldwide. Norovirus is one of five genera of the family Caliciviridae of +ssRNA viruses. Human norovirus, previously known as Norwalk virus, was first identified during an outbreak of gastroenteritis in Norwalk, Ohio, USA.  Noroviruses are currently categorized into at least seven genogroups (GI-GVII) that are further divided into more than 40 genotypes. Genogroup GI, GII, and GIV viruses infect humans. Human Noroviruses are primarily transmitted by the fecal-oral route, either by person-to-person contact, or by ingestion of contaminated food or water. Moreover, they significantly contribute to foodborne diseases.","Infectious disease"
"H00037","Rhabdomyosarcoma","Rhabdomyosarcomas (RMSs) are soft tissue sarcomas that are one of the most common neoplasms in children and adolescents. RMSs are presumed to be associated with the skeletal muscle lineage, although those tumors can be present in organs histologically lacking skeletal muscle, like prostate, urinary bladder or gallbladder. RMS comprises a heterogeneous into two major histologic subtypes, embryonal (ERMS) and alveolar (ARMS). Alveolar rhabdomyosarcoma (ARMS) is a pediatric sarcoma that typically occurs in older children predominantly arising in the trunk and extremities, and exhibits a worse prognosis than other types of RMSs. ARMS is associated with 2;13 or 1;13 chromosomal translocations, which generate PAX3-FOXO1A and PAX7-FOXO1A fusion products, respectively. These translocations result in altered expression, function, and subcellular localization of the fusion products relative to the wild-type proteins, and ultimately contribute to oncogenic behavior by modifying growth, differentiation, and apoptosis pathways.","Cancer"
"H00205","Peroxisome biogenesis disorder","Peroxisome biogenesis disorder (PBD) is a group of lethal disorders caused by mutation of peroxisomal biogenesis factor (PEX) genes. PBDs fall into 4 main phenotypic classes; Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD), Infantile Refsum disease (IRD), and rhizomelic chondrodysplasia punctata (RCDP1). Zellweger syndrome is the most severe form and results in neurological dysfunction, craniofacial abnormalities, eye abnormalities, hepatomegaly, and chondrodysplasia punctata. The patients of NALD and IRD have similar symptoms, but they survive considerably longer than ZS. NALD is the intermediate form and IRD is the mildest form.","Inherited metabolic disease; Nervous system disease; Liver disease; Peroxisomal disease"
"H02136","Branched-chain ketoacid dehydrogenase kinase deficiency","Branched-chain ketoacid dehydrogenase kinase (BCKDK) deficiency is a familial comorbid intellectual disability, autism, and epilepsy, caused by mutations in the BCKDK. Patients also showed abnormally low plasma levels of branched-chain amino acids.","Congenital disorder of metabolism"
"H00661","MASS phenotype","MASS Phenotype (Mitral valve prolapse, Aortic dilatation without dissection, Skeletal and Skin abnormalities) is one of the FBN1-related disorders similar to Marfan syndrome. Reduced expression of FBN1 due to a 4 bp deletion in exon 41 is the cause of MASS phenotype.","Congenital malformation"
"H00453","Branchio-oto-renal syndrome","Branchio-oto-renal (BOR) syndrome and Branchiootic (BO) syndrome show overlapping phenotypes of bilateral conductive hearing loss, branchial defects, and facial abnormalities. Indivisuals with BOR syndrome have renal anomalies as well. Mutations in the EYA1 or its transcription cofactor SIX1 and SIX5 are responsible for the diseases.","Congenital malformation"
"H01581","IgA nephropathy","Primary IgA nephropathy is an immune-complex-mediated glomerulonephritis defined immunohistologically by the presence of glomerular IgA deposits accompanied by a variety of histopathologic lesions. It is known to be the most prevalent primary chronic glomerular disease worldwide. Because of the critical interaction between an intrinsic antigen (galactose-deficient IgA1) and circulating anti-glycan antibodies, IgA nephropathy can be considered an autoimmune disease. Since the features of IgA nephropathy identified by light microscopy are nonspecific, immunofluorescence or immunoperoxidase studies demonstrating a predominant deposition of IgA are essential to establish a definitive diagnosis of IgA nephropathy. Genetic factors undoubtedly influence the pathogenesis of IgA nephropathy. Genomewide association studies have identified common susceptibility loci in the absence of a priori mechanistic hypotheses.","Immune system disease; Urinary system disease"
"H02304","Combined D-2- and L-2-hydroxyglutaric aciduria","Combined D-2- and L-2-hydroxyglutaric aciduria (D,L-2-HGA), characterized by elevated levels of both D-2-hydroxyglutarate (HG) and L-2-HG in body fluids, mainly manifests in a severe neonatal epileptic encephalopathy, absence of developmental progress, and often early death. Recessive mutations in SLC25A1, the mitochondrial citrate carrier, have been reported in individuals with D,L-2-HGA.","Congenital disorder of metabolism"
"H01521","Pneumocystis pneumonia","Pneumocystis pneumonia (PCP) is an infectious disease caused by Pneumocystis jirovecii that belongs to the genus Pneumocystis. Members of the genus Pneumocystis are unicellular, eukaryotic organisms that reside in the lungs of many mammals. The 5 main species are have been identified. PCP is a potentially life-threatening disease that occurs in immunocompromised patients.","Infectious disease"
"H01713","Diffuse panbronchiolitis","Diffuse panbronchiolitis (DPB) is a chronic inflammatory lung disease, which predominantly affects East Asians. Clinically, DPB is characterized by chronic inflammation of the respiratory bronchioles and sinobronchial infection. While DPB is frequently compared with cystic fibrosis, a common genetic disease encountered in Caucasians, neither pancreatic insufficiency nor any obvious abnormalities of the sweat electrolytes are seen in DPB, and the two are considered to be entirely different diseases. Immunogenetic studies revealed a strong association with human HLA-B54 in Japanese, whereas an association with HLA-A11 was reported in Koreans. These findings imply that a major susceptibility gene may be located between the HLA-A and HLA-B loci on the short arm of human chromosome 6. Recently, novel mucin-like genes has been cloned in this candidate region. And it was found that their polymorphisms were associated with DPB. Over the past two decades, DPB has shifted from being a near-fatal to a treatable disease. A significant improvement in the prognosis of this disease has been attributed to the long-term use of macrolides. The five-year survival rate increased to about 90% after treatment with erythromycin became widely used.","Respiratory disease"
"H02196","X-linked creatine deficiency syndrome","Creatine deficiency syndromes are inborn errors of metabolism resulting in a progressive encephalopathy with early onset mental retardation, extrapyramidal features, and drug resistant epilepsy. X-linked creatine deficiency syndrome is caused by mutations in SLC6A8 gene that encodes creatine transporter.","Congenital disorder of metabolism"
"H01377","Mitchell-Riley syndrome","Mitchell-Riley syndrome is a neonatal diabetes syndrome that involves abnormalities of the anterior gut as well as diabetes. Patients with this syndrome are typically diagnosed within the first week of life and generally die within their first year of life. Mutations in rfx6 have been associated with Mitchell-Riley syndrome.","Inherited metabolic disease"
"H01979","Overhydrated hereditary stomatocytosis","Overhydrated hereditary stomatocytosis (OHST), which is clinically characterized by a hemolytic anemia, is a rare, dominantly inherited disorder of red blood cells (RBCs) associated with increased membrane permeability to monovalent cations and increased activity of the Na+K+-ATPase. The influx of Na+ exceeds the loss of K+ causing water influx and resulting in swollen erythrocytes, hemolysis, and stomatocyte formation. The OHST phenotype is also associated with a dramatic decrease or the absence of the 32-kDa membrane raft protein stomatin. OHST diagnosis is based on a hemolytic anemia associated with a massive right shift of the osmotic gradient ektacytometry curve and a decreased osmotic resistance, together with a major increase in a monovalent cation leak. Recently, OHST was found to be linked to amino acid substitutions in Rh-associated glycoprotein (RhAG).","Hematologic disease"
"H01145","Atransferrinemia","Atransferrinemia is a rare autosomal recessive disorder characterized by iron overload and hypochromic anemia. A few case of human atransferrinemia with mutations in the transferrin gene has been reported.","Inherited metabolic disease; Hematologic disease"
"H00097","Chemokine receptor defect","WHIM (an acronym for warts, hypogammaglobulinemia, infections and myelokathexis, a form of neutropenia) syndrome is a congenital immunodeficiency disease characterized by neutropenia, hypogammaglobulinemia and susceptibility to human papillomavirus (HPV) infection. Affected individuals have mutations that variably truncate the cytoplasmic tail domain of CXC chemokine receptor 4 (CXCR4). Leukocytes expressing truncated CXCR4 display enhanced responses to the receptor ligand CXCL12, including chemotaxis, which likely impair their trafficking and contribute to the immunohematologic clinical manifestations of the syndrome.","Primary immunodeficiency"
"H01383","Hyperlipoproteinemia type IIa","Familial hypercholesterolemia is characterized by severely elevated low-density lipoprotein (LDL) cholesterol, xanthomas, and the development of premature cardiovascular disease. Hyperlipoproteinemia type IIa is an autosomal dominant disorder caused by mutations in the LDL receptor. The LDL receptor gene consists of a number of distinct functional domains such as signal sequence, ligand binding, and so on. There are more than 1600 mutations in the LDLR gene that can cause familial hypercholesterolemia, accounting for up to 95% of all cases.","Congenital disorder of metabolism"
"H00251","Thyroid dyshormonogenesis","Thyroid dyshormonogenesis is a genetically heterogeneous group of inherited disorders in the enzymatic cascade of thyroid hormone synthesis that result in congenital hypothyroidism due to genetic defects in the synthesis of thyroid hormones.","Endocrine disease"
"H00063","Spinocerebellar ataxia (SCA)","The autosomal dominant spinocerebellar ataxias (SCAs) are a group of progressive neurodegenerative diseases characterised by loss of balance and motor coordination due to the primary dysfunction of the cerebellum. Compelling evidence points to major aetiological roles for transcriptional dysregulation, protein aggregation and clearance, autophagy, the ubiquitin-proteasome system, alterations of calcium homeostasis, mitochondria defects, toxic RNA gain-of-function mechanisms and eventual cell death with apoptotic features of neurons during SCA disease progression.","Neurodegenerative disease"
"H02350","Dyschromatosis universalis hereditaria","Dyschromatosis universalis hereditaria (DUH) is a group of congenital pigmentary disorders characterized by asymptomatic hypo- and hyper-pigmented macules of irregular size and shape which appear early in life. At least two causative genes, ABCB6 and SASH1, have been reported.","Skin disease"
"H00407","Peroxisomal beta-oxidation enzyme deficiency","Peroxisomal beta-oxidation enzyme deficiency is a group of inherited peroxisomal diseases caused by mutation of one of genes that encode peroxisomal fatty acid beta-oxidation system enzymes. The system includes straight-chain acyl-CoA oxidase (ACOX1), 2-methylacyl CoA racemase (AMACR), D-bifunctional protein (DBP) and sterol carrier protein X (SCPx). It is known that some types of fatty acids including very-long-chain fatty acids (VLCFA), branched-chain fatty acid, and the bile acid synthesis intermediates, rely fully on peroxisomes for beta-oxidation. The enzyme defects result in the accumulation of these fatty acids in many organs. The clinical manifestations mimic those of the Zellweger syndrome spectrum. [DS:H00205]","Congenital disorder of metabolism"
"H00635","Aniridia","Aniridia is a congenital, bilateral ocular malformation defined as iris aplasia or hypoplasia. It can be either isolated or accompanied by other ocular defects. Aniridia is caused by decreased dosage of the PAX6, a master regulatory gene that induces eye formation in a broad range of animals. Recently, it has been reported that aniridia is also caused by heterozygous mutations in the ELP4 gene and TRIM44 gene.","Congenital malformation"
"H02162","Viral hepatitis","Viral hepatitis is liver inflammation due to infection by viruses. There are five major hepatotropic viruses, which are different in viral taxonomy. Among them hepatitis B virus (HBV) and hepatitis C virus (HCV) are oncoviruses associated with hepatocellular carcinoma [DS:H00048].","Infectious disease"
"H01946","Glycogen storage disease type XI","Glycogen storage disease type XI (GSD-XI) is an autosomal recessive disorder of glycogen metabolism. GSD-XI is caused by mutations in the LDHA gene, which encodes lactate dehydrogenase.","Inherited metabolic disease"
"H00894","FG syndrome","FG syndrome (FGS), also known as Opitz-Kaveggia syndrome, is a rare X-linked multiple congenital anomaly/mental retardation (MCA/MR) disorder characterized by high clinical variability and genetic heterogeneity. The cardinal features of the syndrome are congenital hypotonia, delayed development of speech, relative macrocephaly (as compared to height and weight), anal anomalies or severe constipation, and dysmorphic facial features. Five loci have so far been linked to this phenotype on the X chromosome. A recurrent missense mutation in the MED12 gene has been identified as the cause for the subset of FGS cases. Filamin A gene (FLNA) and CASK gene mutations could be another causes of FG syndrome.","Congenital malformation"
"H01348","Mitochondrial phosphate carrier deficiency","Mitochondrial phosphate carrier deficiency (MPCD) is a novel disorder of oxidative phosphorylation caused by mutation in the SLC25A3 gene. The mitochondrial phosphate carrier SLC25A3 transports inorganic phosphate into the mitochondrial matrix, which is essential for the aerobic synthesis of adenosine triphosphate (ATP). The patients present with severe neonatal lactic acidosis, hypertrophic cardiomyopathy and generalised muscular hypotonia.","Congenital disorder of metabolism"
"H00438","Nasu-Hakola disease","Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), or Nasu-hakola disease is an autosomal recessive inherited disorder. It is characterized by repeated fractures occurring during adolescence and progressive presenile dementia in the fourth decade. The disease is caused by a mutation in the TREM2 or DAP12 gene that regulates osteoclast differentiation. TREM2-DAP12 is also expressed by microglia, thus neurological impairments seen in this disease are considered to be directly caused by microglial dysfunstion.","Congenital disorder of metabolism"
"H00860","Benign hereditary chorea","Benign hereditary chorea (BHC) is a rare, autosomal dominant, static disorder characterized by onset of chorea in conjunction with hypothyroidism and respiratory problems. Features supporting this diagnosis include normal general examination with no dysmorphic features, broadly normal intellectual development with no regression or loss of cognitive skills, absence of other significant neurologic disturbances, and, with the exception of chorea, normal neurologic examination findings. Mutations in the TTF1 gene encoding the thyroid transcription factor-1 have been identified in a number of BHC patients, suggesting that aberration of TTF1 transcriptional function or haploinsufficiency is associated with this disorder. TTF1, belonging to the NKX2 homeodomain transcription factor family, has been implicated in several important molecular pathways essential for brain, thyroid and lung morphogenesis.","Nervous system disease"
"H00632","Heterotaxy","Heterotaxy, or situs ambiguus, is an abnormal arrangement of the thoracic and abdominal viscera. The phenotype with mirror-image reversed left-right axis is called situs inversus, while partial alterations in the left-right organization is referred to as heterotaxy. Heterotaxy is associated with perturbation of nodal signaling during embryogenesis.","Congenital malformation"
"H02165","Colorado tick fever","Colorado tick fever is an infectious disease caused by Colorado tick fever virus (CTFV), a cortivirus in the Reoviridae family of dsRNA viruses, and transmitted by Rocky Mountain wood tick (Dermacentor andersoni). CTFV was first isolated in 1944 in the Rocky Mountain region.","Infectious disease"
"H02357","Congenital hypomyelinating neuropathy","Congenital hypomyelinating neuropathy (CHN) is a rare congenital neuropathy, often accompanied by arthrogryposis, that is characterized by prenatal onset, areflexia, hypotonia, hypomyelination, and slowed nerve conduction velocities. Previous reports of genetic analyses of patients have described mutations in genes known to be important in myelination.","Nervous system disease"
"H00400","Parainfluenza infection","Human parainfluenza viruses (HPIV) are single-stranded RNA viruses belonging to the paramyxovirus family. They are the second most common causes of pediatric lower respiratory tract diseaseleading to hospitalization after respiratory syncytial virus. It can cause repeated infections throughout life, causing flu-like illness.","Infectious disease"
"H00858","Marie-Unna hereditary hypotrichosis","Marie Unna hereditary hypotrichosis (MUHH) is an autosomal dominant form of hereditary hair loss. It is characterized by sparse or absent scalp hair, eyebrows, and eyelashes at birth. Coarse and wiry hair is progressively lost in this disease. Responsive mutations are found in U2HR, an inhibitory upstream open reading frame in the 5'-untranslated region of the HR gene. Recently, a missense mutation of EPS8L3 in MUHH has been identified.","Congenital malformation"
"H00064","Ataxia telangiectasia","Ataxia-telangiectasia (AT) is an autosomal recessive disorder with a birth frequency of about 1 in 300 000. It is a progressive neurodegenerative disease associated with abnormal eye movements and cutaneous telangiectasia, immunodeficiency, and premature aging. The product of the causative gene ATM is a 350 kDa protein of the phosphatidylinositol 3-kinase family that is involved in mitogenic signal transduction, intracellular protein transport, and cell cycle control.","Neurodegenerative disease; Primary immunodeficiency"
"H01384","Mitochondrial recessive ataxia syndrome","Mitochondrial recessive ataxia syndrome (MIRAS) is the mitochondrial disease, that is caused by mutations of the POLG1 gene encoding the mitochondrial DNA polymerase gamma enzyme. MIRAS includes the sensory ataxia neuropathy dysarthria and ophthalmoplegia (SANDO) and Spinocerebellar ataxia with epilepsy (SCAE). MIRAS is a common cause of autosomal recessive juvenile- or adult-onset ataxia, at least in Scandinavia. Most cases of SANDO present with an initial stage of sensory neuropathy, a second stage of progressive external ophahlmoplegia and dysarthria, which is then followed by other symptoms, often with epilepsia or myoclonus.","Inherited metabolic disease; Mitochondrial disease"
"H00256","Familial glucocorticoid deficiency","Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disease characterized by glucocorticoid deficiency despite high levels of plasma ACTH. Affected individuals typically present within the first few months of life with symptoms related to cortisol deficiency, including recurrent illnesses or infections, hypoglycemia, convulsions, failure to thrive and shock. The disease is life threatening if untreated. Glucocorticoid replacement is the recommended treatment. It has been reported that FGD is caused by mutation of the ACTH receptor (MC2R) and the accessory protein (MRAP).","Endocrine disease"
"H02501","Occipital cortical malformation","Occipital cortical malformation (OCCM) is an autosomal recessive disorder caused by mutations in LAMC3. OCCM is characterized by thickening and smoothening of the occipital cortex along with polymicrogyria. LAMC3 gene encodes the gamma 3 chain of the laminin family proteins, which play a crucial part in cell differentiation, migration, and adhesion.","Congenital malformation"
"H01142","Ehrlichia ewingii infection","Human ehrlichiosis is a recently recognized tick-borne infection. Ehrlichia ewingii has been identified as a cause of human disease in addition to formerly known pathogenic Ehrlichia species.","Infectious disease"
"H00090","NK cell defects","A patient with a mutation in CD16, also known as FcgRIIIa, has been identified. He was a 3-year-old boy, and suffered from recurrent viral respiratory tract infections since birth. CD16 is part of the FcgRIII found on NK cells as well as macrophages and some T cells. The receptor allows NK cells to phagocytose organisms or cells coated with IgG in the absence of MHC (antibody-dependent cellular cytotoxicity). The mutation disrupts NK cell function and is associated with NK cytopenia. The patient also had severe clinical problems after BCG vaccination.","Primary immunodeficiency"
"H01370","SHORT syndrome","SHORT syndrome is a rare autosomal-dominant disorder characterized by short stature, hyperextensibility of joints, hernias, ocular depression, ophthalmic anomalies, teething delay, partial lipodystrophy, insulin resistance, and facial dysmorphic signs. Mutations in PIK3R1 cause this syndrome.","Congenital malformation"
"H01714","Chronic obstructive pulmonary disease (COPD)","Chronic obstructive pulmonary disease (COPD) is a representative chronic inflammatory disorder of the lungs that includes chronic bronchitis and emphysema. COPD is characterized by airway inflammation and progressive airflow obstruction, most commonly caused by cigarette smoking. The major symptoms of which patients complain are cough, breathlessness, and sputum production. COPD is associated with underlying inflammation in response to chronic exposure to noxious particulates and gases and with a number of comorbid conditions. The onset of COPD generally occurs in the 6th to 8th decades of life. Early onset COPD is defined as disease onset before the age of 50 years, irrespective of smoking history. The presence of persons with early onset, severely reduced pulmonary function suggests that individuals may vary in their genetic susceptibility to the effects of smoking. Alpha-1-antitrypsin deficiency is the only proven genetic risk factor for COPD. Bronchodilators are the mainstay of treatment since they improve lung function and reduce acute exacerbations. Long-acting inhaled bronchodilators are recommended as first line treatment for patients with persistent symptoms.","Lung disease"
"H02191","Noonan-like syndrome with loose anagen hair","Noonan-like syndrome with loose anagen hair (NSLH) is characterized by features similar to those observed in Noonan syndrome. Besides, the most characteristic feature is the hair anomaly, including easily pluckable, sparse, thin, slow growing. NSLH is caused by the mutations in SHOC2. Recently, the novel NSLH with mutations in PPP1CB has been identified.","Congenital malformation"
"H01526","Legg-Calve-Perthes Disease","Legg-Calve-Perthes disease (LCPD) is a particular type of femoral head necrosis occurring in children. It is more common among boys, and bilateral involvement occurs in 8-24% of cases. The disease is usually diagnosed among children under age 14 years, with a peak onset between 5 and 8 years of age. There is delayed skeletal maturation and impaired growth. In addition to congenital abnormalities, LCPD is associated with greater risk of cardiovascular diseases and diseases of the blood. Most cases are sporadic, but familial cases have been described. It has been reported that COL2A1 mutations are associated with this disease.","Musculoskeletal disease"
"H00269","Primary microcephaly","Autosomal recessive primary microcephaly (MCPH) is a neurodevelopmental disorder characterized by reduced skull circumference and brain volume.","Congenital malformation"
"H00867","Radioulnar synostosis with amegakaryocytic thrombocytopenia","This disease is a rare combination of proximal radio-ulnar synostosis and congenital amegakaryocytic thrombocytopenia. Bruising and bleeding problems are observed since birth in affected individuals. The disease is related with HOXA11 mutation.","Congenital malformation"
"H01189","Transaldolase deficiency","Transaldolase (TALDO) deficiency is an inborn error of the pentose phosphate pathway (PPP), presenting primarily with liver disease and variable clinical course. TALDO is one of the key enzymes the PPP. The severity of the symptoms can vary, ranging from fetal hydrops to slowly progressive liver cirrhosis, but patients show common symptoms like hydrops fetalis, dysmorphic features, liver dysfunction (cirrhosis), hemolytic anemia with renal involvement, and heart problems. The biochemical profile indicates an elevated level of erythritol, arabitol, ribitol, sedoheptitol, perseitol, sedoheptulose, mannoheptulose, and sedoheptulose-7P. The disorder is caused by mutations in the TALDO gene.","Inherited metabolic disease"
"H02368","Developmental delay with short stature, dysmorphic facial features, and sparse hair","Developmental delay with short stature, dysmorphic facial features, and sparse hair (DEDSSH) is an autosomal recessive intellectual disability with short stature, craniofacial and ectodermal anomalies. It has been reported that DPH1 is responsible gene for DEDSSH.","Congenital malformation"
"H01519","Scabies","Scabies is a disease caused by the ectoparasitic mite Sarcoptes scabiei. Scabies is a contagious cutaneous inflammation and common among many different species of animals. S. scabiei burrows into the skin of their host, reproducing and laying eggs in the burrows. Transmission of the mite commonly occurs by skin-to-skin contact, but with crusted scabies it may also occur through fomites, such as infected clothing or bedding.","Infectious disease"
"H01941","Glycogen storage disease type III","Glycogen storage disease type III (GSD-III), also known as Cori disease or Forbes disease, is an autosomal recessive disorder of glycogen metabolism caused by deficient activity of glycogen debranching enzyme AGL. Most GSD-III patients have AGL deficiency in both the liver and muscle (type IIIa), but some have it in the liver but not muscle (type IIIb).","Inherited metabolic disease"
"H00893","Skin fragility-woolly hair syndrome","Skin fragility-woolly hair syndrome is a rare autosomal recessive genodermatosis caused by defective desmoplakin, an important desmosomal plaque protein. Patients with skin fragility-woolly hair syndrome present with symptoms including focal and diffuse palmoplantar keratoderma, woolly hair, varying degrees of alopecia, and dystrophic nails. Unlike other disorders associated with desmoplakin mutation, no cardiac symptoms are reported in this disease.","Congenital malformation"
"H00052","Clear cell sarcoma of soft tissue","Soft tissue sarcomas account for only about 1% of all malignant diseases and there are less than 8,700 new cases per year in the United States. Clear cell sarcoma (CCS), a highly malignant tumor of deep soft tissues is perhaps the rarest of these. CCS is characterized by the translocation t(12;22)(q13;q12). This translocation rearranges the ATF1 gene at 12q13 and the EWSR1 gene at 22q12, originating an EWSR1/ATF1 fusion gene. Given its specificity, this genetic aberration is considered pathognomonic for CCS and can be used as a diagnostic marker of this neoplasia.","Cancer"
"H01180","Sveinsson chorioretinal atrophy (SCRA)","Sveinsson chorioretinal atrophy (SCRA), also referred to as helicoid peripapillary chorioretinal degeneration (HPCD), is a distinct autosomal dominant disease affecting both eyes characterized clinically by bilateral, well defined, tongue-shaped strips of atrophic retina and choroid that extend from the optic nerve into the peripheral ocular fundus. The lesions may be evident at birth and usually progress throughout life, sometimes leading to central visual loss. Clinical findings suggest that the expansion of the degenerative lesions is caused by dysplastic abnormalities of the peripapillary retinal pigment epithelium (RPE) and the mechanical tearing of the RPE layer owing to the growth of the globe. Patients with SCRA have a mutation in the TEAD1 gene.","Nervous system disease"
"H00260","Pigmented micronodular adrenocortical disease","Primary pigmented micronodular adrenocortical disease (PPNAD) is a form of ACTH-independent adrenal hyperplasia resulting in endogenous Cushing's syndrome.","Endocrine disease"
"H02153","Megalencephaly-capillary malformation syndrome","Megalencephaly-capillary malformation (MCAP) syndrome is a rare overgrowth syndrome. The main symptoms are progressive megalencephaly, polymicrogyria, capillary malformations, syndactyly, and connective tissue dysplasia. Mutations in PIK3CA have been reported in MCAP patients.","Congenital malformation"
"H00604","Deafness, autosomal dominant","Hereditary deafness is divided into syndromic forms (in which hearing loss is associated with a variety of other anomalies) and non-syndromic forms. Non-syndromic forms are responsible for 70% of the cases of hereditary etiology and syndromic cases represent 30% of them. Among the forms of heritage, autosomal-recessive inheritance is the most frequent one (75%-85%), followed by autosomal-dominant inheritance (12-13%) and X-linked or mitochondrial, with 2-3% of the cases of non-syndromic hearing loss. Autosomal-dominant forms of deafness are usually post-lingual and progressive. Dominant mutations may be consistent with initial function and subsequent hearing loss owing to accumulation of pathology.","Nervous system disease"
"H00436","Osteopetrosis","The osteopetroses are a heterogeneous group of disorders characterized by increased bone density and the replacement of trabecular bone with compact bone due to reduced osteoclastic bone resorption. Some osteopetrotic conditions exhibit additional clinical features including renal tubular acidosis and secondary neurological impairment. In forms of osteopetrosis with normal osteoclast counts, most of the mutated genes encode proteins that regulate the intra- and extracellular pH of osteoclasts, such as TCIRG1 gene encoding for the a3 subunit of the V-ATPase and CLCN7 gene. In cases with decreased osteoclast counts, osteoclast differentiation is impaired by mutations in RANKL or RANK. These RANK-deficient patients could be rescued by hematopoietic stem cell transplantation.","Congenital malformation"
"H02361","Myoclonic-atonic epilepsy","Myoclonic-atonic epilepsy (MAE) is an autosomal dominant disorder caused by mutations in SLC6A1. GAT-1, encoded by SLC6A1, is one of the major gamma-aminobutyric acid (GABA) transporters in the brain and is responsible for reuptake of GABA from the synapse.","Nervous system disease"
"H01722","Galloway-Mowat syndrome","Galloway-Mowat Syndrome (GAMOS) is an autosomal recessively inherited condition characterized by the association of nephrotic syndrome and central nervous system involvement. Several case reports and studies on small series describing the clinical and histopathological features of GAMOS have revealed the clinical heterogeneity of this condition. The consistent morphological hallmark is microcephaly, which is often present at birth (primary microcephaly) but might also develop postnatally (secondary microcephaly). Major brain abnormalities include cerebral atrophy and neural-migration defects, such as agyria, microgyria, or polymicrogyria. These structural brain abnormalities are associated with severe psychomotor impairment, hypotonia, and seizures in half of all cases. The nephrotic syndrome occurs in the first four months of life with an average of three months, and a congenital nephrotic syndrome has rarely been described. This nephrotic syndrome is steroid-resistant and associated with a constant and rapid deterioration of renal function. Death usually occurs within few years from the onset. Very recently, several genes have been identified as the cause of GAMOS.","Congenital malformation"
"H01510","Malignant paraganglioma","Paragangliomas (PGLs) are rare neuroendocrine tumors that arise in sympathetic and parasympathetic paraganglia and derive from neural crest cells. Malignancy is defined by presence of metastases, tumor spread in sites where chromaffin tissue is normally absent such as lymph nodes, liver, lungs, and bones. Malignant PGLs are extremely rare. The pathogenesis and progression of PGLs are very strongly influenced by genetics. A germline mutation in one of the susceptibility genes identified so far explains ~40% of all cases; the remaining 60% are thought to be sporadic cases. Sporadic as well as hereditary PGLs have been divided in two main clusters linked to two different signalling pathways: the first cluster contains all VHL-, SDHx-, and FH- mutated tumors and is associated to the activation of hypoxic pathway, while the second cluster contains all RET- , NF1-, MAX and TMEM127- mutated tumors and is associated to the activation of MAPK and mTOR (mammalian target of rapamycin) signaling pathways.","Cancer"
"H02395","Calvarial doughnut lesions with bone fragility","Calvarial doughnut lesions with bone fragility (CDL) is a rare autosomal dominant skeletal disorder characterized by low-bone mineral density, increased spinal and peripheral fractures, and sclerotic, doughnut-shaped lesions in the cranial bones. Novel heterozygous pathogenic variants in the sphingomyelin synthase 2 gene (SGMS2) has been identified.","Musculoskeletal disease"
"H01948","Glycogen storage disease type IX","Glycogen storage disease type IX (GSD-IX), also known as Phosphorylase kinase deficiency, is a disorder of glycogen metabolism. The liver phosphorylase kinase is a heterotetramer that is composed of four copies each of alpha, beta, gamma, and delta (calmodulin) subunits. In liver, the alpha, beta, and gamma subunits are encoded by the PHKA2 gene, the PHKB gene, and PHKG2 gene respectively. Mutation within these genes has been shown to result in GSD type IX. Presenting symptoms include hepatomegaly, ketotic hypoglycemia, and growth delay. GSD IXd, also known as X-linked muscle glycogenosis, is caused by mutation in the PHKA1 gene, which encodes the alpha subunit of muscle phosphorylase kinase. The typical clinical signs of GSD IXd are exercise intolerance, often combined with cramps, myalgia, weakness or myoglobinuria.","Inherited metabolic disease"
"H01174","Congenital diarrhea","Congenital diarrheas are a group of rare chronic enteropathies characterized by a heterogeneous etiology. In the first weeks of life, patients usually present with severe diarrhea that within a few hours leads to a life-threatening condition secondary to massive dehydration and metabolic acidosis.","Gastrointestinal disease"
"H00294","Dilated cardiomyopathy","Dilated cardiomyopathy (DCM) is a heart muscle disease characterised by dilation and impaired contraction of the left or both ventricles that results in progressive heart failure and sudden cardiac death from ventricular arrhythmia. Genetically inherited forms of DCM ('familial' DCM) have been identified in 25-35% of patients presenting with this disease, and the inherited gene defects are an important cause of 'familial' DCM. The pathophysiology may be separated into two categories: defects in force generation and defects in force transmission. In cases where an underlying pathology cannot be identified, the patient is diagnosed with an 'idiopathic' DCM. Current hypotheses regarding causes of 'idiopathic' DCM focus on myocarditis induced by enterovirus and subsequent autoimmune myocardium impairments. Antibodies to the beta1-adrenergic receptor (beta1AR), which are detected in a substantial number of patients with 'idiopathic' DCM, may increase the concentration of intracellular cAMP and intracellular Ca2+, a condition often leading to a transient hyper-performance of the heart followed by depressed heart function and heart failure.","Cardiovascular disease"
"H01346","Bloom syndrome","Bloom syndrome is a rare autosomal recessive genetic disorder due to mutation in BLM (RecQ protein-like 3). This disease is characterized by severe growth deficiency, an erythematous and photosensitive facial rash, dysmorphic features such as microcephaly and malar hypoplasia, immunodeficiency and a high predisposition to various types of cancer. The function of BLM as a helicase and its role during the regulation of homologous recombination (HR) is well characterized. Recently, the role of BLM as a DNA damage sensor has been revealed.","Congenital malformation"
"H00409","Type 2 diabetes mellitus","Type 2 diabetes mellitus (T2DM) is characterized by chronic hyperglycemia due to insulin resistance of peripheral tissues (skeletal muscle, liver, adipose tissue) and insufficient compensatory insulin secretion by pancreatic beta cells. Both insulin resistance and beta cell dysfunction are thought to result from the complex interplay of many different pathways under the combined control of environmental and genetic factors. It is accepted that T2DM results from population aging and adverse environmental factors of the modern world which favor the development of obesity.","Metabolic disease; Endocrine disease"
"H00851","Proximal symphalangism","Proximal symphalangism (SYM) is an autosomal-dominant condition characterized by variable fusion of the proximal interphalangeal joints.","Congenital malformation"
"H01983","Carnitine-acylcarnitine translocase deficiency","Carnitine-acylcarnitine translocase (CACT) is located in the inner mitochondrial membrane and operates a carnitine-acylcarnitine exchange across this membrane. It is one of the key enzymes for transporting long-chain fatty acids into mitochondria. CACT deficiency is clinically characterized by life-threatening non-ketotic hypoglycemia and rhabdomyolysis.","Inherited metabolic disease; Mitochondrial disease"
"H01379","Arcobacter butzleri infection","Arcobacter butzleri is the best characterized of all Arcobacters and an emerging pathogen causes diarrhea, recurrent abdominal cramps and bacteremia. A. butzleri is isolated often from aqueous environments, multiple animals and food sources. In recent years, there is an increase in isolation from human diarrheal stool samples.","Infectious disease"
"H01977","Laing distal myopathy","Laing distal myopathy (MPD1) is an early onset autosomal dominant distal myopathy. Selective weakness of the anterior tibial muscles is followed by weakness of the finger extensors and of selected proximal muscle groups, such as the abductors and rotators. This disease is caused by mutations in MYH7, the gene encoding the myosin heavy chain, which is expressed in type 1 fibers of skeletal muscle and in the heart.","Nervous system disease; Musculoskeletal disease"
"H00099","Leukocyte adhesion deficiency","Leukocyte adhesion deficiency (LAD) is a rare, autosomal recessive genetic disorder in which neutrophils fail to mobilize and migrate to sites of injury. At least three genetically distinct forms of this group of disorders have been described: LAD I, II, and III. Defects in the expression of beta2-integrins and fucose- containing proteins account for LAD-I and LAD-II, respectively. In LAD-III integrin expression by leukocytes is normal, but the integrins fail to generate high avidity for their cognate endothelial-cell ligands. Mutations in the KINDLIN3 (official symbol FERMT3), a gene that encodes an intracellular protein that interacts with cytoplasmic tails of beta-integrins in hematopoietic cells, is the cause of LAD-III. Dominant-negative mutations resulting in deficiency of ras-related C3 botulinum toxin substrate (Rac2), the predominant hematopoeitic-specific Rho GTPase in neutrophils also leads to leukocyte adhesion deficiency.","Primary immunodeficiency"
"H02198","Pancreatic agenesis and congenital heart disease","Pancreatic agenesis and congenital heart disease is a rare autosomal dominant disorder characterized by neonatal diabetes with pancreatic hypoplasia and congenital heart disease. Mutations in GATA6 has been linked to this disease. GATA6 is expressed during the embryogenesis of a variety of endodermally derived organs, including the heart, pancreas, ovary, lung, and liver.","Congenital malformation"
"H00293","Arrhythmogenic right ventricular cardiomyopathy","Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease that may result in arrhythmia, heart failure, and sudden death. The hallmark pathological findings are progressive myocyte loss and fibrofatty replacement, with a predilection for the right ventricle. A number of genetic studies have identified mutations in various components of the cardiac desmosome that have important roles in the pathogenesis of ARVC. Disruption of desmosomal function by defective proteins might lead to death of myocytes under mechanical stress. The myocardial injury may be accompanied by inflammation. Since regeneration of cardiac myocytes is limited, repair by fibrofatty replacement occurs. Several studies have implicated that desmosome dysfunction results in the delocalization and nuclear translocation of plakoglobin. As a result, competition between plakoglobin and beta-catenin will lead to the inhibition of Wnt/beta-catenin signaling, resulting in a shift from a myocyte fate towards an adipocyte fate of cells. The ryanodine receptor plays a crucial part in electromechanical coupling by control of release of calcium from the sarcoplasmic reticulum into the cytosol. Therefore, defects in this receptor could result in an imbalance of calcium homeostasis that might trigger cell death.","Cardiovascular disease"
"H01341","Collagen VI myopathy","Collagen VI-related myopathy include severe Ullrich congenital muscular dystrophy (UCMD) and milder Bethlem myopathy. Mutations in each of the three collagen VI genes COL6A1, COL6A2, and COL6A3 cause these diseases. Recently, an additional phenotypes, autosomal recessive myosclerosis with mutations in COL6A2 have been reported. Collagen VI is an important component of the extracellular matrix which forms a microfibrillar network that is found in close association with the cell and surrounding basement membrane. Thus, collagen VI mutations result in disorders with combined muscle and connective tissue involvement, including weakness, joint and contractures, and abnormal skin findings.","Nervous system disease; Musculoskeletal disease"
"H01173","Stiff skin syndrome","Stiff skin syndrome (SSS) is an autosomal dominant congenital form of scleroderma characterized by stony-hard skin, limitation of joint mobility, and mild hypertrichosis, remarkable in the areas with abundant fascia on the thighs and buttocks. SSS is caused by mutations in the Arg-Gly-Asp (RGD) sequence-encoding domain of fibrillin-1 that mediates integrin binding.","Skin and connective tissue disease"
"H01517","Erysipelas","Streptococcus pyogenes (group A Streptococcus) is the usual etiologic agent of erysipelas. Symptoms and signs of erysipelas are chills, fever, a well-demarcated, erythematous, indurated, rapidly spreading patch with a palpable advancing border on the face or extremities. This disease most frequently affects infants, small children and the elderly.","Infectious disease"
"H02392","Scedosporiosis","Scedosporiosis caused by the genus Scedosporium has emerged as a severe infection in both immunocompromised and immunocompetent individuals with a high incidence, ranging from localized to disseminated infections worldwide. Infectious agents are ubiquitous filamentous fungi present in soil, sewage, and polluted waters. Scedosporium apiospermum is the most common agent of scedosporiosis. Infection is acquired through trauma, inhalation and near-drowning.","Infectious disease"
"H01725","Primary immunodeficiency disease","Primary immunodeficiency diseases (PIDs) are genetically determined disorders of the immune system resulting in greatly enhanced susceptibility to infectious disease, autoimmunity and malignancy. Many are associated with single gene defects, whereas others may be polygenic or may represent interactions of genetically determined characteristics with environmental or infectious stresses. There are more than 150 different disorders which have been described till date. PIDs are broadly classified as disorders of adaptive immunity (i.e., T-cell, B-cell or combined immunodeficiencies) or of innate immunity (e.g., phagocyte and complement disorders). Early diagnosis and treatment are imperative for preventing significant disease-associated morbidity.","Immune system disease"
"H00431","Ossification of the posterior longitudinal ligament of spine","Ossification of the posterior longitudinal ligament of spine (OPLL) is an osteogenetic disorder of the spine found among Japanese and other East Asian populations. Ectopic bone formation in the posterior longitudinal ligaments causes myelopathy in patients with OPLL. Genetic linkage studies revealed genes encoding collagens, nucleotide pyrophosphatase, and TGF-beta3 in association with susceptibility to the disease.","Musculoskeletal disease"
"H02366","Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome","Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) is an adult-onset, slowly progressive neurological disorder characterized by imbalance, sensory neuropathy, bilateral vestibulopathy, and chronic cough. Biallelic expansion of an intronic repeat in RFC1 is a cause of CANVAS.","Nervous system disease"
"H02154","Omodysplasia","Autosomal recessive omodysplasia (OMOD1) is a genetic condition characterized by short-limbed short stature, craniofacial dysmorphism, and variable developmental delay. It is caused by mutations in glypican 6 (GPC6). An autosomal dominant form (OMOD2) involving only the upper limbs was later recognized as a separate disorder.","Congenital malformation"
"H00603","Hypertension exacerbated in pregnancy","'Hypertension exacerbated by pregnancy' is a syndrome similar to Apparent mineralocorticoid excess (AME) with autosomal dominant early-onset hypertension. The affected individuals have a gain of function mutation in the human mineralocorticoid receptor (MR), resulting in constitutively stimulated Na reabsorption. Hypertension is present in nonpregnant patients and may be severe, but the characteristic feature is marked worsening during pregnancy. The proposed explanation is that the mutation renders the receptor sensitive to nonmineralocorticoid steroids such as progesterone, the level of which rises 100-fold during pregnancy.","Cardiovascular disease"
"H00267","Holoprosencephaly","Holoprosencephaly (HPE) is characterized by incomplete separation of forebrain and facial components into left and right sides.","Congenital malformation"
"H00869","Leukoencephalopathy with vanishing white matter","Leukoencephalopathy with vanishing white matter (VWM), also referred to as childhood ataxia with diffuse central nervous system hypomyelination (CACH), is one of the most prevalent inherited childhood disorders of cerebral white matter. This autosomal recessive progressive neurological disorder usually begins in early childhood, but a wide spectrum of clinical severity is now recognized from fatal infantile forms such as Cree leukoencephalopathy to mild later-onset forms associated with ovarian failure. The principal findings are cerebellar ataxia and spasticity with relative preservation of mental abilities. Nearly all patients have mutations in any of the 5 genes encoding the eukaryotic translation initiation factor eIF2B. Mutated eIF2B could impair the ability of cells to regulate protein synthesis, especially under conditions of cell stress.","Nervous system disease; Congenital disorder of metabolism"
"H00055","Laryngeal cancer","Laryngeal cancer is one of the most common malignancies in Europe, with about 52,000 new cases per year, 90% of them occurring in men. Smoke and alcohol represent the major behavioral risk factors. Of all laryngeal cancers, some 95% are squamous cell carcinomas. Some molecular events have been described in laryngeal squamous cell carcinoma (LSCC). Although tumor suppressor inactivation of p53 and p16 is common in these tumors (about 50% each), oncogenic activation is less well characterized. Cyclin D1 and epidermal growth factor receptor amplification have been reported in one-third and one-quarter of LSCCs, respectively, both related to advanced stages, whereas c-myc could be amplified in 13% of cases although without associated overexpression.","Cancer"
"H01187","Tietz syndrome","Tietz syndrome is an autosomal dominant syndrome of hypopigmentation and deafness. A missense mutation has been found in the basic region of the MITF (microphthalmia associated transcription factor) gene. Mutations in other regions of this gene have been found to produce Waardenburg syndrome type 2 (WS2) [DS:H00169], which also includes pigmentary changes and hearing loss, but in contrast to Tietz syndrome, depigmentation is patchy and hearing loss is variable in WS2.","Skin disease"
"H01528","Neuroleptic malignant syndrome","Neuroleptic malignant syndrome (NMS) is a rare but potentially life-threatening sideeffect to antipsychotic drugs characterized by fever, altered mental status, muscle rigidity, and autonomic dysfunction. NMS is classically associated with the use of high-potency antipsychotics (AP), such as butyrophenones and phenothiazines, but has also been described with newer agents, commonly described as atypical AP (risperidone, olanzapine, quetiapine), other D2-receptor antagonists (metoclopramide), and following withdrawal of anti dopaminergic agents. Although the precise pathophysiologic mechanism underlying NMS remains unknown, a reduction in dopaminergic activity in the brain probably by dopamine D2 receptor blockade in the striatum and hypothalamus is generally assumed as a potential cause. Laboratory findings include elevation of serum creatine phosphokinase (CK), liver enzymes, and leukocitosis. Treatment includes immediately stopping the offending agent and implementing supportive measures, as well as pharmacological interventions in more severe cases.","Nervous system disease"
"H01970","Lymphoproliferative syndrome 1","Lymphoproliferative syndrome 1 is a severe autosomal recessive lymphoproliferative disease, associated with Epstein-Barr virus. ITK mutations were identified as the cause for this disease. Common immunological features are a progressive hypogammaglobulinemia and a progressive loss of CD4+ T cells with a declining proportion of naive T cells.","Primary immunodeficiency"
"H00856","Distal hereditary motor neuropathies","Distal hereditary motor neuropathies (dHMN) comprise a heterogenous group of diseases that share the common feature of a length-dependent predominantly motor neuropathy. Many forms of dHMN have minor sensory abnormalities and/or a significant upper-motor-neuron component, and there is often an overlap with the axonal forms of Charcot-Marie-Tooth disease (CMT) [DS:H00264] and with juvenile forms of amyotrophic lateral sclerosis [DS:H00058] and hereditary spastic paraplegia [DS:H00266]. The causative genes with autosomal dominant, recessive, and X-linked patterns of inheritance have implicated proteins with diverse functions. Distal HMN are classified into phenotypic subtypes according to age at onset, mode of inheritance, and presence of additional features.","Nervous system disease"
"H01984","Leopard syndrome","LEOPARD syndrome is an autosomal dominant developmental disorder belonging to a relatively prevalent class of inherited RAS-MAPK signalling diseases. Its main features are lentigines, electrocardiographic abnormalities, ocular hypertelorism, pulmonary valve stenosis, abnormal genitalia, retardation of growth and deafness. Approximately 90% of LEOPARD syndrome cases are caused by missense mutations in the PTPN11 gene which encodes the protein tyrosine phosphatase SHP2. But it may also be caused by mutations in RAF1 or BRAF.","Congenital malformation"
"H00258","Aldosterone synthase deficiency","Aldosterone synthase deficiency is an autosomal recessive disorder caused by a defect in the final biochemical step of aldosterone biosynthesis, the 18-hydroxylation of 18-hydroxycorticosterone to aldosterone. This disease is characterized by life-threatening salt-loss, failure to thrive, hyponatraemia and hyperkalaemia in early infancy. In type I deficiency, aldosterone is undetectable, whereas in type II aldosterone can be low or normal.","Endocrine disease"
"H02359","Dejerine-Sottas disease","Dejerine-Sottas disease (DSD), also known as Charcot-Marie-Tooth disease type 3, is a severe, demyelinating neuropathy, presenting in infancy with delayed motor development, very slow nerve conduction velocities and elevated CSF protein. Progression is severe and walking ability is lost early. Hypomyelination and classic onion bulbs are the pathological hallmarks. Mutations in MPZ, PMP22, EGR2, and PRX are the most common causes of DSD. In more than 50% of cases, a causative genetic mutation cannot be identified.","Nervous system disease"
"H02019","Familial male-limited precocious puberty","Familial male-limited precocious puberty, also known as familial testotoxicosis is a form of isosexual precocious puberty in boys in which testosterone levels are elevated independent of changes in luteinizing hormone-releasing hormone and serum luteinizing hormone levels. Activating mutations in the human luteinizing hormone receptor (hLHR) have been described.","Endocrine disease"
"H00118","Congenital disorders of glycosylation type I","Congenital disorders of glycosylation (CDG) are a group of disorders caused by defects in various genes for N-glycan biosynthesis. CDG type I is defined by mutations in genes encoding enzymes which involves disrupted synthesis of the lipid linked oligosaccharide precursor and its transfer to polypeptide chain of protein, affecting N-glycan assembly in cytosol and endoplasmic reticulum. An increasing number of disorders have been discovered, with many subtypes identified. PMM2-CDG is the most common form, with over 800 patients diagnosed mostly in Europe. Almost all type present in infancy. These diseases demonstrate a broad range of clinical manifestation, associated with developmental delay, psychomotor retardation, hypotonia, seizures, hepatomegaly, microcephaly, and pericardial effusion.","Inherited metabolic disease"
"H00924","Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation","Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation is a syndrome associated with T and B cell-combined lymphocytopenia, growth retardation, microcephaly, and increased cellular radiosensitivity. Mutations in human NHEJ1 can lead to lymphocytopenia due to its role in V(D)J recombination in the immune system. This disease shows features common with the ones observed in LIG4 deficiency or Nijmegen breakage syndrome.","Primary immunodeficiency"
"H01802","Pulmonary atresia with intact ventricular septum","Pulmonary atresia with intact ventricular septum (PAIVS) is a severe cardiac malformation characterized by variable right ventricular development and imperforate pulmonary valve. PAIVS has a wide spectrum of clinical presentation ranging from cyanosis to shock due to closure of ductus arteriosus. The treatment follows initial stabilization with prostaglandin and establishment of antegrade flow. Because of the morphologic heterogeneity, repair or palliation strategies vary widely, ranging from single ventricle palliation to complete biventricular repair. Overall, regardless of anatomical subtype, survival is poor, reported to be as low as 50% at 5 years.","Developmental disorder; Cardiovascular disease"
"H02489","Mild encephalopathy with reversible myelin vacuolization","Mild encephalopathy with reversible myelin vacuolization (MMERV) is a familial disorder with clinical finding of mild encephalitis/encephalopathy with a reversible splenial lesion (MERS). Mutations in MYRF have been identified in patients. MYRF is a critical transcriptional regulator required for CNS myelination.","Nervous system disease"
"H01668","Neoplastic meningitis","Neoplastic meningitis (NM) is a diffuse dissemination of tumor cells into the cerebrospinal fluid (CSF) and/or leptomeninges. NM is reported in patients with solid tumours (carcinomatous meningitis), haematological malignancies (leukaemic or lymphomatous meningitis), or primary brain tumours. Malignant cells reach the CSF and meninges by direct invasion from tumors located near or within the central nervous system (CNS), or via the bloodstream or other pathways that contact the CNS. The molecular changes responsible for the development of NM are not well delineated, but it is likely that they involve changes in molecules responsible for tumor cell adhesion, migration, and proliferation.","Nervous system disease"
"H00588","Kindler syndrome","Kinder syndrome is a rare autosomal recessive disease characterized by blister, poikiloderma, skin atrophy, and photosensitivity.","Skin disease"
"H02442","Common cold","The common cold is a viral infection of the upper respiratory tract. Many types of viruses can cause a common cold, with rhinoviruses being the most common. Certain coronaviruses are also implicated in causing a common cold.","Infectious disease"
"H00315","Gonococcal infection","Gonorrhea is an ancient disease caused by the strict human pathogen Neisseria gonorrhoeae. It remains a major public health concern and multidrug-resistant forms of gonorrhea have been discovered.","Infectious disease"
"H00127","Metachromatic leukodystrophy","Metachromatic leukodystrophy (MLD) is an autosomal recessive demyelinating lysosomal storage disease caused by deficiency of lysosomal arylsulfatase A (ARSA). The enzyme defect results in the accumulation of sulfatide in the central and peripheral nervous systems and extensive white matter damage and loss of both cognitive and motor functions. Mutated PSAP gene resulting in sphingolipid activator protein B deficiency is known to cause MLD variant in which ARSA is normal.","Inherited metabolic disease; Lysosomal storage disease; Nervous system disease"
"H01491","Neuromyelitis optica","Neuromyelitis optica (NMO), also known as Devic's disease is an inflammatory demyelinating disease that selectively affects optic nerves and spinal cord. The etiology of NMO is unknown but it is believed to be an autoimmune disorder triggered by an environmental factor, possibly an infection, in genetically susceptible individuals. The principal effector in NMO is the self-reactive, complement-activating anti-AQP4 antibody. AQP4 water channel is a component of the dystroglycan protein complex located in astrocytic foot processes at the blood-brain barrier. Anti-AQP4 antibody is sensitive and highly specific serum markers of autoimmune NMO. For many decades, NMO was considered to be a subtype of multiple sclerosis (MS), but prognosis and optimal treatments differ. Corticosteroids and plasma exchange (PLEX) are the most commonly used therapeutic modalities in acute settings. Corticosteroids exert global immunosuppressive and anti-inflammatory effects, whereas PLEX removes antibodies, complement, and cytokines from the blood. Besides, immunosuppressant agents interfering with the function of T and B cells have been shown to prevent disease relapses and reduce neurological disability in NMO.","Immune system disease; Nervous system disease"
"H00543","Renal-hepatic-pancreatic dysplasia","Renal-hepatic-pancreatic dysplasia is a rare lethal disorder characterized by pancreatic cyst formation in addition to the combination of renal dysplasia and hepatic fibrosis. NPHP3-null mutations cause the disorder.","Congenital malformation"
"H02214","Familial focal epilepsy with variable foci","Familial focal epilepsy with variable foci (FFEVF) is an autosomal dominant form of epilepsy characterized by focal seizures arising from different cortical regions, including the temporal, frontal, parietal, and occipital lobes. Recently, it has been identified that mutations in the mTOR pathway regulators, DEPDC5, NPRL2 and NPRL3 cause this disease.","Nervous system disease"
"H02026","Familial hypocalciuric hypercalcemia","Familial hypocalciuric hypercalcemia (HHC), an autosomal dominant disorder, is characterized by lifelong elevations of serum calcium concentrations with low urinary calcium excretion. HHC is a genetically heterogeneous disorder with three variants. HHC1 is due to loss-of-function mutations of the calcium-sensing receptor. HHC2 is due to mutations in GNA11. HHC3 is associated with AP2S1 mutations, which result in altered calcium-sensing receptor endocytosis.","Congenital disorder of metabolism"
"H00771","Inherited erythromelalgia","Inherited erythromelalgia (IEM) is characterized by intense episodic burning pain associated with redness and warmth of the affected extremities and in many instances occurs as an autosomal dominant trait. Symptoms of IEM can start as early as 1 year old (early-onset), or in adults (adult-onset), and both types have been described in families and in sporadic cases. Pharmacotherapy has been largely ineffective, and partial relief of symptoms comes from cooling the affected extremities. Dominantly inherited gain-of-function mutations in SCN9A, the gene encoding Nav1.7, cause IEM.","Vascular disease"
"H01465","Large-vessel vasculitis","Large vessel vasculitis (LVV) covers a spectrum of primary vasculitides predominantly affecting the aorta and its major branches. Giant cell arteritis (GCA) and Takayasu arteritis (TAK) are the two main subtypes. GCA is the most common vasculitis affecting adults aged 50 years or more, while TAK is a rare vasculitis that affects younger individuals mainly under 40 years. Clinical presentations vary from asymptomatic to significant systemic symptoms such as fever, weight loss, and symptoms that result from aortitis and high inflammatory markers; C-reactive protein (CRP); and erythrocyte sedimentation rate (ESR) levels. Glucocorticoids are the mainstay of therapy of LVV. Patients may develop predictable adverse effects from long-term glucocorticoid use.","Nervous system disease; Cardiovascular disease"
"H01657","Nephrotic syndrome","Nephrotic syndrome is a heterogeneous group of disorders characterized by heavy proteinuria (more than 3.5 grams per day), hypoalbuminemia, hyperlipidemia, and edema. Congenital nephrotic syndrome is most frequently related to mutations in genes specific for structural integrity of the glomerular basement membrane and associated filtration structures within the kidney, resulting in massive leakage of plasma proteins into the urine. First line treatment is with oral corticosteroids, but some patients do not respond to this treatment. Steroid-resistant nephrotic syndrome (SRNS) typically manifests histologically as focal segmental glomerulosclerosis. Calcineurin inhibitors with/without intravenous methylprednisolone pulse therapy (MPT) constitute the standard treatment for SRNS. It has been reported that additional rituximab treatment combined with conventional MPT and immunosuppressive agents is a promising option.","Urinary system disease"
"H00785","Congenital hypotrichosis with juvenile macular dystrophy","Hypotrichosis with juvenile macular dystrophy is a rare autosomal recessive disorder characterized by sparse scalp hair from birth and resulting hair loss associated with progressive macular degeneration leading to blindness not later than the third decade of life. The causative gene is CDH3 encoding P-cadherin.","Congenital malformation"
"H01233","Urocanase deficiency","Urocanase deficiency is an autosomal recessive disoder of histidine metabolism caused by mutations in the UROC1 gene. It is characterized by mental retardation, urocanic aciduria, and a defective activity of urocanase of the liver. Patients sometimes display ataxia.","Inherited metabolic disease"
"H01001","COACH syndrome","COACH syndrome is a rare autosomal recessive disorder with cerebellar vermis hypoplasia, oligophrenia, ataxia, coloboma, and hepatic fibrosis. The vermis hypoplasia comprises a part of a spectrum of mid-hindbrain malformation called the 'molar tooth sign' that is characteristic to Joubert syndrome.","Congenital malformation"
"H01039","Ovarian hyperstimulation syndrome","Ovarian hyperstimulation syndrome (OHSS) is typically an iatrogenic complication of ovulation induction (OI) occurring during the luteal phase or early pregnancy. OHSS is characterised by a cystic enlargement of the ovaries and an acute fluid shift from the intravascular to the third space, which may result in ascites, pleural infusions, pericardial infusion, and even generalized edema. Majority of OHSS cases have been associated with the use of gonadotrophins for OI in anovulatory women or for ovarian stimulation (OS) in the context of assisted reproductive technology (ART). Recurrent cases and familial occurrence of OHSS have been described, and different mutations in the follicle-stimulating hormone receptor (FSHr) have been reported in these cases. Polycystic ovarian syndrome (PCOS) appears to be the major predisposing factor for OHSS in a large number of studies.","Reproductive system disease"
"H01805","Tricho-hepato-enteric syndrome","Tricho-hepato-enteric syndrome (THE), also known as syndromic diarrhea (SD), is a congenital enteropathy presenting with early-onset severe intractable diarrhea and associated with non-specific villous atrophy with low or no mononuclear cell infiltration of the lamina propria nor specific histological abnormalities involving the epithelium. Infants are born small for gestational age. Patients present with facial dysmorphism, immune disorders and, in some patients, early onset of severe liver cirrhosis. It has been linked to abnormalities in two components of the putative human ski complex: SKIV2L and TTC37. During their clinical course, most of the patients require parenteral nutrition and often immunoglobulin supplementation.","Congenital malformation"
"H00923","Congenital systemic glutamine deficiency","Congenital systemic glutamine deficiency (CSGD) is a rare developmental disorder with severe brain malformation resulting in multi-organ failure and neonatal death. Glutamine synthetase plays a major role in ammonia detoxification, interorgan nitrogen flux, acid-base homeostasis, and cell signaling. It has been reported that glutamine was largely absent from affected patients serum, urine, and cerebrospinal fluid.","Inherited metabolic disease"
"H00749","Episodic ataxias","Episodic ataxias (EAs) are a group of rare autosomal-dominant diseases characterized by recurrent, discrete episodes of ataxia, giddiness, and vertigo. EA1 and EA2 are the most widely recognized of the autosomal-dominant EAs and are caused by dysfunction of neuronal voltage-gated ion channels. There are central and peripheral nervous system manifestations in both conditions. The current classification is based on genetics and actually includes seven distinct subtypes. But these variants other than EA1 and EA2 are rare, some only occurring in single families, and gene mutations have not been identified in all. It is quite likely, however, that the number of phenotypes and mutated genes will grow further.","Nervous system disease"
"H01006","Hereditary angioedema","Hereditary angioedema (HAE) is a rare genetic disorder, manifested by recurrent episodes of angioedema localized to the skin or mucosa of the gastrointestinal tract or larynx. The laryngeal angioedema is potentially lethal. The classic forms, HAE types I and II, result from deficiency of the plasma protease inhibitor, C1 inhibitor (C1INH). Type I HAE is caused by decreased expression of C1INH in the plasma whereas type 2 HAE, consisting approximately 15% of patients with HAE, is due to expression of a dysfunctional C1INH protein. HAE type III has been observed exclusively in women and appears to be correlated with high estrogen levels.","Vascular disease"
"H01234","Trimethylaminuria","Trimethylaminuria (TMAU), also known as fish odour syndrome, is a metabolic disorder. TMAU usually presents with a body odour resembling that of rotten or decaying fish, the result of excess excretion of trimethylamine (TMA) in the breath, sweat, urine, and reproductive fluids. Primary TMAU is most often caused by a functional defect of flavin mono-oxygenase 3 (FMO3), and the genetic disorder is inherited in an autosomal recessive manner as a consequence of mutations in the FMO3 gene. Secondary TMAU has been described in patients with severe liver disease (which is the major site of activity of the FMO3 enzyme) and chronic renal disease (as a consequence of bacterial overgrowth in the gut), and in patients treated with large doses of betaine or possibly L-carnitine. In addition, transient TMAU has been reported in a preterm infant who was fed with choline-rich food supplements and has been reported in some women just at the onset of menstruation.","Inherited metabolic disease"
"H01650","Pemphigoid","Pemphigoid diseases are group of autoimmune blistering disorders of the skin and mucous membranes characterized by autoantibodies directed against structural proteins of the dermal-epidermal junction that clinically can manifest with urticarial lesions, tense blisters, and erosions which may involve the mucous membranes. Diseases in this group include bullous pemphigoid (BP), dermatitis herpetiformis, mucous membrane pemphigois, linear IgA bullous dermatosis, herpes gestationis, and epidermolysis bullosa acquisita. BP is the most common acquired bullous autoimmune dermatosis disease. It is primarily a disease of the elderly with an equal incidence in men and women. The clinical characteristics are the formation of tense blisters and pruritic urticarial erythema. Histopathologically, subepidermal blister formation associated with eosinophil infiltration is commonly observed in BP. The main autoantigens targeted by BP autoantibodies are hemidesmosomal transmembrane collagen XVII (COL17, also known as BP180/BPAG2) and the intracytoplasmic plakin family protein BP230. Most of these antibodies belong to the immunoglobulin G class. Diagnosis of BP relies on the clinical and histological aspects, but the most reliable clues are given by direct and indirect immunofluorescence. Three types of drugs, with distinct mechanisms of action, are used to treat BP: anti-inflammatory drugs, drugs designed to reduce the production of pathogenic antibodies, and treatments that increase the elimination of pathogenic antibodies from the serum of patients, such as high-dose intravenous immunoglobulin (IVIG) therapy and therapeutic plasma exchange.","Skin and connective tissue disease; Immune system disease"
"H00782","Hypotrichosis and recurrent skin vesicles","Hypotrichosis and recurrent skin vesicles is a condition with sparse and fragile hair on scalp and vesicles on the skin over the body. Desmocollin 3, a transmembrane component of desmosomes, is associated with the disease.","Skin disease"
"H01462","Rapidly growing mycobacteria infection","Nontuberculous mycobacteria (NTM) are classified into 2 categories: slow-growing mycobacteria (SGM) and rapidly-growing mycobacteria (RGM), based on interval to colony formation by subculture on solid media. More than 50 species of RGM have been identified, more than a third of which are opportunistic human pathogens. The most frequently encountered RGM that cause human infections are Mycobacterium abscessus, Mycobacterium chelonae, Mycobacterium fortuitum (complex), Mycobacterium mucogenicum, and Mycobacterium neoaurum. RGM, generally of low virulence, are capable of causing a wide spectrum of infections. Many RGM species, well-known and recently described species, caused significant infections in patients with cancer, including catheter-related bacteremia, disseminated infection, bronchopulmonary infections, dermatitis, cellulitis, and others.","Infectious disease"
"H02021","Chediak-Higashi syndrome","Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disorder characterized by partial skin and ocular albinism, increased susceptibility to infections, and progressive neuropathy. Clinical reports of CHS have identified mutations in the CHS1/LYST gene.","Primary immunodeficiency"
"H00776","Congenital motor nystagmus (CMN)","Nystagmus is an eye movement disorder in which one or both eyes are in constant movement. Nystagmus that occur independent of these known ocular or systemic diseases is referred to as congenital motor nystagmus (CMN) or idiopathic congenital nystagmus (ICN). It can be inherited as an autosomal dominant, an autosomal recessive, or an X-linked trait. At least six genetic loci for CMN have been suggested, including three loci for autosomal dominant CMN, and three loci for X-linked CMN. A variety of mutations in the FRMD7 gene have been identified in many families with an X-linked recessive pattern. Another mutation associated with X-linked CMN is GPR143.","Nervous system disease"
"H01496","Spondyloocular syndrome","Spondyloocular syndrome (SOS) is a rare autosomal recessive disorder due to mutations in the XYLT2 gene. XYLT2 encodes xylosyltransferases involved in proteoglycan biosynthesis. The affected individuals were found to produce lower amount of chondroitin and heparan sulfate. Clinically, the major features include crystalline lens malformation, cataract, retinal detachment that result in loss of vision, facial dysmorphism, generalized osteoporosis, and immobile spine and platyspondly.","Congenital malformation"
"H00544","Septo-optic dysplasia","Septo-optic dysplasia is a heterogeneous condition with optic nerve hypoplasia, dysgenesis of the septum pellucidum, and pituitary hypofunction.","Congenital malformation"
"H02213","Familial adult myoclonic epilepsy","Familial adult myoclonic epilepsy (FAME), also known as benign adult familial myoclonic epilepsy (BAFME), is an autosomal dominant disorder characterized by adult-onset tremulous hand movement, infrequent epileptic seizure and non-progressive course without cerebellar ataxia and dementia. It has been suggested that abnormal expansions of TTTCA and TTTTA repeats in introns of SAMD12, TNRC6A and RAPGEF2 cause this disease. Recently, Autosomal recessive form with a mutation in CNTN2 gene has been reported.","Nervous system disease"
"H00120","Muscular dystrophy-dystroglycanopathy type A","Muscular dystrophies due to reduced glycosylation of alpha-dystroglycan have emerged as a common group of conditions, now referred to as dystroglycanopathies. The phenotypic severity of dystroglycanopathy patients is extremely variable. At the most severe end of the clinical spectrum are Walker-Warburg syndrome (WWS), Muscle-eye-brain disease (MEB), and Fukuyama congenital muscular dystrophy (FCMD). These are termed muscular dystrophy-dystroglycanopathy type A (MDDGA), and characterized by congenital muscular dystrophy with severe structural brain and eye abnormalities, which in WWS results in early infantile death.","Congenital disorder of metabolism; Congenital malformation"
"H02445","Microcornea, myopic chorioretinal atrophy, and telecanthus","Microcornea, myopic chorioretinal atrophy, and telecanthus (MMCAT) is a syndrome caused by mutations in ADAMTS18. ADAMTS18 encodes a member of a family of metallo-proteases that are known for their role in extracellular matrix remodeling. It is suggested that ADAMTS18 plays an essential role in early eye development.","Congenital malformation"
"H00312","Tularemia","Tularemia is a rare zoonotic infection caused by the bacterium Francisella tularensis. It occurs in North America, Europe, and Asia. The most common clinical presentation is ulceroglandular tularemia with chills, fever, head and muscle pain, and prostration. Some people may develop pneumonia or septicemia. Rabbits serve as an important reservoir host for F. tularensis.","Infectious disease"
"H01833","Hemimegalencephaly","Hemimegalencephaly is a rare brain malformation caused by anomalous neuronal and glial proliferation or differentiation, with an abnormally enlarged and dysplastic hemisphere. It can occur as an isolated finding, or as part of a syndrome, such as hypomelanosis of Ito, tuberous sclerosis complex, epidermal nevus syndrome or Klippel-Trenaunay syndrome. Patients have intellectual delay, hemiparesis and severe epilepsy. Drug resistant epilepsy is often treated with a hemispherectomy. If resective surgery is impossible, vagus nerve stimulation (VNS) can be used for seizure palliation. The etiology of hemimegalencephaly is not clear. Some authors consider abnormal neuroepithelial cell lineage as the primary cause.","Congenital malformation"
"H01659","Pityriasis rubra pilaris","Pityriasis rubra pilaris (PRP) is a spectrum of rare chronic inflammatory disorders with papulosquamous eruptions of unknown cause. The prototypical clinical characteristics of PRP are follicular hyperkeratotic papules on an erythematous base that can eventually coalesce to large red plaques. Its classification into five subgroups is based on age at onset, clinical course, morphologic features, and prognosis. More than 50% of patients are best classified as type I with adult-onset PRP. It is comprised of widespread, follicular papules and plaques and tends to clear spontaneously in 80% of patients in one to three years. Type II, which is the atypical adult subtype, tends to be more chronic and presents with areas of alopecia, eczematous patches, and a palmoplantar keratoderma. The classic juvenile type III is observed in only 10% of patients. It is similar clinically to type I but occurs in children and tends to remit in one year. Type IV, which is the circumscribed, juvenile subtype, presents with sharply-demarcated areas of follicular hyperkeratosis and erythema of the elbows and knees. An estimated 5% of children with PRP develop an atypical form classified as juvenile type V. Most familial cases that are published belong to this group. Recently, the designation of a new category of PRP (type VI) has been proposed that is characterized by the presence of HIV infection with different clinical features and a poorer prognosis. Treatment of PRP can be difficult, and no standardized approach has been established, although systemic retinoids are considered first-line therapy. Cyclosporin, methotrexate, and azathioprine are alternatives.","Skin and connective tissue disease"
"H02028","Filariasis","Lymphatic filariasis, onchocerciasis, mansonelliasis and loiasis caused by parasitic roundworms (nematodes) called filariae are diseases of tropical and subtropical countries causing high morbidity.","Infectious disease"
"H00129","Mucopolysaccharidosis type II","Mucopolysaccharidosis type II (MPS2) is an X-linked lysosomal storage disorder caused by deficient activity of iduronate-2-sulfatase in glycosaminoglycan degradation. The enzyme defect results in the accumulation of heparan sulfate and dermatan sulfate in many organs, as well as elevated metabolite levels in urine. The heterogeneity of clinical phenotypes, ranging from mild-to-severe forms, is a result of different mutations in the IDS gene. This disorder is characterized by mental retardation, coarse faces, short stature, hearing loss, hydrocephalus, hepatosplenomegaly, dysostosis multiplex, airway obstruction, and cardiac valve disease.","Inherited metabolic disease; Lysosomal storage disease"
"H00915","Tuberous sclerosis complex","Tuberous sclerosis complex (TSC), also known as Bourneville-Pringle disease, is a rare, slowly progressive genetic disorder characterized by pervasive benign tumors in most organ systems including the brain, skin, kidney, liver, lung, and heart, which is inherited in an autosomal dominant manner. Patients with TSC are frequently diagnosed with comorbid neurological disorders, including epilepsy, intellectual disability, behavioral dysregulation, sleep disorders, and autism spectrum disorders (ASD). TSC most often results from spontaneous genetic mutations in one or two genes, TSC1 and TSC2, which encode hamartin and tuberin, respectively. These gene products form a physical and functional complex to limit activation of the mammalian target rapamycin (mTOR) complex 1. When these genes are deficient, mTOR complex 1 is constitutively up-regulated, leading to uncontrolled cell growth and protein synthesis.","Congenital malformation"
"H01666","Angiosarcoma","Angiosarcomas are rare, generally aggressive, malignant mesenchymal tumours of vascular origin and constitute less than 1% of all sarcomas. Their most frequent site of origin is the head and neck, especially the scalp, of elderly men. Angiosarcomas are likely derived from vascular endothelial cells, possibly resulting from aberrant angiogenesis. Studies have shown relatively increased expression of vascular endothelial growth factor (VEGF) and its receptors (VEGFr1-3) in human angiosarcoma. The most common gene mutation in angiosarcomas is KRAS as well as other RAS mutations. Activation of the RAS pathway is often tumorigenic. Although immortalised murine endothelial cells form benign haemangiomas in vivo, the addition of activated HRAS produces rapidly growing, poorly differentiated angiosarcomas.","Cancer"
"H00586","Epidermolysis bullosa, junctional","Inherited epidermolysis bullosa is a diverse group of disorders characterized by mechanically fragile skin that readily blister. The junctional forms of epidermolysis bullosa are characterized by blister formation within the lamina lucida of the dermal-epidermal basement membrane. Herlitz subtype, the classic form of the disease, shows a severe phenotype that may lead to death during infancy or early childhood owing to infection.","Congenital malformation"
"H01454","Colonic spirochetosis","Colonic spirochetosis (CS) is a disease caused by the Brachyspira genus, Brachyspira aalborgi and Brachyspira pilosicoli. B. pilosicoli induces disease in both humans and animals, whereas B. aalborgi affects only humans and higher primates. CS is a polymicrobial disease characterized by persistent intimate mucosal epithelial cell attachment of spirochetes alone or together with certain enterohepatic Helicobacter species. Symptoms in humans include diarrhea, rectal bleeding, and abdominal cramps.","Infectious disease"
"H01030","Congenital arthrogryposis with anterior horn cell disease","Congenital arthrogryposis with anterior horn cell disease (CAAHD), formerly known as lethal arthrogryposis with anterior horn cell disease (LAAHD), is a condition with fetal akinesia deformation sequence (FADS), multiple contractures and facial anomalies. Motor neuron loss is also present in patients with CAAHD.","Congenital malformation"
"H01202","Cataract","Cataracts can be defined as any opacity of the crystalline lens, often associated with breakdown of the lens microarchitecture, possibly including vacuole formation and disarray of lens cells, which can cause large fluctuations in density resulting in light scattering. In addition, light scattering and opacity will occur if there is a significant amount of high molecular weight protein aggregates. Cataracts can be classified by the age at onset: a congenital or infantile cataract presents within the first year of life; a juvenile cataract presents within the first decade of life; a presenile cataract presents before the age of about 45 years, and senile or age-related cataract after that. Congenital cataracts are a major cause of induced blindness in children, and inherited cataracts are the major cause of congenital cataracts. Inherited congenital cataracts have been associated with mutations in specific genes, including those of crystallins, gap junction proteins, membrane transport and channel proteins, the cytoskeleton, and growth and transcription factors. Inherited congenital cataracts may be inherited as autosomal dominant (most frequent), autosomal recessive, or X-linked traits.","Nervous system disease"
"H02487","Diencephalic-mesencephalic junction dysplasia syndrome","Diencephalic-mesencephalic junction dysplasia syndrome (DMJDS) is a novel autosomal recessive brain malformation. DMJDS is associated with a characteristic butterfly-shaped contour of the midbrain on axial sections on MRI. Patients displayed severe cognitive impairment, post-natal progressive microcephaly, axial hypotonia, spastic quadriparesis and seizures. A few genes that cause DMJDS have been identified.","Congenital malformation"
"H00116","Congenital lactase deficiency","Congenital lactase deficiency is an autosomal recessive disorder caused by enzyme deficiency for metabolizing lactose.","Inherited metabolic disease"
"H00324","Scrub typhus","Scrub typhus, also known as tsutsugamushi disease, is a zoonosis caused by Orientia tsutsugamushi, an obligate intracellular bacterium that is transmitted by the Leptotrombidium species mite. The disease is confined to East Asia and characterized by fever, rash, eschar, pneumonitis, meningitis, and disseminated intravascular coagulation.","Infectious disease"
"H02473","Leukoencephalopathy, brain calcifications, and cysts","Leukoencephalopathy, brain calcifications, and cysts (LCC) is a rare disorder that is radiologically characterized by edematous leukoencephalopathy, cerebral calcifications, and formation of parenchymal cysts. It has been shown that mutations in the gene SNORD118, encoding the box C/D snoRNA U8, cause LCC.","Nervous system disease"
"H00740","Ichthyosis follicularis, alopecia, and photophobia syndrome","Ichthyosis follicularis, alopecia, and photophobia (IFAP) syndrome is a rare X-linked genetic disorder characterized by congenital ichthyosis follicularis and noncicatricial universal alopecia. Photophobia is also present in early childhood. Other features include short stature, seizures, and mental retardation. The causative gene is MBTPS2 which encodes a membrane-embedded zinc metalloprotease involved in endoplasmic reticulum stress response. Recently, it has been reported that mutations in SREBF1, encoding sterol regulatory element binding transcription factor 1, cause autosomal dominant IFAP syndrome.","Congenital malformation"
"H01692","Subependymal giant cell astrocytoma","Subependymal giant cell astrocytoma (SEGA) is the most common central nervous system tumor in patients with tuberous sclerosis complex (TSC). Although these lesions are generally benign and non-infiltrative, they commonly arise in the region of the foramen of Monro, where they can cause obstructive hydrocephalus and sudden death. TSC is an autosomal dominant genetic disorder caused by inactivating mutations in either the TSC1 or TSC2 genes. These mutations lead to constitutive upregulation of the mammalian target of rapamycin (mTOR) pathway, which affects many cellular processes involved in tumor growth. Clinical studies have demonstrated that mTOR inhibitors can induce regression of SEGA in patients with TSC, providing a viable alternative to surgical removal.","Nervous system disease"
"H02017","Sandhoff disease","Sandhoff disease is an autosomal recessive lysosomal storage disorder caused by mutations in HEXB that encodes beta-hexosaminidase subunit beta. Sandhoff disease is characterized by combined deficiency of hexosaminidase A (HexA) and hexosaminidase B (HexB) activities. GM2 ganglioside cannot be hydrolyzed and therefore accumulates primarily in neuronal tissues. This results in progressive neurologic degeneration. The severe form is characterized by an early age of onset and a rapidly progressive clinical course leading to death in early childhood, whereas the juvenile and adult forms start later and generally manifest a less severe course.","Inherited metabolic disease; Lysosomal storage disease"
"H02225","Familial cirrhosis","Familial cirrhosis is a condition that is associated with the presence of liver disease with genetic linkage among multiple family members in a generation or in multiple generations. The well-documented causes of familial cirrhosis are mutations of keratin 8 and 18 gene. They are the cytoskeletal intermediate filament proteins of hepatocytes, and protect the liver from various forms of injury. It has been shown that KRT8 or KRT18 mutations predispose the liver to acute or subacute injury and promote apoptosis and fibrosis.","Digestive system diseases"
"H00572","ESCO2-related disorders","Roberts syndrome is a autosomal recessive disorder featuring severe pre- and postnatal growth retardation, craniofacial anomalies, and tetraphocomelia that is caused by mesomelic shortening. SC phocomelia is milder with less marked limb reduction. Mutations in the ESCO2 gene have been detected in both disorders.","Congenital malformation"
"H00912","Tumor necrosis factor receptor-associated periodic syndrome","The tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is a multisystem auto-inflammatory disorder that is inherited in an autosomal dominant manner. It is characterized by recurrent febrile attacks and localized inflammation in the absence of autoantibodies. Recurrent fever, abdominal pain, myalgia, and arthralgia are the most common manifestations of TRAPS.","Immune system disease"
"H00778","Tarsal-carpal coalition syndrome","Tarsal-carpal coalition syndrome is a condition characterized by fusion of the carpals, tarsals, and phalanges in addition to shortened first metacarpals, brachydactyly, and humeroradial fusion. The fusion of the proximal interphalangeal joints starts at the fifth digit and proceeds to other digits. Humeroradial fusion can also be seen. It is inherited in an autosomal dominant pattern.","Congenital malformation"
"H01498","Multiple joint dislocations, short stature, craniofacial dysmorphism, and congenital heart defects","Multiple joint dislocations, short stature, craniofacial dysmorphism, and congenital heart defects (JDSSDHD), also termed Larsen-like syndrome, is an autosomal recessive disease that is caused by the mutations in the B3GAT3. B3GAT3 encodes key enzyme involving in glycosaminoglycan biosynthses. The mutation results in decreased levels of dermatan sulfate, chondroitin sulfate, and heparan sulfate proteoglycans. The affected individuals showed dysmorphic faces, bilateral dislocations of the elbows, hips, and knees, and short stature, as well as cardiovascular defects.","Congenital disorder of metabolism"
"H01008","C syndrome","The C syndrome/ Opitz trigonocephaly syndrome is characterized by trigonocephaly and associated anomalies, such as unusual facies, psychomotor retardation, redundant skin, joint and limb abnormalities, and visceral anomalies. The C syndrome is caused by mutations in CD96, a member of the immunoglobulin superfamily.","Congenital malformation"
"H01834","Marshall-Smith syndrome","Marshall-Smith syndrome (MSS) is a distinct malformation syndrome characterized by accelerated skeletal maturation, relative failure to thrive, respiratory difficulties, mental retardation, and unusual facies, including prominent forehead, shallow orbits, blue sclerae, depressed nasal bridge, and micrognathia. The majority of reported cases died in infancy or early childhood commonly from respiratory compromise. A study demonstrates that NFIX haploinsufficiency is responsible for MSS.","Congenital malformation"
"H02222","Methylmalonic acidemia and hyperhomocysteinemia, cblX type","Methylmalonic acidemia and hyperhomocysteinemia (MAHC) cblX type is X-linked form of combined methylmalonic acidemia and hyperhomocysteinemia. The clinical symptoms are similar to MAHC cblC type, that is caused by mutations in MMACHC gene. They can feature neurologic, renal, cardiac, hematologic, and ophthalmologic manifestations. MAHC cblX type is caused by mutations in transcriptional coregulator HCFC1. Functional analysis implicated HCFC1 in transcriptional regulation of MMACHC.","Congenital disorder of metabolism"
"H00575","Renal tubular dysgenesis","Autosomal recessive renal tubular dysgenesis (RTD) is a rare lethal disorder characterized by the absence or incomplete differentiation of proximal tubules. Patients present persistent fetal anuria leading to oligohydramnios sequence. Homozygous or compound heterozygous mutations in the genes encoding renin, angiotensinogen, angiotensin converting enzyme or angiotensin II receptor type 1 may cause RTD. These genes are renin-angiotensin system components which regulate renal growth during embryogenesis.","Congenital malformation"
"H00747","Thyrotoxic hypokalemic periodic paralysis","Thyrotoxic hypokalemic periodic paralysis (TPP) is characterized by thyrotoxicosis in combination with typical episodes of hypokalemic periodic paralysis (HypoPP). People of Asian descent are most often affected, but all ethnicities can present with TPP. Hypokalemia is typical during paralysis, but is not always detected; administration of potassium during the attacks should be offered cautiously, preferably orally, to prevent rebound hyperkalemia. Mutations have been identified in TPP patients in an inwardly rectifying potassium channel, , that is expressed in muscle and transcriptionally regulated by thyroid hormone. Mutations in Kir2.6, which occur in up to 33% of patients, reinforces the hypothesis of genetic heterogeneity in patients with TPP.","Nervous system disease; Musculoskeletal disease; Congenital disorder of metabolism"
"H01695","Erythema multiforme","Erythema multiforme (EM) is an immune-mediated, mucocutaneous condition characterized by 'target' lesions. Classically, EM has been separated into 2 subgroups, EM minor and EM major. In EM minor, lesions often present as papules, which might enlarge and eventually form the typical target lesion with erythema surrounding an area of central clearing. The rash in EM minor preferentially affects the limbs, specifically the extensor surfaces, however, it can also be seen throughout the body, excluding mucous membranes. EM major has mucous membrane involvement. The oral mucosa is most commonly affected, initially with edema that progresses to superficial erosions. Other surfaces that might be involved include the anogenital, ocular, and nasal mucosa. Although previously thought to be on a similar continuum of EM, and histologically appearing the same, Stevens-Johnson syndrome (SJS) is increasingly being considered a separate disease process. It is currently believed that EM is a result of an immune reaction to an inciting infectious or pharmacologic antigen. The most common infectious organisms in EM are herpes simplex virus types 1 and 2, as well as Mycoplasma pneumonia. The first line of treatment for EM is removal of the inciting factor when possible. Systemic steroids have been suggested as adjuvant therapy based on their immunosuppressant effects. To date, their use has been limited to EM major, as EM minor is self-limited.","Skin and connective tissue disease"
"H02010","Galactose epimerase deficiency","Galactose epimerase deficiency is the least understood form of galactosemia. Originally, galactose epimerase deficiency was identified as a biochemical oddity that impacted only red and white blood cells in apparently healthy individuals. This condition was termed 'peripheral type' because it impacted only cells in peripheral circulation. Subsequently, rare patients were identified who were severely symptomatic and demonstrated epimerase deficiency in various cell types, and it was termed 'generalized type'.","Inherited metabolic disease"
"H00323","Spotted fever","Tick-borne rickettsioses are caused by gram-negative obligate intracellular bacteria belonging to the spotted fever group (SFG) of the genus Rickettsia within the family Rickettsiaceae in the order Rickettsiales. The diseases present with high fever, an inoculation eschar, and a maculopapular rash.","Infectious disease"
"H02474","Blepharocheilodontic syndrome","Blepharocheilodontic syndrome (BCDS) is a rare autosomal dominant disorder characterized by eyelid malformations, cleft lip/palate, and ectodermal dysplasia. It has been reported that BCDS is caused by mutations in CDH1 and CTNND1. They are members of the cadherin-catenin complex.","Congenital malformation"
"H00111","Typhoid fever","Typhoid fever, or typhoid, caused by Salmonella enterica serovar Typhi is a systemic febrile disease and endemic disease in many areas of the world, mainly in developing countries. Typhoid is transmitted through ingestion of contaminated water or food and characterized by a variable incubation period ranging from three days to one month.","Infectious disease"
"H01205","Coumarin resistance","Warfarin is widely prescribed anticoagulant for the prevention of thromboembolic diseases. However, its use is made difficult by the wide interindividual variation in dose required to achieve a therapeutic effect, the narrow therapeutic range, and the risk of serious bleeding. Warfarin dose requirement is influenced by factors such as intake of vitamin K, ethnicity, age, gender, and genetic factors. Warfarin acts through interference with the recycling of vitamin K in the liver. It has been reported that mutations in VKORC1, CYP2C9, and GGCX cause warfarin resistance.","Inherited metabolic disease"
"H02480","Fontaine progeroid syndrome","Fontaine progeroid syndrome (FPS) is a rare genetic disorder characterized by early aging, bone dysplasia, characteristic face, and early demise. Mutations in SLC25A24, that encodes for calcium-binding mitochondrial carrier protein, cause FPS. Formerly, FPS was separated into two syndromes, Gorlin-Chaudhry-Moss syndrome and Fontaine-Farriaux syndrome. Because they share similar clinical manifestations and have common genetic basis, it has been proposed to be integrated into a single disorder.","Congenital malformation"
"H01037","Vesicoureteral reflux","Vesicoureteral reflux (VUR) is the abnormal retrograde urinary flow from the bladder to the kidney that affects approximately 1% of the general population. It is associated with an increased risk of recurrent urinary tract infection, pyelonephritis, and renal scarring.","Urinary system disease"
"H00581","Alport syndrome","Alport syndrome is a hereditary hematuric nephropathy with frequent hearing loss and ocular anomalies. Defects of basement membranes arise from mutations in alpha 3, alpha 4, and alpha 5 type IV collagen chains. The mode of inheritance is either X-linked or autosomal recessive, although autosomal dominant form has been observed in a few families. Male patients with X-linked Alport syndrome suffer from severe renal symptoms that progress to end-stage renal disease associated with deafness which starts during the first decade of life, and ocular lesions including anterior lenticonus. Autosomal recessive Alport syndrome is usually severe, showing progressive nephritis and hearing impairment.","Congenital malformation"
"H01453","Obsessive-Compulsive and Related Disorder","Obsessive-Compulsive and Related Disorder (OCRD) is a group of disorders that is characterized by having preoccupations (obsessions) and/or repetitive behaviors (compulsions). Previously, Obsessive-compulsive disorder (OCD) was grouped with the anxiety disorders. However, the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) moved OCD into a new category, because much of the evidence suggests OCD and OC-spectrum disorders are distinct from other anxiety disorders. Although OCD and anxiety disorders often share core clinical feature, significant differences also exist in effective first-line pharmacological interventions. Patients with anxiety disorders respond to a wide range of pharmacological interventions. In contrast, patients with OCD do not respond to nonserotonergic agents. OCRD includes OCD, Trichotillomania, Hoarding disorder, Excoriation disorder, and Body dysmorphic disorder.","Mental and behavioural disorder"
"H01661","Xanthoma","Xanthomas are benign and usually yellow plaques, papules, or nodules that develop in the cutis and subcutaneous tissue. They evolve as clusters of foam cells and favor the neck, upper trunk, flexural folds and periorbital region. The foam cells are formed from macrophages as a consequence of gradual intracellular accumulation of lipids taken up by specific receptors or by the mechanism of phagocytosis. They are seen in several lipidoses and are usually indicative of a derangement in lipoprotein metabolism, in particular familial hypercholesterolemia. Prevention of xanthomas goes hand in hand with the management of the underlying disorders of lipid metabolism. Normolipemic xanthomatosis may be seen in several rare conditions.","Congenital disorder of metabolism"
"H02044","Cutaneous and mucosal venous malformation","The multiple cutaneous and mucosal venous malformations (VMCM) is characterized by the presence of small, multifocal bluish cutaneous and mucosal venous malformations. TEK (TIE2) is the only gene in which pathogenic variants are known to cause VMCM. TIE2 is vascular endothelial cell specific receptor tyrosine kinase, that plays a crucial role in angiogenesis and cardiovascular development.","Congenital malformation"
"H00713","Beckwith-Wiedemann syndrome","Beckwith-Wiedemann syndrome (BWS) is an imprinting disorder characterized by overgrowth, tumor predisposition, and congenital malformations. It is associated with genetic or epigenetic abnormalities in a cluster of imprinted genes found within a genomic region of approximately one megabase on chromosome 11p15. The imprinted region 11p15 is separated into two domains, with each domain regulated by a functionally independent imprinting control regions (ICR). The centromeric ICR2 regulates the expression of CDKN1C, KCNQ1, and further genes. The majority of cases of BWS show hypomethylation in the ICR2 or mutations in the ICR2-regulated CDKN1C gene. In intron 10 of the KCNQ1 locus, the untranslated KCNQ1OT1 RNA is encoded. KCNQ10T1 is expressed by the paternal allele and probably represses realization of the CDKN1C gene. In the telomeric ICR1, hypermethylation of the H19 promoter and loss of imprinting of IGF2 have been reported in a small fraction of patients with BWS. A few BWS cases could be related to NSD1 deletions or mutations.","Congenital malformation"
"H00521","Cleidocranial dysplasia","Cleidocranial dysplasia is an autosomal dominant skeletal dysplasia characterized by hypoplastic clavicles, delayed closure of the cranial sutures, and dental abnormalities resulted from defective intramembranous ossification. Mutations in RUNX2, which is involved in osteoblast differentiation, is the cause of the disease.","Congenital malformation"
"H02276","Kufs disease","Kufs disease, an adult-onset neuronal ceroid lipofuscinosis (NCL), differs from most other forms of NCL because the retina is not involved, and vision is preserved. The clinical presentation has been divided into two types. Type A presents with progressive myoclonus epilepsy, whereas type B presents with dementia and a variety of motor disturbances. It has been reported that mutations in CLN6 cause recessive type A Kufs disease. Mutations in DNAJC5 have been found in some cases of dominant Kufs disease, also presenting with progressive myoclonus epilepsy. Mutations in CTSF were recently identified in recessive type B Kufs disease.","Congenital disorder of metabolism"
"H00979","Caudal regression syndrome and Sirenomelia","Caudal dysgenesis and sirenomelia are rare malformations that represent a spectrum of caudal anomalies. Clinical findings include varying degrees of agenesis of the vertebral column (usually sacral or lumbosacral spine), as well as anorectal and genitourinary anomalies. The most severe end of this spectrum is known as sirenomelia that is characterized by fused lower limbs. These are caused by developmental field defects of blastogenesis involving the caudal mesoderm and usually sporadic.","Congenital malformation"
"H01097","Spastic quadriplegic cerebral palsy","Spastic quadriplegic cerebral palsy (CPSQ) is a heterogeneous group of neurodevelopmental brain disorders resulting in motor and posture impairments often associated with cognitive, sensorial, and behavioural disturbances. It is thought that a half of idiopathic cerebral palsy cases are caused by genetic factors, such as mutations in GAD1, KANK1, and ADD3.","Nervous system disease"
"H00145","Aspartylglucosaminuria","Aspartylglucosaminuria (AGU) is an autosomal recessive lysosomal storage disorder caused by deficiency of aspartylglucosaminidase, which is a key enzyme in the catabolism of N-linked oligosaccharides of glycoproteins. The enzymatic defect results in inappropriate accumulation of aspartylglucosamines in various organ systems as well as elevated metabolite levels in urine. The main symptoms of aspartylglucosaminuria are progressive mental retardation, coarce faces, behavioral, and hepatosplenomegaly.","Inherited metabolic disease; Lysosomal storage disease"
"H02420","Head and neck cancer","Head and neck cancers are a heterogeneous collection of malignancies of the upper aerodigestive tract, salivary glands and thyroid. The most common type of cancer in the head and neck is squamous cell carcinoma. It mainly originates from the mucosal space, which extends from the skull base to the proximal esophagus. The head and neck region is subdivided in the oral cavity, pharynx and larynx. The pharyngeal space contains the nasopharynx, oropharynx and hypopharynx and includes the tonsils, the floor of the mouth and the soft palate. Although head and neck squamous cell carcinoma (HNSCC) is traditionally associated with smoking and alcohol drinking, a growing proportion of head and neck tumors, mainly of the oropharynx, are associated with human papilloma virus (HPV).","Cancer"
"H00377","Rabies","Rabies is a typical zoonotic disease caused by rabies virus that belong to the genus Lyssavirus, within the family Rhabdoviridae and the order Mononegavirales of -ssRNA viruses. Dogs are the major vectors. Rabies affects the central nervous system and causes fatal encephalomyelitis.","Infectious disease"
"H01063","Human metapneumovirus infection","Human metapneumovirus (hMPV) is an emerging human respiratory pathogen first reported in 2001. hMPV is widely distributed that nearly all individuals have been exposed to the virus by age of 5 years. It causes mild to severe cough, bronchiolitis, and pneumonia and these symptoms cannot be distinguished from those caused by the respiratory syncytial virus, influenza, and parainfluenza viruses.","Infectious disease"
"H01251","Focal cortical dysplasia of Taylor","Focal cortical dysplasia of Taylor (FCDT) is a subtype of cortical displasias. FCDT is characterized by epilepsy associated malformations that are often composed of balloon cells and dysplastic neurons. It has been found that inherited mutations in the TSC1 gene can cause this disorder.","Congenital malformation"
"H00383","Arthropod-borne viral fever","Arthropod-borne viral fevers are infectious diseases caused by arboviruses (arthropod-borne viruses) and transmitted by mosquitoes, other insects, mites and ticks. Arboviruses are zoonotic viruses and actually consist of taxonomically different viruses, including flavivirus, alphavirus and bunyavirus.","Infectious disease"
"H01635","Hyperlipidemia","Dyslipidemia is a condition characterized by either an increase or decrease in concentration of lipids in the blood. Hyperlipidemia, which refers to an increase in cholesterol, triglyceride (TG), or both, is the most common form of dyslipidemia. Hyperlipidemias can be classified as familial (also called primary) caused by an inherited gene mutation, or acquired (also called secondary) when resulting from underlying disorders that lead to alterations in plasma lipid and lipoprotein metabolism. The causes of acquired hyperlipidemia include dietary, alcohol intake, oral contraceptives, diabetes mellitus, and pharmacological agents (e.g., retinoic acid derivatives, steroids, and beta-blockers). Familial hyperlipidemias are classified according to the Fredrickson classification (hyperlipoproteinemia types I to V) which is based on lipoprotein analyses by electrophoresis or ultracentrifugation. It was later adopted by the World Health Organization (WHO). Hyperlipidemias are also classified according to which types of lipids are elevated. Hypercholesterolemia, hypertriglyceridemia, and combined hyperlipidemia refer to elevations involving the major cholesterol-rich lipoproteins (LDL), triglyceride-rich lipoproteins (VLDL), and both, respectively.","Metabolic disease"
"H01407","Capnocytophaga ochracea infection","Capnocytophaga ochracea is a Gram-negative bacterium, capnophilic (CO2-requiring) organism, originally isolated from a human oral cavity. C. ochracea is a normal inhabitant of the human mouth and other non-oral sites and associated with juvenile and adult periodontitis and may cause severe infections in immunocompromised as well as in immunocompetent patients.","Infectious disease"
"H02282","Spastic tetraplegia, thin corpus callosum, and progressive microcephaly","Spastic tetraplegia, thin corpus callosum, and progressive microcephaly (SPATCCM) is an autosomal recessive neurodevelopmental disorder of childhood. Mutations in SLC1A4, encoding the brain serine transporter, are associated with this syndrome. L-serine plays an essential role in neuronal development and function.","Congenital malformation"
"H00348","Lymphogranuloma venereum","Chlamydia trachomatis is a gram-negative, obligate intracellular bacterium that causes the most common sexually transmissible diseases in the world. Serovars L1, L2, L2a and L3 of C. trachomatis are the agents of lymphogranuloma venereum, a disease found in isolated groups of men who have sex with men (MSM) across Western Europe, North America, and Australia.","Infectious disease"
"H01894","Multiple mitochondrial dysfunctions syndrome","Multiple mitochondrial dysfunctions syndrome (MMDS) is a severe autosomal recessive disease with onset in early infancy. Pathogenic variations in genes encoding several components of the Fe-S cluster biogenesis machinery are already implicated in causing five types of MMDS. All MMDS share variable neurodevelopmental delay, regression, seizures, lactic acidosis and leukodystrophy resulting in early death of affected individuals.","Inherited metabolic disease; Mitochondrial disease"
"H00946","Arts syndrome","Arts syndrome is an X-linked disorder characterized by mental retardation, early-onset hypotonia, delayed motor development, ataxia, congenital sensorineural hearing impairment, and optic atrophy. Patients with Arts syndrome also have an impaired immune system due to impaired hematopoietic differentiation. The causative gene is PRPS1 on the X chromosome that is essential for de novo purine and pyrimidine synthesis.","Congenital malformation"
"H02249","Primrose syndrome","Primrose syndrome (PRIMS) is a rare genetic disorder, characterized by dysmorphic facial features, macrocephaly, and intellectual disability, as well as large body size, height and weight, and calcified pinnae. Recently, mutations in ZBTB20, coding for a zing finger protein, have been identified in PRIMS patients.","Congenital malformation"
"H01438","Neurofibromatosis type 2","Neurofibromatosis 2 (NF2) is a rare autosomal dominant multiple neoplasia syndrome that is caused by inactivating mutations of the NF2 tumour suppressor gene. The course of the disease is usually progressive, though variable, causing significant morbidity associated with deafness, blindness, brain stem compression, gait instability, and paralysis. Onset typically occurs while a patient is in their 20s. Vestibular schwannomas, usually bilateral, occur in more than 90% of adult patients and intracranial meningiomas occur in about 50% of patients.","Congenital malformation"
"H01860","Abnormal pituitary gonadotropin secretion","There are two pituitary gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Their general biological roles are the stimulation of testicular and ovarian functions via the regulation of gametogenesis and steroid hormone synthesis in the gonads. Synthesis and release of FSH is triggered by the arrival of gonadotropin-releasing hormone (GnRH) from the hypothalamus. LH is synthesized similarly within the pituitary gland, requiring the same stimulus as FSH, the GnRH from the hypothalamus. Both hypothalamic abnormalities and intrinsic pituitary abnormalities can cause an abnormal FSH/LH response to GnRH. Hypersecretion of gonadotropins are often associated with pituitary adenomas [DS:H01102] and central precocious puberty [DS:H00937]. Hyposecretion of gonadotropins [DS:H00255 H01700] in premenopausal women leads to absent menstrual cycles, infertility, vaginal dryness, and loss of some female characteristics. In men, this deficiency leads to impotence, atrophy of the testes, decreased sperm production, infertility, and loss of some male characteristics.","Endocrine disease"
"H01400","Secondary hyperammonemia","Hyperammonemia is a metabolic condition characterized by elevated levels of ammonia in the blood, and may result in irreversible brain damage if not treated early and thoroughly. Hyperammonemia can be classified into primary or secondary hyperammonemias depending on the underlying pathophysiology. Detoxification of ammonia is mainly accomplished by the urea cycle in periportal hepatocytes. The function of the urea cycle may be affected in a secondary way in a number of different situations. For example, intermediary metabolites that accumulate due to enzymatic defects in other pathways, may inhibit the urea cycle. The most relevant group of disorders in this respect is that of organic acidemias. The urea cycle function may be impaired by substrate deficiencies assumed cause in various disorders including lysinuric protein intolerance, pyrroline-5-carboxylate synthetase deficiency, and fatty acid oxidation defects. In addition to the urea cycle, mammals require the function of glutamine synthetase to completely detoxify ammonia.","Inherited metabolic disease"
"H02285","Methylmalonate semialdehyde dehydrogenase deficiency","Methylmalonate semialdehyde dehydrogenase (MMSDH) deficiency is a rare autosomal recessive disorder with varied metabolite abnormalities, including accumulation of 3-hydroxyisobutyric, 3-hydroxypropionic, and methylmalonic acids, as well as beta-alanine. Reported clinical presentations vary from a mild or uneventful clinical course. Severe developmental delay may be present. Dysmorphic facial features and congenital brain dysgenesis with intracerebral calcifications have also been described. Mutations in the ALDH6A1 gene coding for MMSDH are associated with this disease.","Congenital disorder of metabolism"
"H01632","Angina pectoris","Angina pectoris is defined as cardiac-induced pain arising from a lack of myocardial oxygen. 'Angina' is used to describe clinical symptoms such as discomfort in the chest, jaw, shoulder, back, or arms that are induced by physical exertion or emotional stress and subside with rest or treatment with nitroglycerin. Angina is clinically classified into stable angina (SA) and unstable angina (UA). SA is a chronic medical condition while UA is an acute coronary syndrome. Among the causes of angina pectoris, the most common is coronary artery disease (CAD). At the cellular level, angina pectoris is a result of increased myocardial oxygen demand or decreased myocardial oxygen supply.","Cardiovascular disease"
"H01256","Foveal hypoplasia","Foveal hypoplasia (FVH) is characterized by absence or abnormal foveomacular reflex, unclear definition of the foveomacular area, and presence of capillaries running abnormally close to the macula. It can be isolated or associated with presenile cataract. The mutations in the PAX6 gene have been described in foveal hypoplasia. Recently, it has been reported that recessive mutations in SLC38A8 cause foveal hypoplasia.","Nervous system disease"
"H00384","Yellow fever","Yellow fever is an infectious disease caused by Yellow fever virus (YFV), a flavivirus in the Flaviviridae family of +ssRNA viruses, and transmitted by Aedes mosquitoes. YFV was was first isolated in 1927 in West Africa.","Infectious disease"
"H01858","Persistent cloaca","Persistent cloaca is an uncommon congenital anomaly in which there is a single perineal opening for the urinary, gastrointestinal, and reproductive tracts. It is the most severe form of anorectal malformation encountered in girls. The incidence is approximately 1 in 50,000 live births. Persistent cloaca results from abnormal development of the cloacal membrane before 50 days post fertilization. In addition to a single perineal opening, secondary urogenital or gastrointestinal anomalies are often associated with persistent cloaca. Moreover, anomalies of other organ systems such as cardiac or skeletal malformations are known to coexist. The common channel of persistent cloaca varies from 1 cm to 10 cm. Those cases with a common channel longer than 3 cm are predicted with the higher incidence of complications. For patients with a common channel greater than 3 cm, a laparotomy is usually required.","Congenital malformation"
"H01064","Simkania negevensis infection","Simkania negevensis is a recently found Chlamydia-like organism. It is associated with respiratory diseases such as pneumonia in adults and bronchiolitis in infants.","Infectious disease"
"H02427","Soft tissue sarcomas","Soft-tissue sarcomas (STS) are a rare and heterogeneous group of tumors with mesenchymal origin, including muscle, endothelium, cartilage. Several common STSs have recognized translocations, which represent clinical targets. In addition to translocations, other genomic changes and epigenetic mechanisms have been shown to be involved in the histogenesis of STS as well as other cancers.","Cancer"
"H00370","Progressive multifocal leukoencephalopathy","Progressive multifocal leukoencephalopathy (PML) is a fatal neurological disorder characterized by destruction of oligodendrocytes by the JC polyomavirus that occurs in immunosuppressed individuals such as patients with AIDS. Patients with PML show white matter lesions on head computed tomography scan or magnetic resonance imaging.","Infectious disease"
"H01090","Ascariasis","Ascariasis is a commonly documented parasitic infection in sub-Saharan Africa, the Americas, China, and east Asia. Morbidity and mortality increase with worm burden and those who harbor light infections tend to be asymptomatic.","Infectious disease"
"H00142","Sialidosis","Sialidosis is an autosomal recessive lysosomal storage disorder caused by deficient activity of sialidase (neuraminidase). The enzymatic defect results in the accumulation of sialidated glycopeptides and oligosaccharides in many organs. The disease is classified into two types: type 1 for the mild form with late-onset and type 2 for the severe form with infantile onset.","Inherited metabolic disease; Lysosomal storage disease; Nervous system disease"
"H00526","Camptodactyly-arthropathy-coxa vara-pericarditis syndrome","The camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP) is an autosomal recessive disorder caused by mutations in the Proteoglycan 4 (PRG4), a chondroitin sulfate proteoglycan that acts as a lubricant for the cartilage surface. Affected individuals present with arthropathy associated with camptodactyly. Some patients have pericarditis with effusions.","Congenital malformation"
"H02271","Cerebellofaciodental syndrome","Cerebellofaciodental syndrome (CFDS) is an autosomal recessive disorder characterized by cerebellar hypoplasia and intellectual disability, as well as facial dysmorphic features, short stature, microcephaly, and dental anomalies. Biallelic missense alterations of BRF1 have been revealed in CFDS families. It is suggested that BRF1 mutations alter RNA polymerase III-dependent transcription and cause neurodevelopmental anomalies.","Congenital malformation"
"H02043","Capillary malformation-arteriovenous malformation","Capillary malformation-arteriovenous malformation (CMAVM) is an autosomal dominant disorder associated with heterozygous mutations in RASA1. CM-AVM is with multiple CMs on the skin, sometimes in association with AVMs or fistulas (AVF). CMs in this syndrome usually present at birth, and are progressive, round to oval, pink or red, and with a pale halo.","Congenital malformation"
"H00714","Vohwinkel syndrome","Vohwinkel syndrome is a diffuse palmoplantar keratoderma associated with sensorineural deafness. One of the identifiable characteristics of the disorder is the constriction bands of the digits, leading to autoamputation (pseudoainhum). Vohwinkel syndrome is caused by GJB2 mutations, and its variant that is linked to loricrin also has a feature of ichthyosis.","Congenital malformation"
"H01867","Congenital anomalies of kidney and urinary tract","Congenital anomalies of the kidney and urinary tract (CAKUT) include a wide range of structural malformations resulting from defects in the morphogenesis of the kidney and of the urinary tract. CAKUT represent a broad spectrum of abnormalities, from transient hydronephrosis to severe bilateral renal agenesis. The most severe cases of CAKUT (bilateral aplasia, hypoplasia, dysplasia, obstructive uropathy, and reflux nephropathy) are the leading cause of pediatric end-stage renal disease (ESRD) in children. Both genetic abnormalities and the fetal environment contribute to CAKUT.","Congenital malformation"
"H00189","Ornithinaemia","Ornithinemia due to deficiency of ornithine ketoacid aminotransferase induces hyperornithinemia and gyrate atrophy.","Inherited metabolic disease; Eye disease"
"H01269","Congenital hyperthyroidism","Congenital hyperthyroidism is a rare clinical condition, and in most cases, it is a transient disorder caused by maternal Graves disease associated with the transplacental passage of maternal thyroid-stimulating antibodies. Germline mutations of thyrotropin receptor (TSHR) gene determining a constitutive activation of the receptor were identified as a molecular cause of congenital nonautoimmune hyperthyroidism. TSHR gene mutations also causes the familial gestational hyperthyroidism, that is characterized by thyrotoxicosis and hyperemesis gravidarum.","Endocrine disease"
"H02088","Primary intraosseous vascular malformation","Primary intraosseous vascular malformation (VMPI), previously called intraosseous hemangioma, is a very rare malformation that is usually seen in the vertebral column and in the skull. It is almost exclusively described in sporadic cases. It has recently been reported that loss-of-function mutations in ELMO2 is causative for VMPI in different families.","Cardiovascular disease"
"H00519","Spondyloepiphyseal dysplasia congenita","Spondyloepiphyseal dysplasia congenita (SEDC) is an autosomal dominant chondrodysplasia characterized by disproportionate short stature (short trunk), abnormal epiphyses, and flattened vertebral bodies. Individuals with SED, Stanescu type (SEDS) are not short, although spondylar and epiphyseal abnormalities are radiologically quite conspicuous. Mutations in COL2A1 that encodes the alpha-1 chain of type II collagen, cause these diseases.","Congenital malformation"
"H01893","Lateral meningocele syndrome","Lateral meningocele syndrome (LMS), also known as Lehman syndrome, is a rare hereditary connective tissue disorder characterized by pan-spinal meningoceles, specific facial dysmorphism, skeletal and soft tissue abnormalities, and hypotonia and/or muscle weakness. The characteristic lateral meningoceles represent the severe end of the dural ectasia spectrum and are typically most severe in the lower spine. Facial features of LMS include hypertelorism and telecanthus, high arched eyebrows, ptosis, midfacial hypoplasia, micrognathia, high and narrow palate, low-set ears, and a hypotonic appearance. Hyperextensibility, hernias and scoliosis reflect a connective tissue abnormality, and aortic dilation, a high-pitched nasal voice, wormian bones, and osteolysis may be present. NOTCH3 gain of function mediated via loss of the PEST degradation domain is associated with LMS.","Congenital malformation"
"H00941","Factor XII deficiency","Factor XII (FXII) deficiency is a rare autosomal recessive disorder. Although FXII deficiency is not associated with a clinical bleeding tendency, FXII is an important protease that plays a major role in the initiation of the intrinsic pathway of blood coagulation. Venous or arterial thrombosis, recurrent miscarriages, and placental abruption were reported in cases with FXII deficiency.","Hematologic disease"
"H02418","Non-Hodgkin lymphoma","Non-Hodgkin lymphoma (NHL) is one of the most common hematologic malignancies worldwide. NHL includes malignant tumors of the lymphoid tissues variously resulting from the clonal growth of B cells, T cells and natural killer cells. NHL can be broadly classified based on the type of lymphocyte involved: B lymphocyte (B cell) or T lymphocyte (T cell) and is further classified by other factors, including whether it is aggressive or indolent. Aggressive NHL is fast-growing disease. It mainly includes mantle cell lymphoma, diffuse large B-cell lymphoma, Burkitt's lymphoma, lymphoblastic lymphoma and peripheral T-cell lymphoma. On the other hand, indolent NHL is slow-growing disease. It mainly includes follicular lymphoma, cutaneous T-cell lymphoma, lymphoplasmacytic lymphoma and MALT lymphoma.","Cancer"
"H01260","Glomerulopathy with fibronectin deposits","Glomerulopathy with fibronectin deposits (GFND) is a hereditary kidney disease with proteinuria, microscopic hematuria, and hypertension that lead to end-stage renal failure in the second to sixth decade of life. It has been reported that mutations in FN1, which encodes fibronectin, are the cause of GFND.","Kidney disease"
"H00180","Holocarboxylase synthetase deficiency","Holocarboxylase synthetase (HLCS) deficiency is an autosomal recessive disorder of biotin metabolism that results from holocarboxylase synthetase activity disruption. HLCS deficiency is also called multiple carboxylase deficiency, because deficient HLCS activity results in reduced activity of multiple carboxylases. In humans, four carboxylases are known to be biotinylated by HLCS. They are pyruvate carboxylase, propionyl-CoA carboxylase, methylcrotonyl-CoA carboxylase, and acetyl-CoA carboxylase. Symptoms of HLCS deficiency include metabolic acidosis, a characteristic organic aciduria, lethargy, hypotonia, convulsions, and dermatitis.","Inherited metabolic disease"
"H01052","Molluscum contagiosum","Molluscum contagiosum is a highly contagious poxvirus infection of the mucous membranes and skin that usually affects school-aged children. The infection is transmitted by close physical contact, fomites, and autoinoculation. It is a benign and self-limiting disease, with the majority of lesions spontaneously resolve within 2-4 years without active treatment.","Infectious disease"
"H01436","Guillain-Barre syndrome","Guillain-Barre syndrome (GBS) is an acute polyneuropathy characterized by progressive motor weakness of limbs with areflexia. This disease is usually triggered by an infection, which provokes immune-mediated nerve dysfunction. GBS can be subdivided into the classic acute demyelinating type, acute motor axonal neuropathy (AMAN), and acute motor and sensory axonal neuropathy (AMSAN). Classic acute demyelinating type is designated acute inflammatory demyelinating polyneuropathy (AIDP), representing the great majority of cases in Europe and North America. A mutation in the PMP22 gene was identified in a family with AIDP. AMAN is the most prevalent form in China. The incidence of AMSAN is very low. The axonal forms of GBS are caused by certain autoimmune mechanisms, due to a molecular mimicry between antecedent bacterial infection (particularly Campylobacter jejuni) and human peripheral nerve gangliosides.","Nervous system disease"
"H01604","Polymyositis and dermatomyositis","Polymyositis (PM) and dermatomyositis (DM) are the two major forms of inflammatory muscle diseases. PM and DM, along with sporadic inclusion-body myositis (sIBM), belong to the heterogeneous group of the idiopathic inflammatory myopathies (IIMs), which are characterized by weakness and chronic inflammation of skeletal muscle. PM and DM differ in their clinical features, histopathology, response to treatment, and prognosis. Although their clinical pictures differ, they both present with symmetrical, proximal muscle weakness. PM is a term that was used traditionally to denote all IIMs that were not DM or sIBM, but it is now a controversial entity with questionable specificity. Traditionally, PM is described as presenting with weakness of the proximal muscles that evolves over weeks to months and affects adults, but rarely children. DM typically includes subacute progressive proximal muscle weakness and a skin rash. The disease mechanisms of PM and DM that cause muscle damage and dysfunction are not fully understood. However, because of the association with other autoimmune diseases, the presence of autoantibodies, and response to immunosuppressive medication, they are believed to be autoimmune in origin. Recent studies have highlighted the importance of the innate immune system and non-immune mechanisms and described novel adaptive immune-based pathways in the pathogenesis of PM and DM. Treatment of inflammatory myopathies is generally empirical. Corticosteroids still remain the agents of choice for the initial treatment, but their use is limited by the high frequency of side effects. In addition, as a substantial number of patients do not respond to glucocorticoids alone, additional agents such as immunosuppressants, immunomodulators, and more recently, biologics are commonly used in clinical practice.","Musculoskeletal disease"
"H02081","Marshall syndrome","Marshall syndrome is a rare autosomal dominant skeletal dysplasia caused by mutations in COL11A1, which encodes collagen type XI alpha-1 chain. It is characterized by midfacial hypoplasia, high myopia, and sensorineural-hearing deficit.","Congenital malformation"
"H02247","Ehlers-Danlos syndrome myopathic type","Ehlers-Danlos syndrome myopathic type (EDSMYP), also known as Bethlem myopathy 2 (BTHLM2), shows clinical features of both a myopathy as well as of a disorder of connective tissue. Although symptoms are similar to that of the collagen VI-related myopathy, patients don't have mutations in collagen VI. It has been reported that mutations in in collagen XII (COL12A1) cause this disease.","Congenital malformation"
"H00510","Feingold syndrome","Feingold syndrome (FGLDS) is characterized by limb malformations, microcephaly, esophageal/duodenal atresias, and learning disability. Feingold syndrome is caused by mutations in MYCN and inherited as an autosomal dominant trait. Recently, individuals sharing the skeletal abnormalities of FGLDS but lacking mutations in MYCN, were found to harbour deletions of the MIR17HG gene. These individuals share many of the characteristics of FGLDS except for gastrointestinal atresia. The condition was termed Feingold syndrome type 2 (FGLDS2).","Congenital malformation"
"H00722","Epidermolytic palmoplantar keratoderma","Epidermolytic palmoplantar keratoderma (EPPK) is an autosomal dominant dermatosis that present within the first year of life. Patients have diffuse thickening of the skin on the palms and soles with yellow discoloration and erythematous margins. Mutations are identified in KRT9. Mild form of EPPK is linked to KRT1.","Congenital malformation"
"H02075","Enhanced S-cone syndrome","Enhanced S-cone syndrome (ESCS) is a rare autosomal recessive retinal dystrophy that results in an increased function of the short wavelength-sensitive (S) cones. It is characterized by night blindness, cystoid maculopathy and degenerative changes of the vascular arcades. Mutations in the NR2E3 gene, which encodes a photoreceptor cell-specific nuclear receptor, cause this disease.","Nervous system disease"
"H00346","Extrinsic allergic alveolitis","Extrinsic allergic alveolitis (EAA), also known as hypersensitivity pneumonitis, is caused by repeated inhalation of mainly organic antigens by sensitized subjects. This induces a hypersensitivity response in the distal bronchioles and alveoli and subjects may present clinically with a variety of symptoms. EAA is caused by a wide variety of antigens including bacteria, organic materials, fungal spores, and chemicals. Of the various EAA syndromes, Farmer's lung and Bird fancier's disease are the commonest forms that have been studied. EEA is a complex dynamic clinical syndrome where clinical expression depends on the frequency and amount of contact with antigen and host susceptibility. The manifestations and symptoms can be complicated by self-regulatory measures performed by those affected individuals to reduce antigen exposure. There are many individuals with a positive antibody reaction who remain asymptomatic. EEA traditionally has been described as occurring in a state of acute, subacute, and chronic form.","Immune system disease; Respiratory disease; Infectious disease"
"H01294","Nephrogenic syndrome of inappropriate antidiuresis","Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a disorder of water balance caused by gain of function mutation of arginine vasopressin receptor type 2 (AVPR2) resulting in free water reabsorption and episodes of hyponatremia.","Endocrine disease; Urinary system disease"
"H02411","Chronic myelomonocytic leukemia","Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder associated with peripheral blood monocytosis, with an inherent risk for leukemic transformation. CMML has overlapping features of myelodysplastic syndromes (MDS) [DS:H01481] and myeloproliferative neoplasms (MPN). Gene mutations are seen in >90% of patients, with common abnormalities involving; epigenetic regulators (TET2  -60% and ASXL1 -40%), spliceosome components (SRSF2 -50%), transcription factors (RUNX1 -15%) and cell signaling (RAS -30%, CBL -15%).","Cancer"
"H00948","Renal hypouricemia","Renal hypouricemia (RHUC) is a disorder characterized by impaired uric acid reabsorption at the apical membrane of proximal renal tubule cells, and high urinary urate excretion. Renal urate reabsorption is controlled via two proximal tubular urate transporters: apical URAT1 (SLC22A12) and basolateral GLUT9 (SLC2A9). And it has been suggested that RHUC is caused by mutations in URAT1 or GLUT9. Most of patients were asymptomatic, but some had nephrolithiasis or were predisposed to exercise-induced acute renal failure.","Urinary system disease"
"H00174","Methylmalonic aciduria","Methylmalonic aciduria (MMA) is caused by a deficiency of methylmalonyl-CoA mutase (mut type), which is a vitamin B12-dependent enzyme. Defects of adenosylcobalamin metabolism lead to variant forms of MMA (cblA and cblB type).","Congenital disorder of metabolism; Nervous system disease"
"H01409","Methicillin-sensitive Staphylococcus aureus (MSSA) infection","Staphylococcus aureus is a Gram-positive human commensal bacterium persistently colonizing the anterior nares of about 30% of the human population. Methicillin-resistant S. aureus (MRSA) is known to have evolved from methicillin-susceptible S. aureus (MSSA) after acquiring the staphylococcal cassette chromosome mec (SCCmec) element which includes the mecA gene coding for resistance to the antibiotic methicillin. A highly cytotoxic and clinically virulent methicillin-sensitive strain, S. aureus strain 6850 is a well-characterized prototype strain isolated from a patient with a skin abscess which had progressed to S. aureus bacteremia, osteomyelitis, septic arthritis, and multiple systemic abscesses.","Infectious disease"
"H00983","Alpha-2-plasmin inhibitor (a2-PI) deficiency","Alpha-2-plasmin inhibitor (a2-PI) deficiency is an autosomal recessive disorder resulting in severe hemorrhagic diathesis. Mutations in SERPINF2 gene cause a2-PI deficiency. A2-PI acts as the primary inhibitor of plasminogen, and its deficiency causes a rare bleeding disorder because of increased fibrinolysis.","Hematologic disease"
"H01851","Congenital scoliosis associated with rib anomalies","Congenital scoliosis is a lateral curvature of the spine that is due to the presence of vertebral anomalies causing an imbalance in the longitudinal growth of the spine. Most congenital scoliosis is often recognized at birth, but more subtle spinal defects can remain undetected. A close interaction of genes and environment regulates the development of normal spine. Developmental studies in animal models have identified many genes regulating somite formation and segmentation. Patients with congenital scoliosis frequently have other associated anomalies. Sometimes rib fusion or absence can be observed along with the spinal anomalies since ribs are formed in close association with the vertebrae. When the number of ribs on the right or left side do not match, congenital vertebral anomalies should be suspected. An extensive thoracic congenital scoliosis associated with fused ribs may affect thoracic function and the growth of the lungs in young children and lead to a thoracic insufficiency syndrome. The vertebral expandable prosthetic titanium rib (VEPTR) holds the expanded hemithorax. This improves the thoracic height, lung volume and lung function.","Congenital malformation"
"H00977","Trichorhinophalangeal syndrome","Trichorhinophalangeal syndromes (TRPS) is a rare peripheral dysostosis with mainly autosomal dominant inheritance. Three different forms of TRPS are known: type I (TRPS1), type II (TRPS2) and type III (TRPS3). They are characterized by sparse hair, bulbous pear-shaped nose, long and flat philtrum, thin upper lip, and protruding ears. Skeletal abnormalities that are frequently observed include epiphyses of the middle phalanges with shortened metacarpals, hip malformations, and short stature. The causative gene is TRPS1 that was shown to be a regulator of the Wnt signaling pathway in mouse.","Congenital malformation"
"H01099","Trichinosis","Trichinellosis or trichinosis is a foodborne disease caused by the parasitic nematode Trichinella and is widely distributed in the temperate, tropical, and arctic regions. Humans become infected after eating larvae present in raw or inadequately cooked meat.","Infectious disease"
"H00379","Mosquito-borne viral encephalitis","Mosquito-borne viral encephalitides are infections of the central nervous system caused by arboviruses (arthropod-borne viruses) and transmitted by mosquitoes. Arboviruses are zoonotic viruses and consist of taxonomically different viruses, including flavivirus, alphavirus and bunyavirus.","Infectious disease"
"H02278","Jansky-Bielschowsky disease","Jansky-Bielschowsky disease, a classical late infantile neuronal ceroid lipofuscinosis (LINCL), is an autosomal recessive neurodegenerative disease with onset of symptoms between 2 and 4 years of age. Clinical symptoms include seizures, progressive encephalopathy, visual failure, and motor abnormalities. Mutations in the TPP1 gene, that encodes the lysosomal enzyme tripeptidyl-peptidase 1, cause this disease.","Congenital disorder of metabolism"
"H00173","Isovaleric acidemia","Isovaleric acidemia (IVA) is an autosomal recessive inborn error of leucine metabolism caused by a deficiency of the mitochondrial enzyme isovaleryl-CoA dehydrogenase resulting in the accumulation of derivatives of isovaleryl-CoA.","Inherited metabolic disease"
"H00341","Mycoplasma pneumonia","Mycoplasmas represent the smallest self-replicating organisms that are most closely related to the gram-positive bacterial group that includes streptococci, bacilli, and lactobacilli. Mycoplasma pneumoniae is a member of the family Mycoplasmataceae that causes both the upper and the lower respiratory tract infection both endemically and epidemically worldwide. Most infections are mild, but a small proportion of infected individuals may develop serious pneumonia due to an enhanced host cellular immune response.","Infectious disease"
"H01293","Narcolepsy","Narcolepsy is a disabling sleep disorder characterized by irresistible excessive daytime sleepiness and cataplexy, a condition triggered by strong emotions leading to a sudden loss of muscle tone. Narcolepsy is a rare and mainly sporadic disorder. Familial narcolepsy accounts for less than 10% of all narcolepsy cases, and causative mutations have not been identified to date. The discovery of hypocretin-1 (HCRT) deficiency shed light on the underlying pathophysiology of the disease. The hypocretin neurotransmission system was shown to play a major role in controlling vigilance states. Because of the strong HLA association, hypocretin deficiency is believed to be caused by an autoimmune attack. It has also been reported that a missense mutation in myelin oligodendrocyte glycoprotein (MOG) is the cause of narcolepsy.","Nervous system disease"
"H02416","Cimicosis","Cimicosis is an ectoparasitosis caused by the bite of bed bugs, belonging to the family Cimicidae. Although the Cimicidae comprises more than 90 species, only two species, Cimex lectularius and C. hemipterus, readily feed on humans. Evidence for disease transmission by this blood-sucking insect is lacking.","Infectious disease"
"H00725","Short QT syndrome","Short QT syndrome (SQTS) is a cardiovascular disorder resulting from mutations in cardiac ion channels. The mutation of genes (KCNH2, KCNQ1, and KCNJ2) encoding for cardiac potassium channels plays a central role in SQTS. SQTS is characterized by constantly short QT interval associated with atrial fibrillation, syncopal episodes, and sudden cardiac death. The implantable cardioverter defibrillator (ICD) therapy in patients with a short QT syndrome has an increased risk due to possible T wave oversensing.","Cardiovascular disease"
"H02072","Stickler syndrome","Stickler syndrome (STL) is a hereditary connective tissue disorder of fibrillar collagen. It is characterized by ocular signs (myopia, vitreoretinal degeneration, retinal detachment and cataracts), arthropathy, deafness, cleft palate, micrognathia, and a characteristic flat face. Mutations in the COL2A1, COL11A1, COL11A2, COL9A1, and COL9A2 genes can cause Stickler syndrome.","Congenital malformation"
"H02240","Ehlers-Danlos syndrome periodontal type","Ehlers-Danlos syndrome periodontal type (EDSPD) is an autosomal-dominant disorder characterized by early-onset periodontitis leading to premature loss of teeth, joint hypermobility, and mild skin findings. EDSPD is caused by mutations in C1R and C1S, which encode subcomponents C1r and C1s of complement.","Congenital malformation"
"H00517","Spondylocostal dysostosis","Spondylocostal dysostosis (SCDO) is a group of disorders characterized by vertebral defects along the entire spinal column with rib fusions and deletions. SCD arises from disturbed somite segmentation during embryonic development due to mutations in Notch pathway genes.","Congenital malformation"
"H01603","Primary aldosteronism","Primary aldosteronism is a clinical syndrome characterized by excess secretion of aldosterone from the adrenal gland. It is manifested by hypertension and hyporeninemia. In the past, hypokalemia was thought to be a mandatory finding in primary aldosteronism. However, later studies confirmed that most patients with primary aldosteronism are normokalemic. The prevalence of primary aldosteronism among nonselected hypertensive persons is between 5% and 13%, and it is now recognized to be the most common form of secondary hypertension. There are the seven subtypes of primary aldosteronism. Aldosterone-producing adenoma (APA) and bilateral idiopathic hyperaldosteronism (IHA) are the most common subtypes of primary aldosteronism. Unilateral adrenal hyperplasia, aldosterone-producing adrenocortical carcinoma, ectopic aldosterone-producing adenoma, and familial hyperaldosteronism (type I and typeII) are unusual subtypes. Somatic mutations in KCNJ5, ATP1A1, ATP2B3, and CACNA1D have been described in APAs. Usually, adenomas are managed surgically and bilateral hyperplasia, medically.","Endocrine disease"
"H02086","Mitochondrial complex III deficiency","Mitochondrial complex III deficiency (MC3DN) is a relatively rare devastating disorder that impairs energy generation, and leads to variable symptoms such as developmental regression, seizures, kidney dysfunction and frequently death. Until now, mutations in nine genes have been known to cause CIII deficiency. CYC1, UQCRB, UQCRQ, and UQCRC2 encode components of CIII itself, whereas BCS1L, TTC19, LYRM7, UQCC2, and UQCC3 produce mitochondrial assembly factors.","Congenital disorder of metabolism"
"H01431","Cushing syndrome","Cushing syndrome (CS) is a rare disorder resulting from prolonged exposure to excess glucocorticoids via exogenous and endogenous sources. The typical clinical features of CS are related to hypercortisolism and include accumulation of central fat, moon facies, neuromuscular weakness, osteoporosis or bone fractures, metabolic complications, and mood changes. Traditionally, endogenous CS is classified as adrenocorticotropic hormone (ACTH)-dependent (about 80%) or ACTH- independent (about 20%). Among ACTH-dependent forms, pituitary corticotroph adenoma (Cushing's disease) is most common. Most pituitary tumors are sporadic, resulting from monoclonal expansion of a single mutated cell. Recently recurrent activating somatic driver mutations in the ubiquitin-specific protease 8 gene (USP8) were identified in almost half of corticotroph adenoma. Germline mutations in MEN1 (encoding menin), AIP (encoding aryl-hydrocarbon receptor-interacting protein), PRKAR1A (encoding cAMP-dependent protein kinase type I alpha regulatory subunit) and CDKN1B (encoding cyclin-dependent kinase inhibitor 1B; also known as p27 Kip1) have been identified in familial forms of pituitary adenomas. However, the frequency of familial pituitary adenomas is less than 5% in patients with pituitary adenomas. Among ACTH-independent CS, adrenal adenoma is most common. Rare adrenal causes of CS include primary bilateral macronodular adrenal hyperplasia (BMAH) or primary pigmented nodular adrenocortical disease (PPNAD).","Endocrine and metabolic disease"
"H01869","Megacystis microcolon intestinal hypoperistalsis syndrome","Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a rare congenital anomaly with decreased muscular tone in the urinary tract and intestine. MMIHS is characterized by prenatal-onset distended urinary bladder with functional intestinal obstruction. Hypoperistalsis causes a pseudo-obstruction which leads to a shortened and malrotated microcolon and food intolerance. MMIHS usually affects women, and is almost lethal in the first year of life. Although pro-kinetic agents and alimentation have prolonged life in some cases, but the long term outcome remains poor. Extensive surgical intervention is required for survival. Pathogenesis of MMIHS remains unclear but impaired peristalsis seems to be owing to abnormal ganglion cells pattern and absence of interstitial Cajal cells. While it is believed to be an autosomal recessive disorder, most cases are sporadic. It has been identified de novo ACTG2 mutations cause MMIHS.","Congenital malformation"
"H00187","Ornithine transcarbamylase deficiency","Ornithine transcarbamylase deficiency, the most common urea cycle defect, results in failure to thrive, hypotonia, seizures and mental retardation.","Inherited metabolic disease; Nervous system disease"
"H01055","Giant kidney worm infection","Dioctophyma renale is a parasite of the Dioctophymidae family that principally occurs in dogs or other carnivores. Humans are accidental definitive hosts. Ingested Dioctophyma larvae migrate into the right kidney where they mature. Clinical presentation of D. renale infection is unspecific.","Infectious disease"
"H01267","Familial hyperinsulinemic hypoglycemia","Familial hyperinsulinemic hypoglycemia (HHF) is the most common cause of persistent hypoglycemia in infancy. Recent studies on the molecular basis of the disease have disclosed specific genetic defects in the regulation of insulin secretion. Seven different loci have been associated with hyperinsulinism: ABCC8, KCNJ11, HADHSC, GCK, GLUD1, SLC16A1, and INSR. Mutations of these loci have significant differences in phenotype and inheritance pattern. The most common genes associated with hyperinsulinism, involve the ABCC8 and KCNJ11 genes that encode the two subunits of the beta-cell ATP-dependent potassium channel. Recessive mutations of these genes cause a severe form of neonatal hypoglycemia that frequently requires near-total pancreatectomy. Diazoxide, a drug that acts as an agonist of the ATP-dependent potassium channel to suppress insulin secretion, is effective in defects associated with mutations of GLUD1 and HADHSC. Diazoxide is often ineffective in mutations of the ATP- dependent potassium channel and may not adequately control hypoglycemia in GCK or SLC16A1 mutations.","Inherited metabolic disease"
"H00528","Frontonasal dysplasia","Frontonasal dysplasia is a rare developmental field defect with separation or clefting of the central portion of the face. Its basic characteristics include hypertelorism, a broad nose, or complete midline splitting of the nose.","Congenital malformation"
"H02429","Actinic keratosis","Actinic keratosis (AK) is a common cutaneous lesion associated with chronic exposure to ultraviolet (UV) radiation. AK presents scaly, erythematous papule or plaque and is considered the earliest clinically recognizable manifestation of squamous cell carcinoma.","Skin disease"
"H00970","Juvenile primary lateral sclerosis","Juvenile primary lateral sclerosis is a very rare progressive paralytic disorder characterized by increasing weakness and stiffness of muscles in the arms, legs and face. Although primary lateral sclerosis (PLS) is a sporadic disorder of adult middle age, this disease is also observed in children as JSPS. JSPS arises from dysfunction of the upper motoneurons and the causative gene is ALS2.","Neurodegenerative disease"
"H01258","Generalized epilepsy and paroxysmal dyskinesia","Epilepsy is one of the most common and debilitating neurological disorders, and paroxysmal dyskinesia is another heterogeneous group of neurological disorders characterized by sudden, unpredictable, disabling attacks of involuntary movement often requiring life-long treatment. It has been reported that a mutation of the alpha subunit of the BK channel causes a syndrome of coexistent epilepsy and paroxysmal dyskinesia, which is called generalized epilepsy and paroxysmal dyskinesia (GEPD).","Nervous system disease"
"H00984","Bare lymphocyte syndrome type1","Bare lymphocyte syndrome (BLS) is a rare recessive genetic immune disorder endorsed by a partial or complete absence of major histocompatibility complex (MHC) or human leukocyte antigen (HLA) expression. BLS could be grouped as Type I, Type II and Type III based on defective surface MHC expression. The mutations in the TAP subunits are one of the most common features of BLS type I. MHC I deficiency due to tapasin (TAPBP) deficiency was also discovered recently.","Inherited metabolic disease; Immune system disease"
"H01856","Cloacal exstrophy","Cloacal exstrophy is an extremely rare congenital complex deformity that is associated with anterior abdominal wall defects, reflex and exposure of the cloaca (uninterrupted ureter and bowel), aproctia, a widely separated pubic bone, and defects or dysplasia of external genital organs. Cloacal exstrophy is thought to be related to abnormal development of the cloacal membrane, a transitory structure composed of endoderm and ectoderm that overlies the embryonic cloaca. The result is primarily an abdominal wall defect with failed closure of the lower urinary tract. Cloacal exstrophy has also been referred to as the OEIS complex (omphalocele, exstrophy, imperforate anus and spinal defect), and other malformations of the urogenital, gastrointestinal, skeletal and neurospinal axis frequently coexist.","Congenital malformation"
"H01835","Neuronal migration disorder","Neuronal migration disorders (NMD) are developmental malformations of the cerebral hemispheres, frequently associated with severe epilepsy. They can be defined as cerebral malformations characterised by malpositioning and faulty differentiation of cortical grey matter. Neuronal positioning is an integral part of the coordinated steps comprising neural circuit formation in embryonic and neonatal development. Correct positioning of neurons by normal migration plays a critical role in establishing cognitive functions and emotion. The causes of brain malformations associated with positioning and migration defects are varied and include genetic mutations and environmental toxins. Studies of neuronal migration disorders have progressed due to advances in molecular genetics and brain magnetic resonance imaging.","Congenital malformation"
"H01009","Newfoundland rod-cone dystrophy","Newfoundland rod-cone dystrophy (NFRCD) is a disorder characterized by retinal dystrophy reminiscent of retinitis punctata albescens with a substantially lower age at onset and more-rapid and distinctive progression. Mutations in RLBP1 gene, encoding the cellular retinaldehyde-binding protein, are likely to cause NFRCD.","Nervous system disease"
"H00913","Brain-lung-thyroid syndrome","Choreoathetosis, hypothyroidism, and neonatal respiratory distress is a syndrome of congenital hypothyroidism associated with pulmonary problems, mental retardation, muscular hypotonia and persistent ataxia which could be described as choreoathetosis. This disorder is attributed to mutations of the NKX2.1, a homeodomain transcription factor expressed in the developing thyroid, respiratory epithelium, and specific areas of the forebrain during embrypgenesis.","Endocrine and metabolic disease"
"H01499","Sporotrichosis","Sporotrichosis is an endemic mycosis in tropical and subtropical areas caused by Sporothrix schenckii which is a common saprophyte of soil, decaying wood, hay and sphagnum moss. S. schenckii usually causes a mixed suppurative and granulomatous inflammatory reaction in the dermis and subcutaneous tissue, frequently accompanied by microabscess and fibrosis. The most common symptom is cutaneous disease, which is classified into fixed and lymphocutaneous forms. Osteoarticular, pulmonary, mucosal, disseminated and systemic infections are less common and usually occur in immunosuppressed individuals.","Infectious disease"
"H00779","Usher syndrome (US)","Usher syndrome (USH) is a group of autosomal recessively inherited disorders characterized by deafness and vision loss. Three clinical types USH1, USH2, and USH3, are distinguished on the basis of severity of hearing loss and the presence or absence of vestibular dysfunction. USH1 patients are congenitally profoundly deaf, and have vestibular dysfunction as well as prepubertal onset of progressive retinitis pigmentosa (RP). USH2 is characterized by congenital mild hearing impairment with normal vestibular responses. USH3 is characterized by a progressive hearing loss, a variable vestibular dysfunction, and RP. USH shows significant genetic heterogeneity, and at least 11 distinct loci have been identified and genes for 9 of them have been cloned.","Nervous system disease"
"H01036","Posterior column ataxia with retinitis pigmentosa","Posterior column ataxia with retinitis pigmentosa (PCARP) is an autosomal recessive, childhood onset neurodegenerative disorder characterized by sensory ataxia and retinitis pigmentosa. It has been reported that PCARP is caused by mutations in FLVCR1, a gene encoding a heme-transporter protein.","Nervous system disease"
"H01204","Cerebellar ataxia, mental retardation (MR), and dysequilibrium syndrome (CAMRQ)","Cerebellar ataxia, mental retardation (MR), and dysequilibrium syndrome (CAMRQ) is autosomal recessive, genetically heterogeneous conditions characterized by early onset of cerebellar ataxia and MR. Patients with CAMRQs have a severe disturbance of posture and balance, strabismus, muscular hypotonia during childhood and they have a delayed ability to walk independently. The disease is also characterized by perceptual difficulties and in most cases mild mental retardation. Four subtypes have been mapped so far.","Nervous system disease"
"H02481","Syndromic disorder with short stature","Short stature is one of the major components of many dysmorphic syndromes. Growth failure may be due to a wide variety of mechanisms, either related to the growth hormone (GH) or to underlying unknown pathologies. Several underlying genetic causes of these disorders have been identified.","Congenital malformation"
"H01660","Pityriasis rosea","Pityriasis rosea (PR) is an acute exanthem, which prevalently affects children and young adults. The cause of PR is uncertain but epidemiological (seasonal variation and clustering in communities) and clinical features suggest an infective agent. Light and electron microscopy findings suggest infection with human herpesviruses 6 and 7 (HHV-6/7). HHV-6 and HHV-7 may also interact with each other, explaining recurrences and atypical presentations. PR is self limiting and resolves within one to three months. It typically starts with the development of a large erythematous scaly plaque also called the herald patch or mother patch on trunk or neck, which is followed by an eruption of multiple secondary small erythematous scaly lesions located predominantly on the trunk and following the lines of cleavage on the back (Christmas tree or inverted fir tree appearance). Collarette scaling is seen typically. The eruption is usually preceded by a prodrome of sore throat, gastrointestinal disturbance, fever, and arthralgia. A case of PR is diagnosed mainly on clinical grounds. A biopsy is needed in atypical cases, and it mainly helps in excluding other differentials rather than diagnosing PR as the histopathological examination in a case of PR is relatively nonspecific and resembles a subacute or chronic dermatitis. As PR is a self-limiting disorder, most patients just need to be counseled regarding the natural course of the disease instead of putting them on an aggressive treatment protocol. Most patients would just need emollients, antihistaminics, and sometimes topical steroids to control pruritus.","Skin and connective tissue disease"
"H00580","Schimke immunoosseous dysplasia","Schimke immunoosseous dysplasia is an autosomal recessive disorder characterized by spondyloepiphyseal dysplasia resulting in a short-trunk disproportionate dwarfism, T cell immunodeficiency, and progressive nephropathy with focal segmental glomerulosclerosis.","Congenital malformation"
"H01452","Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection","Pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) is an autoimmune disorder presenting with obsessive compulsive disorder and/or tics. PANDAS is believed to be caused by antibodies generated in response to a group A beta-hemolytic streptococcal (GAS) infection in genetically susceptible individuals. PANDAS is defined by five diagnostic criteria: (1) the presence of OCD and/or a tic disorder, (2) prepubertal symptom onset, (3) an abrupt onset of symptoms that are episodic in severity, (4) a temporal association between symptom exacerbations and GAS infections, and (5) the presence of neurological abnormalities (e.g., choreiform movements) during exacerbations. It has been reported that antibiotics and immunomodulatory therapies (plasma exchange and IVIG) were effective in lessening of symptom severity.","Immune system disease; Mental and behavioural disorders"
"H00746","Hypokalemic periodic paralysis (HypoPP)","Hypokalemic periodic paralysis (HypoPP) is a member of periodic paralyses, an autosomal dominant genetic disorders caused by mutations in the sodium, potassium, and calcium channel genes in skeletal muscle. In general, HypoPP is characterized by reversible attacks of muscle weakness concomitant with decreased blood potassium concentrations. HypoPP is associated with point mutations in both CACNA1S (HypoPP1) and SCN4A (HypoPP2).","Nervous system disease; Musculoskeletal disease; Congenital disorder of metabolism"
"H01694","Stevens-Johnson syndrome","Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe acute mucocutaneous diseases. The early stage of the disease is characterized by red-purple maculopapular eruptions. Then epidermal separation occurs and vesicles and bullae are formed. Inflammatory changes including purulent conjunctivitis, erosion, ulcer and crusts may be observed in the eye, mouth, nose, pharynx, esophagus, trachea, gastrointestinal tract, urinary tract and genital mucosae. Life-threatening bleeding and infections may be observed as a result of these changes. The rates of severe complications or sequelae secondary to SJS and TEN are higher in patients with mucosal and ophthalmic involvement. The SJS and TEN are considered the same disease process, and the distinction is made based on body surface area involvement. The SJS is characterized by less than 10% of the body surface area of epidermal detachment, and TEN by more than 30%. Various etiologic factors have been implicated as causes of SJS-TEN. These include infection, vaccination, drugs, systemic diseases, physical agents, and food. Drugs are the most commonly blamed. It has been reported that SJS-TEN is strongly associated with the specific variants of the human leukocyte antigen HLA-A and HLA-B genes. There is still no consensus on a definite treatment method for SJS-TEN. Systemic steroids and IVIG are used most frequently in medical treatment and treatment options including cyclosporine, plasmapheresis and hemodialysis are required more rarely.","Skin and connective tissue disease"
"H02011","Familial juvenile hyperuricemic nephropathy","Familial juvenile hyperuricemic nephropathy (FJHN) is an autosomal dominant disorder, which is characterized by elevated serum uric acid concentrations due to a low fractional excretion of uric acid (FEUA), defective urinary concentrating ability, interstitial nephropathy, and progression to end-stage renal failure. Recently, new terminology using the term autosomal dominant tubulointerstitial kidney disease (ADTKD) has been proposed, and FJHN is encompassed by it.","Kidney disease"
"H02223","Osteocraniostenosis","Osteocraniostenosis, also known as gracile bone dysplasia (GCLEB), is a perinatally lethal condition characterized by gracile bones with thin diaphyses, premature closure of basal cranial sutures, and microphthalmia. It has been reported that individuals with GCLEB had mutations in FAM111A.","Congenital malformation"
"H00574","Coffin-Lowry syndrome","Coffin-Lowry syndrome (CLS) is a syndromic form of X-linked mental retardation, which is characterized in male patients by psychomotor and growth retardation and various skeletal anomalies. Typical facial changes and specific clinical and radiological signs in the hand are useful aids in the diagnosis. Mutations in the RSK2 (RPS6KA3) gene cause CLS. The RPS6KA3 gene encodes RSK2 that is involved with signaling within cells.","Congenital malformation"
"H00110","Cholera","Cholera is an infection of the small intestine caused by toxigenic strains of Vibrio cholerae, mostly belonging to the O1 serogroup but also to the O139 serogroup. Seven cholera pandemics have occurred since 1817, with six pandemics originating in India and the seventh pandemic originating in Indonesia in 1961. The last outbreak is dominated by an O1 variant named El Tor and has continued to the present. The O139 serogroup was first observed in 1992 in India and associated with epidemics in localized areas.","Infectious disease"
"H00322","Epidemic typhus","Epidemic typhus is caused by gram-negative rickettsia species in the typhus biogroup that are transmitted by infective louse and flea. The disease is widely distributed in tropical and subtropical areas. Most patients present with an acute febrile disease with constitutional symptom and maculopapular exanthema.","Infectious disease"
"H02475","Retinoschisis","Retinoschisis (RS) is a retinal disorder with macular degeneration. In most cases, juvenile retinoschisis is transmitted as an X-linked recessive trait. The RS1 gene responsible for X-linked juvenile retinoschisis (XLRS) was discovered by positional cloning.","Congenital malformation"
"H02029","Mycobacterium avium complex (MAC) pulmonary disease","Nontuberculous mycobacteria (NTM), including Mycobacterium avium complex (MAC), cause opportunistic chronic pulmonary infections. MAC includes M. avium, M. intracellulare, and eight other species, including M. chimaera. MAC pulmonary disease has been described with two types of clinical manifestations: fibrocavitary and nodular bronchiectatic.","Infectious disease"
"H00914","Warsaw breakage syndrome","Warsaw breakage syndrome is a cohesinopathy characterized by cellular defects in sister chromatid cohesion and hypersensitivity to agents that induce replication stress. It is caused by defective DDX11/ChlR1, a XPD helicase family member. In Warsaw breakage syndrome, features of Fanconi anemia (chromosomal breakage) and Roberts syndrome (sister chromatid cohesion defects) coexist, and individuals with this disorder show severe microcephaly, facial dysmorphy, pre- and post- natal growth retardation, and abnormal skin pigmentation.","Congenital malformation"
"H00128","Mucopolysaccharidosis type I","Mucopolysaccharidosis type I (MPS1) is an autosomal recessive lysosomal storage disorder caused by deficient activity of alpha-L-iduronidase in glycosaminoglycan degradation. The enzyme defect results in the accumulation of heparan sulfate and dermatan sulfate in many organs, as well as elevated metabolite levels in urine. Hurler syndrome is characterized by coarse faces, hydrocephalus, dysostosis multiplex, cardiac valve disease, airway obstruction, and mental retardation. Scheie syndrome is a milder form.","Inherited metabolic disease; Lysosomal storage disease"
"H01832","Lenz-Majewski syndrome","Lenz-Majewski syndrome (LMS), also known as Lenz-Majewski hyperostotic dwarfism, is an extremely rare syndrome characterized by osteosclerosis, intellectual disability, characteristic facies, and distinct craniofacial, dental, cutaneous and distal-limb anomalies. Mutations in the PTDSS1 gene coding one of the phosphatidylserine (PS) synthase enzymes, PSS1, have been described as causative in LMS patients. Such mutations render PSS1 insensitive to feedback inhibition by PS levels.","Congenital malformation"
"H01658","Microscopic polyangiitis","Microscopic polyangiitis (MPA) is an idiopathic autoimmune disease characterized by systemic vasculitis. MPA predominantly affects small-calibre blood vessels and is associated with the presence of antineutrophil cytoplasmic autoantibodies (ANCA). The association with ANCAs originally defined the group of ANCA-associated vasculitides, comprising granulomatosis with polyangitis (GPA, formerly known as Wegener granulomatosis) [DS:H01655], microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA, formerly known as Churg-Strauss syndrome) [DS:H01468], which have different frequencies of ANCA-positivity. ANCA in MPA are predominantly directed against myeloperoxidase (MPO-ANCA) but may, in a minority of patients, be directed against proteinase 3 (PR3-ANCA). Not all patients, however, have ANCA. MPA is clinically characterized by small-vessel vasculitis primarily affecting the kidneys and the lungs but other organs may be involved as well. Renal involvement, which can be the only manifestation, is clinically apparent as rapidly progressive glomerulonephritis and histopathologically as pauci-immune necrotizing and crescentic glomerulonephritis. Diagnosis is mainly established by clinical manifestations, computed tomography (TC), ANCA antibody detection, and renal and pulmonary biopsy. The introduction of aggressive immunosuppressive treatment has substantially improved the prognosis. The standardized therapeutic regimen is based on cyclophosphamide and corticosteroids. Using this regimen, remission can be achieved in most of the patients. Rituximab may represent an important alternative to cyclophosphamide for patients who may not respond adequately to antimetabolite therapies.","Nervous system disease; Cardiovascular disease; Immune system disease"
"H00325","Brucellosis","Brucellosis is a zoonotic disease of worldwide distribution that mainly affects persons working with domestic animals. Although many countries have eradicated Brucella abortus from cattle, Brucella melitensis remains a major cause of infection in cattle and human in Latin America, the Middle East, Spain, parts of Africa, and western Asia. Consumption of contaminated foods is the sources of infection. The clinical presentation can vary from asymptomatic infection to a fever, night sweats, and joint manifestations.","Infectious disease"
"H02472","Early-onset progressive encephalopathy","Early-onset progressive encephalopathy with brain atrophy and spasticity (PEBAS) is caused by mutations in TRAPPC12. Changes in Golgi morphology, membrane trafficking dysfunction, and mitotic delay were reported in fibroblasts of patients.Early-onset progressive encephalopathy with episodic rhabdomyolysis (PEERB) is caused by mutations in TRAPPC2L. Both TRAPPC2L and TRAPPC12 are members of the TRAPP protein complex, which functions in membrane trafficking.","Nervous system disease"
"H00117","Primary hyperoxaluria","Primary hyperoxaluria (PH) is an autosomal recessive disorder characterized by the overproduction of oxalate.","Inherited metabolic disease"
"H02224","Grange syndrome","Grange syndrome comprises arterial stenoses with hypertension, brachysyndactyly, bone fragility, learning disability, and cardiac defects. It has been reported that mutations in YY1AP1 lead to Grange syndrome.","Congenital malformation"
"H00573","Townes-Brocks syndrome","Townes-Brocks syndrome is an autosomal dominant disorder. Characteristic features of the disease include external ear anomalies called microtia, hearing loss, hand anomalies like preaxial polydactyly/triphalangeal thumbs, imperforate anus and renal malformations.","Congenital malformation"
"H00741","Ichthyosis prematurity syndrome","Ichthyosis prematurity syndrome is a form of syndromic congenital ichthyosis characterized by the premature birth, neonatal asphyxia, and epidermal cornification with desquamation. Patients with this disease harbor mutations in the gene encoding the fatty acid transport protein 4 (FATP4).","Congenital malformation"
"H01693","Eosinophilic fasciitis","Eosinophilic fasciitis (EF) is a systemic inflammatory disease characterized by symmetrical swelling and skin induration of the arms and/or legs, evolving into a scleroderma-like appearance, accompanied by peripheral blood eosinophilia. The disease is present almost equally in both sexes. The etiology of EF remains uncertain. Hematological, infectious, and autoimmune diseases, as well as intense physical exertion, chemical compounds, drugs, solid neoplasms, and physical factors have been proposed as possible triggers and associated factors. Some researchers have proposed an aberrant immune response as the main pathogenetic mechanism. Some EF patients improve spontaneously without treatment, but in those who do not, glucocorticoids are the mainstay therapy. Methotrexate at low doses is probably the most favored second-line treatment, especially in patients with morphea-like skin lesions.","Musculoskeletal disease"
"H02016","Tay-Sachs disease","Tay-Sachs disease is an autosomal recessive lysosomal storage disorder caused by mutations in HEXA that encodes beta hexosaminidase subunit alpha. In the absence of hexosaminidase A, GM2 ganglioside cannot be hydrolyzed and therefore accumulates primarily in neuronal tissues. This results in progressive neurologic degeneration. Patients with infantile Tay-Sachs disease die before the age of five, whereas patients with the juvenile and adult forms have a delayed onset.","Inherited metabolic disease; Lysosomal storage disease"
"H00587","Epidermolysis bullosa, dysprophica","Inherited epidermolysis bullosa is a diverse group of disorders characterized by mechanically fragile skin that readily blister. The dystrophic forms of epidermolysis bullosa, in which tissue separation occurs in the dermis, are inherited in either autosomal dominant or autosomal recessive pattern. In the most severe subtype of recessive dystrophic epidermolysis bullosa, there is esophageal stenosis and pseudosyndactyly.","Congenital malformation"
"H01455","Necrotizing fasciitis","Necrotizing fasciitis (NF) is a severe life-threatening soft tissue infection characterized by rapidly spreading necrosis of the fascia and the subcutaneous tissue. Although more common in adults, NF also affects the pediatric population. Many bacterial organisms can cause NF, but group A Streptococcus is the most common monomicrobial cause of disease. Other bacterial pathogens that have been implicated in NF include Staphylococcus aureus, Clostridium species, and mixed Gram-negative and anaerobic organisms.","Infectious disease"
"H01667","Medulloblastoma","Medulloblastoma is the most common embryonal CNS tumor of childhood and is likely composed of biologically different subsets of tumors arising from stem and/or progenitor cells of the cerebellum. Recently, four distinct molecular subgroups of medulloblastoma have been identified [WNT (wingless), SHH (sonic hedgehog), Group 3, and Group 4]. Nearly all (90 %) of WNT patients have somatic missense mutations in CTNNB1 which promote protein stabilization. Alterations in SHH subgroup most often fall within the Shh signalling pathway. The most common are somatic or germline inactivating alterations or loss of PTCH1 and SUFU, or somatic missense mutations activating SMO. Group 3 tumors are characterized by MYC amplification resulting in high MYC mRNA expression levels compared with SHH and Group 4 tumors.The most frequently mutated somatic gene in Group 4 medulloblastoma is KDM6A, a histone H3 Lys27 (H3K27) demethylase.","Cancer"
"H01203","Primary congenital glaucoma","Primary congenital glaucoma (PCG) is a severe form of glaucoma that presents early in life. PCG results from developmental abnormalities that affect the aqueous humor outflow pathway. PCG clinical features include elevated IOP, corneal edema, enlargement of the globe (buphthalmos), corneal enlargement, rupture of Descemet's membrane, and optic nerve damage. Two genes have been reported to cause PCG, CYP1B1 and LTBP2. Both genes cause a recessive form of this disease.","Congenital malformation"
"H02486","HELIX syndrome","HELIX syndrome is characterized by hypohidrosis, electrolyte imbalance, lacrimal gland dysfunction, ichthyosis, and xerostomia. It has been reported that mutations in CLDN10 cause HELIX syndrome.","Skin disease"
"H01031","Orthostatic intolerance","Orthostatic intolerance (OI) or postural tachycardia syndrome (POTS) is a disorder of the autonomic nervous system primarily affecting young females, and is characterized by lightheadedness, palpitations, fatigue, altered mentation, and syncope primarily occurring with upright posture and being relieved by lying down. Patients often have high plasma norepinephrine (NE) concentrations in relation to sympathetic outflow on standing. Abnormal norepinephrine transporter (NET) function is considered to contribute to the pathophysiology in some patients with OI. The impaired uptake of NE could be caused by a mutation in the SLC6A2 gene that encodes the NET.","Cardiovascular disease"
"H00922","Schinzel-Giedion midface retraction syndrome","Schinzel-Giedion midface retraction syndrome is a rare congenital disorder characterized by severe mental retardation, midface retraction, cardiac and urogenital malformations, skeletal malformations, and neuroepithelial neoplasia. The disorder is lethal and respiratory failure is the major cause of death.","Congenital malformation"
"H00748","Andersen-Tawil syndrome","Andersen-Tawil syndrome (ATS) is a distinct type of periodic paralysis characterized in its full form by a triad of cardiac abnormalities, distinctive facial and skeletal features, and periodic paralysis. The distinctive physical features considered characteristic of ATS are: broad forehead, hypoplastic mandible, hypotelorism, low-set ears, digit clinodactyly, and 2-3 syndactyly of the toes. It is obvious that ATS has a high degree of phenotypic heterogeneity. ATS patients have loss-of-function mutations in the KCNJ2 gene, which encodes the voltage-gated inward rectifier potassium channel, Kir2.1. However, described KCNJ2 mutations only account for approximately 60% of diagnoses, suggesting genetic heterogeneity.","Nervous system disease; Musculoskeletal disease; Congenital disorder of metabolism"
"H01804","Isaacs syndrome","Isaacs syndrome is a rare neuromuscular disorder of continuous muscle fibre activity resulting from peripheral nerve hyper excitability. Symptoms commonly include myokymia, pseudomyotonia, muscle cramps and stiffness. It is caused by voltage-gated potassium channel dysfunction and may be inherited or acquired. Recent evidences suggest that autoantibodies against voltage-gated potassium channels (VGKC-Abs) are associated with this disease. Treatment commonly includes anticonvulsants, immunosuppressive therapy and plasma exchange.","Nervous system disease; Musculoskeletal disease"
"H01038","Cerebellar ataxia cayman type","Cerebellar ataxia cayman type (ATCAY) is an autosomal recessive disorder characterized by hypotonia, mental retardation, and cerebellar dysfunction with marked cerebellar hypoplasia. It has been reported that mutation of the ATCAY gene encoding Caytaxin causes ATCAY by interfering with normal splicing.","Nervous system disease"
"H01497","Temtamy preaxial brachydactyly syndrome","Temtamy preaxial brachydactyly syndrome (TPBS) is an autosomal recessive rare disorder that is caused by the mutations in the CHSY1 gene. CHSY1 encodes chondroitin synthase 1 involving in the biosynthesis of chondroitin sulfate and perhaps affecting bone morphogenetic protein (BMP) signaling. The loss-of-function mutations in the protein cause defects in multiple development processes. The major features include limb malformations, short stature, hearing loss, delayed motor and mental development, facial dysmorphism and dental anomalies.","Congenital disorder of metabolism; Congenital malformation"
"H00545","Polycystic liver disease","Isolated polycystic liver disease is an inherited disorder in which cysts occur only in the liver without renal involvement. The two genes, PRKCSH, encoding hepatocystin, and SEC63, are found in patients with isolated polycystic liver disease.","Congenital malformation"
"H02212","Familial infantile myoclonic epilepsy","Familial infantile myoclonic epilepsy (FIME) is a rare autosomal recessive idiopathic epilepsy. Idiopathic epilepsies are a group of disorders characterized by recurrent seizures in the absence of detectable brain lesions or metabolic abnormalities. Recently, mutations in TBC1D24, an ARF6-interacting protein, have been described as the cause of FIME. The main recognized function of ARF6 in the nervous system is the regulation of dendritic branching, spine formation, and axonal extension.","Nervous system disease"
"H02020","Aromatase deficiency","Aromatase deficiency is a rare autosomal recessive syndrome, caused by mutations in CYP19A1 gene. Aromatase, encoded by the CYP19A1, catalyses the biosynthesis of estrogens. Due to estrogen deficiency, disorders of sex development and progressive virilization at puberty develop in females. In the males, prepubertal development is normal. Delayed epiphyseal closure, eunuchoid body habitus, osteopenia, and osteoporosis develop in both genders.","Endocrine disease"
"H00777","SEMD, short limb-hand type","Spondylometaepiphyseal dysplasia, short limb-hand type, or spondylometaepiphyseal dysplasia, short limb-abnormal calcification type is a rare skeletal dysplasia. The key clinical features of this condition include short stature with typical short hands and broad, puffy fingers, a narrow chest, and a characteristic craniofacial appearance. Their long bones are short due to premature epiphyses and irregular metaphyses.","Congenital malformation"
"H02444","Luscan-Lumish syndrome","Luscan-Lumish syndrome is an overgrowth condition caused by mutations in SETD2. It is characterised by macrocephaly, intellectual disability, speech delay, and behavioral problems.","Congenital malformation"
"H00313","Multidrug-resistant Pseudomonas aeruginosa infection","Pseudomonas aeruginosa is an opportunistic pathogen that may cause severe invasive diseases in critically ill patients. In the 21st century, when the life expectancy of highly susceptible immunocompromised groups has been extended in most countries, P. aeruginosa plays an increasingly prominent role in hospital infections. This organism shows a remarkable capacity to resist antibiotics, either intrinsically (because of constitutive expression of beta-lactamases and efflux pumps, combined with low permeability of the outer-membrane) or following acquisition of resistance genes (e.g., genes for beta-lactamases, or enzymes inactivating aminoglycosides or modifying their target), over-expression of efflux pumps, decreased expression of porins, or mutations in quinolone targets. These mechanisms mediate the multidrug-resistant (MDR) phenotype in P. aeruginosa.","Infectious disease"
"H01235","Bleeding disorder platelet-type","Bleeding disorder platelet-type is a condition characterized by mild to moderate mucocutaneous bleeding. Patients are with platelet dysfunction but normal platelet number. It has been reported that these disorders are associated with mutations in key platelet activation receptors, namely those for ADP, collagen and thromboxane A2.","Hematologic disease"
"H01007","Choroid plexus papilloma","Choroid plexus tumors (CPTs) are rare intraventricular papillary neoplasms of neuroectodermal origin, accounting for less than 1% of all intracranial tumors and 2-4% of pediatric brain tumors. CPTs are categorized by three distinct histologies; choroid plexus papilloma, atypical choroid plexus papilloma, and the malignant choroid plexus carcinoma. Choroid plexus papillomas outnumber choroid plexus carcinomas and are composed of a single layer of cuboidal-to-columnar cells, resting on a basement membrane overlying papillary and vascularized connective tissue.","Nervous system disease"
"H01463","Mycosis fungoides","Mycosis fungoides (MF) is the most common type of primary cutaneous T-cell lymphomas (CTCL), which are a heterogeneous group of malignancies derived from skin-homing T cells. MF presents in the skin with erythematous patches, plaques, and less frequently, tumours. Although the aetiologies of MF are unknown, important insights have been gained in the immunological and genetic perturbations that are associated with these diseases. Mutations in the p53, p15, p16, JunB, and PTEN genes generally occur in later-stage disease. Loss of normal apoptotic T-cell pathways has also been reported. Apoptosis is partly mediated by death receptors, notably Fas, which is part of the tumor necrosis factor family of receptors. Decreased and/or defective Fas expression by neoplastic T cells has been associated with advanced/aggressive disease and impaired Fas-mediated apoptosis.","Cancer"
"H01651","Macular edema","Macular edema is a common feature of many diseases of the retina, such as intraocular inflammation (uveitis), central or branch retinal vein occlusion, diabetic retinopathy and following cataract extraction. It is characterized by a retinal thickening in the macular area due to the breakdown of the blood-retinal barrier. Extracellular fluid accumulates in the intraretinal area or collects in the subretinal space. In more severe cases, it occurs as cystoid edema with the typical petaloid appearance, and is the leading cause of visual loss. New treatments for macular edema have emerged over the past decade, the most recent and efficacious of which have involved blockage of vascular endothelial growth factor (VEGF) by frequent intravitreal injection of pharmacologic agents.","Nervous system disease"
"H00783","Febrile seizures","Febrile seizures (FS), or febrile convulsions (FEB), are acute symptomatic seizures that occur in response to fever and represent the most common form of childhood seizures. Generalized epilepsy with febrile seizures plus (GEFS+) is a familial epilepsy syndrome with a spectrum of phenotypes including FS. Severe epilepsy phenotypes such as Dravet syndrome (SMEI) have also been described within GEFS+ families. A significant genetic component exists for susceptibility to FS and GEFS+. Extensive genetic studies have shown that at least ten loci are responsible for FS. Furthermore, mutations in the voltage-gated sodium channel subunit genes (SCN1A, SCN2A and SCN1B) and the GABA(A) receptor subunit genes (GABRG2 and GABRD) have been identified in GEFS+.","Nervous system disease"
"H02488","Cardiac-urogenital syndrome","Cardiac-urogenital syndrome (CUGS) is characterized by congenital diaphragmatic hernia, congenital heart disease and genitourinary abnormalities. Mutations in MYRF have been identified in patients. MYRF is a membrane-associated transcription factor that plays a pivotal role in oligodendrocyte differentiation and myelination.","Congenital malformation"
"H01803","Pulmonary atresia with ventricular septal defect","Pulmonary atresia with ventricular septal defect (PA-VSD) is a rare and complex cyanotic congenital heart malformation that has a high incidence of early mortality. PA-VSD presents with complete absence of any communication between the right ventricle and the pulmonary arteries. The blood supply to the pulmonary arteries is provided by a patent arterial duct or by major aorto pulmonary collateral arteries (MAPCAs). Two-thirds of the cases with pulmonary atresia are associated with MAPCAs, which can vary greatly in number and site of origin. PA-VSD shares similarities with tetralogy of Fallot (TOF) and has been considered a severe end of the spectrum of TOF. Although surgical interventions have been employed successfully for a number of years, the long-term prognosis has remained poor with an increased incidence of sudden death. An association between conotruncal cardiac abnormalities and 22q11.2 deletion during fetal life has been investigated and reported to occur in 20% of cases of PA-VSD.","Developmental disorder; Cardiovascular disease"
"H00589","Familial exudative vitreoretinopathy","Familial exudative vitreoretinopathy (FEVR) is inherited retinal disorders with ocular manifestations that are caused by alterations in the Wnt signaling network. FEVR has an abnormal vascularization of the peripheral retina with the formation of retinal folds, retinal detachment, and in many cases the creation of a fibrovascular membrane located behind the lens. Mutations in NDP, FZD4, and LRP5 have been reported to be responsible for ophthalmic diseases including Norrie disease, FEVR, and osteoporosis pseudoglioma syndrome. The proteins encoded by these genes have all been shown to participate in the Wnt/Norrin signaling pathway. Recently, heterozygous mutations in TSPAN12, which is a component of the Norrin-FZD4-LRP5 signaling complex, have been found to be responsible for autosomal dominant FEVR.","Nervous system disease"
"H01669","Secondary hyperparathyroidism","Secondary hyperparathyroidism (SHPT) is a chronic and progressive disorder characterized by elevated serum parathyroid hormone (PTH), parathyroid gland hyperplasia, and disturbances in mineral metabolism, mainly calcium and phosphorus. SHPT is generally caused by diffuse parathyroid hyperplasia in response to prolonged reduced levels of extracellular calcium from various secondary aetiologies. Although it is initially and adaptive response to a variety of stimuli resulting mainly in extracellular hypocalcaemia (vitamin D deficiency, chronic kidney disease, idiopathic hypercalciuria, calcium malabsorption), long-standing SHPT may eventually develop into autonomous HPT (ie, tertiary HPT). Because SHPT is a compensatory mechanism of the parathyroid glands, it commonly resolves with normalization of calcium and phosphorus homeostasis. After excluding reversible secondary aetiologies, first-line treatment of irreversible SHPT (often related to chronic kidney disease) mainly involves medical therapies.","Endocrine disease"
"H02018","Central precocious puberty","Central precocious puberty is caused by early maturation of the hypothalamic-pituitary-gonadal axis. Recently, kisspeptin receptor (KISS1R) and its ligand, kisspeptin, were described as an excitatory neuroregulator system for the secretion of gonadotropin-releasing hormone (GnRH). Mutations of the KISS1R gene were identified in patients with impaired pubertal development. It has also been reported that central precocious puberty caused by mutations in the imprinted gene MKRN3.","Endocrine disease"
"H00925","2-Methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) deficiency","2-Methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) deficiency is a recently described X-linked inborn error in the metabolism of isoleucine. MHBD is characterized by normal early development followed by progressive loss of mental and motor skills.","Inherited metabolic disease"
"H00119","Congenital disorders of glycosylation type II","Congenital disorders of glycosylation (CDG) are a group of disorders caused by defects in various genes for N-glycan biosynthesis. CDG-II is defined by mutations in genes encoding enzymes in the processing of N-glycans on the glycosylated proteins either late in the endoplasmic reticulum or the Golgi compartments. Multiple subtypes have been identified although the numbers and forms of affected individuals with CDG-I are still much more. In contrast to type I, the type II patients show a more severe psychomotor retardation, no peripheral neuropathy and a cerebellar hypoplasia. According to the serum transferrin glycoform, a portion of CDG-II can be diagnosed. Distinct from CDG-I, the serum trisialo- and asialotransferrin are increased in CDG-II.","Inherited metabolic disease"
"H01656","Psoriasis","Psoriasis (PSORS) is a chronic, immune-mediated inflammatory skin disease, characterized by increased propagation of the epidermis with dilation of dermal capillaries. The major symptoms of psoriasis are itchy, scaly, and flaky skin, swelling, pain, and disfiguring skin lesions. Plaque psoriasis is the most common form. Other forms include flexural, guttate, nail, inverse psoriasis, erythroderma, and psoriatic arthritis. Nail psoriasis can accompany any form of psoriasis or occur of its own accord. It can occur in any age group, but psoriatic arthritis usually develops between the ages of 30-50 years. Various factors such as bacterial infection, genetic and environmental factors, and immune disorders play an important role in causing psoriasis. Psoriasis is associated with several comorbidities, including cardiovascular disease, lymphoma, and depression. Psoriasis is an immune-mediated disease with genetic predisposition, but no distinct immunogen has been identified. The presence of cytokines, dendritic cells, and T lymphocytes in psoriatic lesions has prompted the development of biologic therapies. The diagnosis is usually clinical, based on the presence of typical erythematous scaly patches, papules, and plaques that are often pruritic and sometimes painful. Biopsy is rarely needed to confirm the diagnosis. First-line therapies for most patients are topical treatments such as topical corticosteroids and vitamin D analogs. For those with more severe or treatment-resistant disease, second- or third-line therapies include phototherapy, systemic therapies such as methotrexate, and more recently biologic therapies such as tumour necrosis factor (TNF) inhibitors.","Skin and connective tissue disease; Immune system disease"
"H00784","Localized autosomal recessive hypotrichosis","Localized autosomal recessive hypotrichosis (LAH) is a rare non-syndromic human alopecia/hypotrichosis that is inherited as an autosomal recessive trait. Affected individuals display short, sparse hairs on the scalp, trunk, and extremities. Facial hair including the eye-brows, eye-lashes and beard show a broad range of hypotrichosis from almost normal to less dense condition. Patients' skin is normal.","Skin disease"
"H01464","Mantle cell lymphoma","Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma (NHL) and it accounts for about 6% of all NHL cases. Diagnosis is based on lymph node, bone marrow, or tissue morphology of centrocytic lymphocytes, small cell type, or blastoid variant cells. The molecular hallmark and putative initiating oncogenic event in MCL is the t(11;14)(q13;q32) translocation resulting in constitutional overexpression of cyclin D1 and cell cycle dysregulation in almost all cases. Clinically, MCL shows an aggressive clinical course with a continuous relapse pattern and a median survival of only 3-5 years. However, recently a subset of 15% long-term survivors has been identified with a rather indolent clinical course.","Cancer"
"H01000","Retinal vasculopathy with cerebral leukodystrophy","Retinal vasculopathy with cerebral leukodystrophy (RVCL) is a rare autosomal dominant microvascular endotheliopathy with middle-age onset. At around the age of 45, affected individuals may develop retinal and cerebral dysfunction. Death occurs in most cases within 10 years of the first symptoms appearing. The disease-causing mutations of TREX1 lead to truncation and abnormal localization of the 3'-5' exonuclease.","Nervous system disease"
"H01232","Syndromic multisystem autoimmune disease","Syndromic multisystem autoimmune disease is characterized by organomegaly, failure to thrive, developmental delay, dysmorphic features and autoimmune inflammatory cell infiltration of the lungs, liver and gut. It has been reported that human ITCH E3 ubiquitin ligase deficiency causes this disease.","Immune system disease"
"H00126","Gaucher disease","Gaucher disease is an autosomal recessive lysosomal storage disorder caused by deficient beta-glucocerebrosidase (glucosylceramidase) activity or saposin C which is an activator of beta-glucocerebrosidase in sphingolipid metabolism. The enzymatic defects lead to the accumulation of glucosylceramide (GC) in lysosomes of affected cells. Despite the fact that Gaucher Disease consists of a phenotype, with varying degrees of severity, it has been sub-divided in three subtypes according to the presence or absence of neurological involvement. The sub-types are Type 1, 2 and 3.","Inherited metabolic disease; Lysosomal storage disease; Nervous system disease"
"H00314","Meningococcal infection","Neisseria meningitidis is a gram-negative bacterial pathogen that specifically infects humans. It is a frequent asymptomatic colonizer of the human upper respiratory tract, and most adults are resistant to infection through acquired immunity. In susceptible individuals, it causes meningococcal meningitis and severe septicemia.","Infectious disease"
"H02027","Male hypogonadism","Hypogonadism in male patients is characterized by a deficiency in testosterone - a critical hormone for sexual, cognitive, and body function and development. Low testosterone levels may be due to testicular, hypothalamic, or pituitary abnormalities.","Endocrine disease; Reproductive system disease"
"H00770","Congenital myasthenic syndrome","Congenital myasthenic syndromes (CMS) are a heterogenous group of genetic disorders caused by mutations in several proteins that compose the neuromuscular junction (NMJ) apparatus on which synaptic formation and function depend. The majority are recessively inherited. The disorders of the NMJ cause weakness and fatigue.","Nervous system disease"
"H01490","Multiple sclerosis","Multiple Sclerosis (MS) is a chronic disease of the central nervous system (CNS) characterized by inflammation, demyelination and axonal loss. This disease typically strikes young adults, especially women. There are four types of MS according to their relapsing or progressive pattern that include relapsing-remitting (RRMS), secondary progressive (SPMS), primary progressive (PPMS), and progressive relapsing (PRMS). In most patients, the disease has a relapsing-remitting course during the first years. Within 10 years, approximately 50% of patients progress to SPMS. The aetiology of MS is not well understood, but it is likely multifactorial, combining both genetic and environmental factors. Recently, the literature on the risk factors for MS has grown substantially. They indicate that a combination of a genetic predisposition, exposure to Epstein-Barr virus, cigarette smoking, and reduced sunlight exposure/vitamin D levels is involved. Authorized first-line treatments are considered equally effective, and include interferon beta and glatiramer acetate. They are primarily directed against inflammation, and might fail to adequately control disease activity in some patients. In that case, it has been recommended to switch these patients early to a therapy of higher efficacy. Currently, 13 different drugs with ten different active components are licensed in the European Union (EU) and the United States (US) for the treatment of MS.","Nervous system disease"
"H00542","Polycystic kidney disease","Polycystic kidney disease (PKD) is the most common life-threatening genetic disease characterized by bilateral cyst formation on the kidneys. It is often associated with liver cysts.","Congenital malformation"
"H02215","Childhood absence epilepsy","Childhood absence epilepsy (CAE/ECA) is a common idiopathic generalized epilepsy, accounts for 10% to 12% of epilepsy in children under 16 years of age. This condition begins in childhood with absences, which are brief episodes of loss of consciousness. It has been reported that mutations in several genes encoding subunits of the GABAA receptor are associated with this disease.","Nervous system disease"
"H01430","Viral gastroenteritis","Viral gastroenteritis is an infection of the stomach and intestines caused by a variety of viruses. Rotavirus, enteric adenovirus, calicivirus, and astrovirus typically cause diarrhea in infants and young children, whereas the Norwalk group of viruses (and occasionally calicivirus and astrovirus) produces explosive epidemics of gastroenteritis associated with contaminated water and foods, in adults as well as school-age children. No effective treatments have been developed for viral gastroenteritis. Current efforts are targeted at the development of suitable vaccines and the implementation of infection control measures.","Infectious disease"
"H01602","Gastroesophageal reflux disease","Gastro-oesophageal reflux disease (GERD) is a condition in which reflux of the stomach contents into the oesophagus results in symptoms or, occasionally, complications. GERD can be classified as non-erosive reflux disease (NERD) or erosive reflux disease (ERD) based on the presence or absence of esophageal mucosal damage seen on endoscopy. ERD can manifest in a wide range of symptoms which can be subdivided into typical, atypical, and extraesophageal symptoms. Typical symptoms include heartburn and acid regurgitation which have high specificity but low sensitivity for GERD. Atypical symptoms such as epigastric pain, dyspepsia, nausea, bloating, and belching may be suggestive of GERD but may overlap with other conditions in the differential diagnosis. Lastly, there are various extraesophageal symptoms including chronic cough, asthma, laryngitis, and dental erosions. In a small but important minority, complications of peptic oesophagitis may occur including oesophageal strictures, Barrett's oesophagus, and rarely oesophageal adenocarcinoma. Hiatus hernia is statistically associated with GERD, the presence of which is relevant to surgical treatment. The diagnosis is typically made by a combination of clinical symptoms, response to acid suppression, as well as objective testing with upper endoscopy and esophageal pH monitoring. GERD is a chronic disease that typically requires long term management in the form of lifestyle modification, medical therapy and, for a subset of patients, surgical therapy. The mainstay of treatment is acid suppression which can be achieved with several classes of medications including antacids, histamine-receptor antagonists (H2RAs), or proton-pump inhibitors (PPIs).","Digestive system disease"
"H02087","Vertebral, cardiac, renal, and limb defects syndrome","Vertebral, cardiac, renal, and limb defects syndrome (VCRL) is an autosomal recessive congenital malformation syndrome. It has been reported that disruption of nicotinamide adenine dinucleotide (NAD) synthesis causes a deficiency of NAD and congenital malformations in humans and mice.","Congenital disorder of metabolism"
"H01266","Hypercarotenemia and vitamin A deficiency","Hypercarotenemia and vitamin A deficiency is caused by mutation in the CMO1(BCMO1) gene, that catalyzes the first step in the conversion of dietary provitamin A carotenoids to vitamin A. Vitamin A is essential for normal embryonic development as well as normal physiological functions.","Inherited metabolic disease"
"H00186","Hyperargininemia","Hyperargininemia is an autosomal recessive disorder caused by a defect in the arginase I enzyme resulting in high plasma arginine and ammonia levels, that develops encephalopathy.","Inherited metabolic disease; Nervous system disease"
"H01054","Pediculosis","Pediculosis is the result of infestation by Pediculus humanus capitis (head louse)  and Pediculus humanus corporis (body louse), sucking lice belonging to the family Pediculidae. Head louse is transmitted by close contact or by fomites such as combs. Transmission of body louse occurs mainly through contact with contaminated clothing or bedding. Body louse is major vectors of diseases such as epidemic typhus [DS:H00322], trench fever [DS:H00327], and relapsing fever [DS:H00427].","Infectious disease"
"H01868","Mitral valve prolapse","Mitral valve prolapse (MVP) is a very common clinical condition that refers to a systolic billowing of one or both mitral valve leaflets into the left atrium. MVP can be associated with significant mitral regurgitation (MR), bacterial endocarditis, congestive heart failure, and even sudden death. According to the presently used echocardiographic criteria, MVP is defined as an upward displacement of the mitral leaflets that exceeds 2 mm during diastole. In classical MVP, the leaflets' maximal thickness is >5 mm, whereas in non-classical MVP it remains <5 mm. MVP may or may not have associated mitral regurgitation. MVP can be distinguished into primary or nonsyndromic MVP and secondary or syndromic MVP. In the latter case, MVP occurs in the presence of connective tissue disorders such as Marfan syndrome (MFS) [DS:H00653], Loeys-Dietz syndrome [DS:H00800], Ehlers-Danlos syndrome [DS:H00802], and osteogenesis imperfecta [DS:H00506]. Nonsyndromic MVP can be sporadic or familial, demonstrating autosomal dominant and X-linked inheritance. Three different loci on chromosomes 16, 11 and 13 have been found to be linked to MVP. Another locus on chromosome X has been found to cosegregate with a rare form of MVP called X-linked myxomatous valvular dystrophy.","Cardiovascular disease"
"H00340","Vancomycin-resistant enterococci infection","Enterococci are gram-positive, facultative bacteria with low intrinsic virulence that constitute the normal colonizing flora of the human gastrointestinal tract. Vancomycin-resistant enterococci (VRE) are among the most common antimicrobial-resistant pathogens globally, causing bacteremia with or without endocarditis, and intra-abdominal, wound, and genitourinary infection in immunocompromised patients. The mortality rate is high.","Infectious disease"
"H01292","Nance-Horan syndrome","Nance-Horan syndrome (NHS) is an X-linked developmental disorder characterized by congenital cataract, dental anomalies, facial dysmorphism and, in some cases, mental retardation. Mutations in NHS gene have been identified in patients with this syndrome.","Congenital malformation"
"H02417","Gingival fibromatosis with hypertrichosis","Gingival fibromatosis with hypertrichosis is a rare autosomal recessive congenital generalized hypertrichosis terminalis. It is characterized by hair growth that is excessive for the body size and age of an individual and is independent of androgen stimulation. It has been reported that mutations in the cholesterol transporter gene ABCA5 are associated with this disease.","Congenital malformation"
"H00172","Maple syrup urine disease","Maple syrup urine disease (MSUD) is an autosomal recessive inherited disorder caused by a defect in the oxidative decarboxylation of branched-chain amino acids (BCAA) leading to mental and physical retardation, feeding problems, and a maple syrup odor to the urine. Currently, there are effective therapies that are in use for MSUD; the dietary therapy and thiamin supplementation. The dietary therapy, which involves feeding patients with a synthetic diet containing reduced BCAA contents.","Inherited metabolic disease; Nervous system disease"
"H02241","Ehlers-Danlos syndrome cardiac valvular type","Ehlers-Danlos syndrome cardiac valvular type (EDSCV) is a rare autosomal recessive form of EDS. In addition to the usual skin and joint involvement, patients appear to be at increased risk for cardiac valvular dysfunction. Mutations in the COL1A2 gene that encodes type I collagen can give rise to EDSCV.","Congenital malformation"
"H00516","Cleft lip and/or cleft palate","Cleft lip and/or cleft palate (orofacial cleft, OFC) represents a spectrum of craniofacial anomalies. These clefts are one of the most common congenital malformations that can arise as part of a syndrome or in the absence of other defects. A large fraction of clefts occurs without other defects and is termed isolated orofacial clefts.","Congenital malformation"
"H00724","White sponge nevus","White sponge nevus is a benign autosomal dominant disorder affecting non-cornifying stratified squamous epithelia with white spongy plaques in the mouth. Mutations in KRT4 and KRT13, which are expressed in the mucosal non-cornifying stratified epithelia, are associated the disease.","Congenital malformation"
"H02073","Wagner syndrome","Wagner syndrome is a rare dominantly inherited vitreoretinopathy, characterized by an optically empty vitreous with avascular vitreous strands and veils. Wagner syndrome is caused by mutations in VCAN, encoding a chondroitin sulfate proteoglycan termed versican.","Nervous system disease"
"H00985","Bare lymphocyte syndrome type2","Bare lymphocyte syndrome (BLS) is a rare recessive genetic immune disorder endorsed by a partial or complete absence of major histocompatibility complex (MHC) or human leukocyte antigen (HLA) expression. BLS could be grouped as type I, type II, and type III based on defective surface MHC expression. A feature of loss in constitutive and inducible MHC II proteins have been grouped as BLS type II. The abnormality of the transcription factors, which combine to form a singular transcription complex essential for the initiation of the transcription of MHC II, contributes to the development of BLS type II. BLS type III is recognized by the loss of both MHC I and MHC II molecules.","Inherited metabolic disease; Immune system disease"
"H01857","Filippi syndrome","Filippi syndrome is a rare autosomal-recessive disorder characterized by mild to severe mental retardation, syndactyly of the fingers and toes, microcephaly, pre and postnatal growth retardation, and unusual facies. Syndactyly of hands and feet seems to be the hallmark of the syndrome; 3-4 finger syndactyly being the most common. The facial appearance, including prominent nasal bridge with hypoplastic alae nasi, is similar in all patients. It has been shown that loss-of-function mutations in CKAP2L are a major cause of Filippi syndrome.","Congenital malformation"
"H01259","Giant axonal neuropathy","Giant axonal neuropathy is a disorder that shows giant axons, caused by accumulation of neurofilaments. Giant axonal neuropathy 1 (GAN1) is autosomal recessively inherited and caused by mutations in GAN (gigaxonin). GAN1 is characterized by an early onset severe peripheral neuropathy, varying central nervous system involvement and strikingly frizzly hair. Giant axonal neuropathy-2 (GAN2) is an autosomal dominant disorder, caused by mutations in DCAF8. GAN2 is characterized by distal sensory impairment and lower extremity muscle weakness and atrophy after the second decade.","Neurodegenerative disease"
"H00529","Cranioectodermal dysplasia","Cranioectodermal dysplasia (CED) is a rare disorder characterized by defects of ectoderm-derived structures with typical craniofacial appearances, skeletal deformities and tubulointerstitial nephritis. The craniofacial features include dolichocephaly, sagittal craniosynostosis, and hypoodontia.","Congenital malformation"
"H00971","Achromatopsia","Achromatopsia (Rod monochromacy/ACHM) is an autosomal recessive retinal dystrophy with a prevalence of 1 in 33,000 individuals. It is characterized by low visual aquity, photophobia, nystagmus, difficulty in color discrimination, and no recordable cone function in electroretinography with normal rod functions. The condition is caused by genetic defects affecting crucial components of the cone photoreceptor signaling.","Nervous system disease"
"H02428","Trichosporonosis","Trichosporonosis is a rare mycosis caused by various species in the Trichosporon genus. The first description of clinical isolates of Trichosporon spp. was in 1867. This yeast-like pathogen may cause deep-seated, mucosa-associated, or superficial infections. Invasive trichosporonosis is documented mostly in patients with hematological malignancies and other medical conditions associated with immunosuppression. The most common species are Trichosporon cutaneum and T. asahii.","Infectious disease"
"H00723","Non-epidermolytic palmoplantar keratoderma","Nonepidermolytic palmoplantar keratoderma (NEPPK) is an autosomal dominant skin disorder that manifests as keratosis of the palmar and plantar surfaces surrounded by erythema. NEPPK is divided into the focal form (FNEPPK), the focal or diffuse form (PPKNEFD), the diffuse Bothnian form (PPKB), Nagashima form (PPKN), and so on.","Congenital malformation"
"H02074","Knobloch syndrome","Knobloch syndrome (KNO) is an autosomal recessive disorder characterized by the early onset of severe myopia, vitreoretinal degeneration with retinal detachment, and occipital encephalocele. Mutations in the COL18A1 gene were identified in KNO families.","Congenital malformation"
"H02246","Ehlers-Danlos syndrome musculocontractural type","Ehlers-Danlos syndrome musculocontractural type (EDSMC) is an autosomal recessive disorder characterized by connective tissue fragility, craniofacial abnormalities, congenital contractures, and developmental anomalies. EDSMC is caused by mutations in CHST14, encoding dermatan 4-O-sulfotransferase-1 (D4ST1). Recently, mutations in DSE, encoding dermatan sulfate epimerase-1, have been identified in a child with EDSMC features.","Congenital malformation"
"H00511","Short rib-polydactyly syndrome","Short-rib polydactyly syndromes (SRPS) are most frequent autosomal recessive osteochondrodysplasias ascribed to mutations in DYNC2H1, a cytoplasmic dynein. The fetus with SRP develops polydactyly, shortened tubular bones, and other malformations such as cleft lip/palate.","Congenital malformation"
"H00175","Propionic acidemia","Propionic acidaemia is caused by a deficiency of propionyl-CoA carboxylase which accumulates toxic compounds affecting brain metabolism.","Inherited metabolic disease; Hematologic disease"
"H00949","Focal dermal hypoplasia","Focal dermal hypoplasia, also known as Goltz-Gorlin syndrome, is a rare X-linked dominant disorder characterized by patchy dermal hypoplasia and fat herniation through skin in combination with skeletal, ocular and dental abnormalities. Skeletal dysplasia consisting of syndactyly, polydactyly, camptodactyly or ectrodactyly and ocular anomalies such as colobomas, microphthalmia or cataract are frequently reported. Mutations in the PORCN gene has been shown to cause the disease.","Congenital malformation"
"H00347","Chlamydia infection","Chlamydia trachomatis is a gram-negative, obligate intracellular bacterium that causes the most common sexually transmissible diseases in the world. Chlamydial infection can cause cervicitis in women and urethritis in men. Most of these infections are asymptomatic but, if not treated, can lead to non-gonococcal urethritis and post-gonococcal urethritis in men. Urethritis can be complicated by acute epididymitis.","Infectious disease"
"H01295","Neurodegeneration due to cerebral folate transport deficiency","Neurodegeneration due to cerebral folate transport deficiency is an autosomal recessive disorder of brain specific folate deficiency, characterized by severe developmental regression, movement disturbances, epilepsy, and leukodystrophy. Folate-receptor alpha (FOLR1) is of central importance for folate transport across the blood brain barrier via the choroid plexus. It has been reported that mutations in FOLR1 cause this disease. Folinic acid therapy can reverse the clinical symptoms and improve brain abnormalities and function.","Neurodegenerative disease"
"H02410","Myelodysplastic/myeloproliferative neoplasms","Myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are hybrid group of chronic myeloid neoplasms combining features of both myelodysplastic (MDS) [DS:H01481] and myeloproliferative neoplasms (MPN). This group includes chronic myelomonocytic leukemia (CMML), its pediatric counterpart juvenile myelomonocytic leukemia (JMML), MDS/MPN with ringed sideroblasts and thrombocytosis (MDS/MPN-RS-T), atypical BCR-ABL1 negative chronic myeloid leukemia (aCML) and MDS/MPN- unclassifiable (MDS/MPN-u). Somatic mutations observed in MDS/MPN fall in 4 major categories, including signaling, splicing, epigenetic, and transcription gene mutations.","Cancer"
"H00181","3-Methylcrotonylglycinuria","3-Methylcrotonyl-CoA carboxylase (MCC) deficiency is an autosomal recessive disorder of leucine catabolism with a variable phenotype.","Inherited metabolic disease"
"H01053","Paroxysmal nocturnal hemoglobinuria","Paroxysmal nocturnal hemoglobinuria (PNH) is an uncommon intravascular hemolytic anemia that results from the clonal expansion of hematopoietic stem cells harboring somatic mutations in an X-linked gene, termed PIG-A. PIG-A is required for the biosynthesis of a lipid moiety, glycosylphosphatidylinositol (GPI), that attaches dozens of different proteins to the cell surface. PIG-A mutations block GPI anchor biosynthesis, resulting in a deficiency or absence of all GPI-anchored proteins on the cell surface. This deficiency on erythrocytes leads to intravascular hemolysis since certain GPI anchored proteins normally function as complement regulators.","Hematologic disease"
"H01261","Congenital glucose-galactose malabsorption","Glucose-galactose malabsorption (GGM) is an autosomal recessive disorder that is due to mutations in the gene coding for the sodium-glucose cotransporter (SGLT1/SLC5A1). GGM is characterized by neonatal onset of watery and acidic diarrhea, which becomes fatal within a few weeks unless glucose and galactose containing nutrients are removed from the diet.","Inherited metabolic disease"
"H01605","Myelofibrosis","Myelofibrosis (MF), one of the three classic Philadelphia-chromosome-negative myeloproliferative neoplasms (MPNs), is characterized by symptoms mainly derived from anemia and splenomegaly and constitutional symptoms and associated with a median survival around 6 years. Most MPN patients harbor an acquired mutation in the hemopoietic cells, the V617F mutation, located in the pseudokinase domain of the JAK2 gene. This mutation results in a gain of function, i.e., in the constitutive activation of the JAK-STAT pathway, which plays an important role in the proliferation, differentiation, and survival of the hemopoietic cells, as well as in the immune function. Besides, a minority of patients with MF (most of them negative for the JAK2 mutation) harbor other JAK-STAT-activating mutation, the MPL mutation, in the gene of the receptor of the thrombopoietin. Recently, mutations in the CALR gene have been described in 86% of cases with primary MF that are negative for JAK2 or MPL mutations. CALR mutation also showed cytokine independent growth of cells due to activation of STAT5 involved with the JAK-STAT pathway but its exact role in MPN remains to be clarified.","Cancer"
"H02080","Fibrochondrogenesis","Fibrochondrogenesis is a very rare, neonatally lethal, short-limb skeletal dysplasia. It is an autosomal recessive disorder shown to result from mutations in the COL11A1 type XI collagen gene. Recently, It has been demonstrated that fibrochondrogenesis can result from either recessively or dominantly inherited mutations in COL11A2.","Congenital malformation"
"H01437","Neurofibromatosis type 1","Neurofibromatosis type 1 (NF1), also known as von Recklinghausen's disease, is an autosomal dominant disease caused by mutations of NF1 gene on chromosome 17. The NF1 gene encodes a RAS GTPase-activating protein called neurofibromin. It is one of the most frequent human genetic diseases, with a prevalence of one case in 3000 births and there is no sex or racial predilection. NF1 is characterized by multiple cafe-au-lait spots, axillary and inguinal freckling, multiple cutaneous neurofibromas, and iris Lisch nodules. Learning disabilities are present in at least 50% of individuals with NF1. Less common but potentially more serious manifestations include plexiform neurofibromas, optic nerve and other central nervous system gliomas, malignant peripheral nerve sheath tumors, scoliosis, tibial dysplasia, and vasculopathy.","Congenital malformation"
"H00378","Lyssavirus infection","Lyssaviruses belong to the genus Lyssavirus, within the family Rhabdoviridae and the order Mononegavirales of -ssRNA viruses. The genus Lyssavirus currently includes rabies virus [DS:H00377] and 6 rabies-related viruses. Rabies-related lyssaviruses utilize mostly bats as their principal reservoir hosts as well as various terrestrial carnivores as terminal hosts. They can cause acute, fatal encephalitis similar to that seen with rabies virus infection of humans. There is no effective treatment.","Infectious disease"
"H01098","Pentastomiasis","Pentastomiasis is an unusual parasitic zoonosis caused by the larval stages of pentastomes (tongue worms), generally limited to the tropics and subtropical areas. Its definitive hosts are reptiles whilst humans serve as rare intermediate hosts. Infection is usually asymptomatic.","Infectious disease"
"H00976","Colorblindness","Colorblindness is the inability or decreased ability to perceive color differences. Dichromacy is a condition characterized by reduced dimension of color vision in which one of the three basic color mechanisms is absent or not functioning. Anomalous trichromacy is the milder form of color vision deficiency, with ability to discriminate between different colors in varying degrees but not normal. Dichromacy and anomalous trichromacy are subdivided into three types: protan, deutan, and tritan depending on the affected cone type. Protan and deuten types consist red-green defects. Inherited red-green color vision defects affect 8% of males. Tritan type defect leads to inherited blue-yellow defect that is fairly rare.","Nervous system disease"
"H02279","Cathepsin D deficiency","Cathepsin D deficiency underlies congenital neuronal ceroid-lipofuscinosis (NCL). It represents the earliest-onset and the most aggressive form of the NCL, leading to extreme brain atrophy and death soon after birth. Cathepsin D is a lysosomal protein encoded by the CTSD gene. Recently, novel mutations in CTSD with a juvenile onset of NCL has been reported.","Congenital disorder of metabolism"
"H01408","Periodontal disease","During the early stages of the periodontal disease, saccharolytic, aerobic Streptococcus spp. and other bacteria adhere to and colonize the tooth enamel and root surface. This sets the stage for Fusobacterium nucleatum to coaggregate with these early colonizers and to permit late colonizers, including dental pathogens, to eventually form a biofilm. These complex interactions result in the release of factors that lead to tooth decay. Physical interaction is very specific among various genera in this complex microbial community. Due to the unusual length, adhesive nature, and other cell surface properties of F. nucleatum, periodontal disease-causing bacteria such as Porphyromonas gingivalis, Bacteroides forsythus, Aggregatibacter actinomycetemcomitans, Treponema denticola, and Streptococcus spp. aggregate and thrive; hence, F. nucleatum is thought of as a 'bridge bacterium'.","Infectious disease"
"H00982","Sideroblastic anemia","Sideroblastic anemias are a group of disorders characterized by anemia with the emergence of ring sideroblasts in the bone marrow. Inherited sideroblastic anemia is a rare and heterogeneous disease caused by mutations of genes involved in heme biosynthesis, iron-sulfur cluster biogenesis or transport, and mitochondrial metabolism.","Hematologic disease"
"H01850","Hartsfield syndrome","Harstfield syndrome is the rare and unique association of holoprosencephaly (HPE) and ectrodactyly, with or without cleft lip and palate, and variable additional features. HPE and ectrodactyly can occur, separately, as part of numerous syndromes, but the co-occurrence of these two malformations has only been reported only in a very limited number. Additional signs such as craniosynostosis, hypertelorism or hypotelorism, microphthalmia, abnormal ears, radial agenesis, genital anomalies, severe psychomotor retardation, and hypothalamic-pituitary dysfunction have been observed. Dominant or recessive FGFR1 mutations are responsible for Hartsfield syndrome.","Congenital malformation"
"H01091","Enterobiasis","Enterobiasis is one of the most widespread parasitic nematode infections caused by Enterobius vermicularis that commonly referred to as pinworm. This infection is usually associated with pruritis in the perianal region.","Infectious disease"
"H00143","Mucolipidosis II","Mucolipidosis type II, also known as I-cell disease, autosomal recessive lysosomal storage disorders caused by the deficiency of N-acetylglucosamine-1-phosphate transferase which is multimeric enzyme involved in phosphotransfer of UDP-N-acetylglucosamine to lysosomal enzymes (glycoproteins). It is the necessary process for the transport of newly synthesized lysosomal proteins to the lysosomes.","Congenital disorder of metabolism"
"H02426","EDICT syndrome","EDICT syndrome is an autosomal dominant syndrome characterized by endothelial dystrophy, iris hypoplasia, congenital cataract, and stromal thinning. It has been reported that a single-base substitution in the seed region of miR-184 causes EDICT syndrome.","Congenital malformation"
"H00371","Adenovirus infection","Adenoviruses (Ads) are recognized as etiologic agents of the respiratory and gastrointestinal tracts, eye, and kidney. Ads are rarely associated with severe clinical symptoms in healthy individuals. In contrast, in the pediatric population, military recruits, and immunocompromised individuals, Ad infections often result in disseminated and potentially life-threatening disease. Ocular Ad infections are among the leading causes of viral conjunctivitis.","Infectious disease"
"H02042","Familial expansile osteolysis","Familial expansile osteolysis (FEO) is a rare autosomal dominant disorder causing bone dysplasia. It is characterized by increased osteoclast activity, medullary expansion, and hearing and dental problems. The mutations in the TNFRSF11A gene encoding RANK have been identified. FEO is similar in some respects to Paget's disease but distinct enough in its clinical, radiological and histological findings to be classified as a separate disease.","Musculoskeletal disease"
"H00715","Darier disease","Darier disease is a skin disorder with keratotic papules and plaques in seborrheic areas (central trunk, flexures, scalp, and forehead) and nail abnormalities. The disease usually starts at puberty and characterized by loss of cell-to-cell adhesion and abnormal keratinization. Darier disease is caused by mutations in ATP2A2, the gene encoding a sarco/endoplasmic reticulum Ca2+-ATPase. Because of some similarities in their etiopathology, Hailey-Hailey disease [DS:H00844] is often discussed together with Darier disease. Both diseases are autosomal dominantly inherited genodermatosis and are caused by abnormal epidermal calcium homeostasis.","Congenital malformation"
"H00527","Retinitis pigmentosa","Retinitis pigmentosa (RP) is a group of inherited progressive retinal diseases characterized by progressive peripheral vision loss and night vision difficulties. RP can be divided into syndromic (40 %) and non-syndromic (60 %) forms. The most frequent forms of syndromic RP are Usher syndrome and Bardet-Biedl syndrome. Mutations in more than 50 genes are known to cause non-syndromic RP. Non-syndromic RP can be inherited in an autosomal dominant, autosomal recessive, or X-linked manner.","Nervous system disease"
"H02270","Cavitary optic disc anomalies","Congenital cavitary optic disc anomalies (CODA) include optic disc coloboma, morning glory disc anomaly, optic pit, and the papillorenal syndrome. Recently, a copy number variation upstream of matrix metalloproteinase 19 (MMP19) has been discovered in an autosomal dominant pedigree with CODA.","Congenital malformation"
"H01633","High blood pressure","High blood pressure (hypertension) is the most frequent classic cardiovascular risk factor and accounts for a large proportion of cardiovascular mortality, the main cause of death worldwide. Hypertension is generally classified as primary (essential) or secondary. Essential hypertension (EH) is the most common diagnosis in this disease, suggesting that a monocausal etiology has not been identified. However, a number of risk factors associated with EH have also been identified such as age, sex, demographic, environmental, genetic, and vascular factors. Secondary hypertension generally has an earlier age at onset, no family history, and a clear cause such as a renal or endocrine disorder, or an iatrogenic trigger, such as use of oral contraceptives. Blood pressure is a heritable trait; an estimated 30% of variance in blood pressure relates to genetic factors. Understanding of the genetic architecture of traits has progressed in rare mendelian hypertensive phenotypes, such as Gordon's syndrome.","Cardiovascular disease"
"H01401","Methicillin-resistant Staphylococcus epidermidis (MRSE) infection","The genus Staphylococcus known as pathogen of human and other mammals causes various diseases ranging from minor skin infections to life-threatening bacteremia. The two major opportunistic pathogens in the Staphylococcus genus, Staphylococcus aureus and Staphylococcus epidermis, colonize a sizable portion of the human population. S. epidermidis as the predominant species is quite widespread throughout the cutaneous ecosystem, whereas S. aureus colonizes primarily on mucosal surfaces. Staphylococcal infections are commonly caused by S. aureus. However, the infections due to S. epidermidis and other coagulase-negative staphylococci have been also increasing. S. epidermidis is primarily associated with infections of implanted medical devices, such as prosthetic heart valves and joint prostheses.","Infectious disease"
"H02284","Leukotriene C4 synthase deficiency","Leukotriene C4 (LTC4) synthase deficiency is an inborn error of metabolism linked to a fatal developmental syndrome. It is characterised by severe muscular hypotonia, psychomotor retardation, failure to thrive, microcephaly, and the total absence of cysteinyl leukotrienes in body fluids.","Congenital disorder of metabolism"
"H01065","Pentosuria","Pentosuria is an autosomal recessive inherited condition to be inborn errors of metabolism characterized by high levels of the pentose sugar L-xylulose in blood and urine. The condition is completely clinically benign. Mutations have been identified in the DCXR gene encoding L-xylulose reductase, which are predicted to lead to loss of enzyme activity. In pentosuria, failure to convert L-xylulose to xylitol leads to accumulation of L-xylulose.","Urinary system disease"
"H01859","Occipital horn syndrome","Occipital horn syndrome (OHS), formerly known as Ehlers-Danlos syndrome type IX or X-linked cutis laxa, is a mildest form of Menkes disease (MD). MD and OHS are X-linked recessive disorders of impaired copper metabolism due to mutations in the ATP7A gene. The patients with classical MD have severe developmental and neurological impairments due to subnormal amount of copper in the brain and a variety of symptoms such as connective tissue abnormalities, tortuosity of blood vessels and peculiar hair. Most of the classical MD patients die before the age of 3 years. On the other hand, the neurological symptoms of OHS patients are milder and lead to a clinical picture mainly characterized by connective tissue manifestations and skeletal abnormalities that include occipital exostoses, which give rise to the syndrome's name. These patients have normal or close-to-normal cognitive functions.","Inherited metabolic disease; Skin and connective tissue disease"
"H01257","GABA-transaminase deficiency","GABA-transaminase deficiency is a very rare inborn error of GABA degradation. The phenotype of this deficiency includes psychomotor retardation, hypotonia, hyperreflexia, lethargy, refractory seizures, and electroencephalographic abnormalities.","Inherited metabolic disease"
"H00385","South American hemorrhagic fever","Arenaviruses in the genus Mammarenavirus, the family Arenaviridae of -ssRNA viruses have a natural reservoir in rodents and occasionally infect humans causing viral hemorrhagic fevers. Phylogenetically, arenaviruses can be divided into Old World and New World groups, reflecting the restricted geographical distribution of natural reservoir species. This disease category is created in corcondance with the Japanese Infectious Diseases Control Law.","Infectious disease"
"H00518","Metaphyseal dysplasia without hypotrichosis","Metaphyseal dysplasia without hypotrichosis (MDWH) is a skeletal dysplasia, caused by mutations in the RMRP gene. RMRP codes for an RNA subunit of the MRP RNAse complex. Patients have short stature and radiographic changes similar to those of cartilage-hair hypoplasia (CHH), but have normal hair and no immunodeficiency.","Ribosomopathy"
"H02419","Glycine encephalopathy with normal serum glycine","Glycine encephalopathy [DS:H00191], also known as nonketotic hyperglycinemia (NKH), is characterized by severe neurologic dysfunctions. Recently, some individuals with NKH-like symptoms but lacking the typical elevation of serum glycine have been reported. They carry mutations in the SLC6A9 gene, that encodes glycine transporter (GLYT1). GLYT1 is located predominantly on astrocytes and is essential for the clearance of glycine from the extracellular space and termination of glycinergic neurotransmission.","Congenital disorder of metabolism"
"H01892","Peripheral T cell lymphoma","Peripheral T cell lymphomas (PTCLs) are a group of rare lymphomas originating from mature (i.e., post-thymic or 'peripheral') T lymphocytes and NK cells. With regard to the current WHO classification, leukemic, cutaneous, nodal, and extranodal PTCL are distinguished. The most common subtypes worldwide are the nodal T cell lymphomas. In the nodal T cell lymphomas, the major subtypes are PTCL, not otherwise specified (PTCL-NOS), angioimmunoblastic T cell lymphoma (AITL), anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) and ALK-negative ALCL. Novel approaches are gradually clarifying the molecular pathogenesis of PTCLs. ALK gene translocation and dual specificity phosphatase 22 (DUSP22) gene translocation are seen in ALK-positive ALCL and ALK-negative ALCL, respectively. Recently, gene mutations in epigenetic regulators, including Ten-Eleven Translocation 2 (TET2), DNA methyltransferase 3A (DNMT3A), and isocitrate dehydrogenase 1 /2 (IDH1/2), are discovered in hematologic malignancies. The mutation frequencies were especially high in AITL and PTCL-NOS.","Cancer"
"H00940","Cohen syndrome","Cohen syndrome is an autosomal recessive disorder with a broad phenotypic spectrum. Essential symptoms include mental retardation, progressive postnatal microcephaly, typical facial anomalies, ophthalmologic findings such as chorioretinal dystrophy and myopia, and granulocytopenia. Obesity and growth delay could be observed. In most patients, Cohen syndrome is caused by loss-of-function mutations in the COH1 gene.","Congenital malformation"
"H01268","Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome","Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is a rare autosomal recessive disorder, characterized by mental retardation, progressive spastic paraparesis, seizures, and myoclonus epilepsy. This disease varies widely in its severity and age of onset. The HHH syndrome is thought to be caused by the defective activities of the mitochondrial carrier responsible for transporting ornithine from the cytoplasm into the inner mitochondrial membrane. Mutations in the SLC25A15 gene, that encodes the mitochondrial ornithine transporter have been shown to be correlated with the HHH syndrome.","Inherited metabolic disease"
"H00188","Hyperlysinemia","Hyperlysinemia is an autosomal recessive metabolic disorder caused by aminoadipate-semialdehyde synthase deficiency and characterized by an abnormal increase of lysine in the blood.","Inherited metabolic disease; Nervous system disease"
"H01866","Pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis","Pulmonary veno-occlusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH) are rare diseases that are classified as a subgroup of pulmonary arterial hypertension (PAH). PVOD is histologically characterized by intimal fibrosis that narrows and occludes pulmonary veins and it accounts for 5-10% of cases initially thought to be idiopathic PAH (IPAH). PCH is histologically characterized by localized capillary proliferation within the lung in which capillaries invade the pulmonary interstitium, vessels and, less commonly, airways. PCH has been reported to be much less frequent than PVOD. In recent years, PAH-targeted drugs including epoprostenol have improved the survival of patients with IPAH. PVOD/PCH has a very similar clinical presentation to PAH but is characterised by a worse prognosis and the possibility that severe pulmonary oedema can develop with specific PAH therapy. PVOD associated with a BMPR2 mutation has been reported. Recently, it has been suggested that EIF2AK4 mutations are the major cause of heritable PVOD.","Cardiovascular disease"
"H02089","Winchester syndrome","Winchester syndrome is a rare skeletal disorder originally described nearly 50 years ago in two sisters with a severe crippling osteolysis. Previously, Winchester syndrome and multicentric osteolysis, nodulosis, and arthropathy (MONA) [DS:H00472] were presumed to be allelic disorders arising from mutations in the MMP2 gene. But it has been demonstrated that mutations in MMP14 result in this disease.","Musculoskeletal disease"
"H01250","Hereditary gingival fibromatosis","Hereditary gingival fibromatosis (GINGF) is a rare autosomal dominant overgrowth condition characterized by a benign, slowly progressive, nonhemorrhagic, fibrous enlargement of maxillary and mandibular keratinized gingiva. Four gene loci have been mapped for autosomal dominant GINGF. Although the molecular basis of HGF remains largely unknown, a SOS1 gene mutation is identified. Recently, it has been reported that REST final-exon-truncating mutations cause GINGF.","Digestive system disease"
"H00382","Mosquito-borne viral fever","Mosquito-borne viral fevers are infectious diseases caused by arboviruses (arthropod-borne viruses) and transmitted by mosquitoes. Arboviruses are zoonotic viruses and consist of taxonomically different viruses, including flavivirus, alphavirus and bunyavirus.","Infectious disease"
"H01062","Histoplasmosis","Histoplasmosis is a disease caused by the fungus Histoplasma capsulatum that occurs in temperate and tropical climates. It is one of the most frequent invasive fungal infections in immunocompromised patients or patients receiving tumor necrosis factor (TNF) blockers. Most affected patients present with pneumonitis, and sometimes the disease may be disseminated from the lungs to other organs.","Infectious disease"
"H01406","Streptococcus suis infection","Streptococcus suis, a Gram positive coccus, is a zoonotic pathogen that infects pigs and can occasionally cause serious infections in humans. The first case in humans was reported in Denmark in 1968. Human infection with S. suis occurs sporadically in Europe and North-America and case reports suggest that it is almost exclusively related to occupational exposure to pigs or pork products. Incidences of human infection with S. suis are greater in S.E. Asia and China. Meningitis is the most common presentation in humans, but septicaemia and endocarditis are also seen.","Infectious disease"
"H02283","IVIC syndrome","The IVIC syndrome is an autosomal dominant complex pleiotropic syndrome with radial ray hypoplasia, hearing impairment, external ophthalmoplegia, and thrombocytopenia. It is caused by mutations in the SALL4. SALL4 encodes a transcription factor with a wide expression in early embryogenesis, and later expression restricted to adult testis and ovary.","Congenital malformation"
"H01634","Peptic ulcer","Peptic ulcer is a common disorder of gastrointestinal system characterized by mucosal damage secondary to pepsin and gastric acid secretion. It usually occurs in the stomach and proximal duodenum. Typical symptoms include episodic burning epigastric pain, loss of appetite, and weight loss. Pain usually occurs two to five hours after meals or on an empty stomach. The most common causes of peptic ulcer are Helicobacter pylori infection and use of nonsteroidal anti-inflammatory drugs (NSAIDs). Smoking increases the risk of ulcer recurrence and slows healing. Most patients are treated successfully with eradication of H. pylori and/or avoidance of NSAIDs, along with the appropriate use of antisecretory therapy. About 25 percent of patients with peptic ulcer have a serious complication such as hemorrhage, perforation, or gastric outlet obstruction. Administration of proton pump inhibitors (PPIs) and endoscopic therapy control most bleeds.","Digestive system disease"
"H00520","Type II collagenopathies","Type II collagenopathies are a spectrum of phenotypes which affect the skeletal and visual systems. The severity ranges from perinatal lethality (achondrogenesis II) to the milder conditions caused by reduced collagen content in cartilage (Kniest dysplasia).","Congenital malformation"
"H02277","Santavuori-Haltia disease","Santavuori-Haltia disease, also known as the infantile neuronal ceroid lipofuscinosis (INCL), is a rare but one of the most lethal inherited neurodegenerative lysosome storage disorders of childhood. Patients are normal at birth but by 2 years of age they manifest complete retinal blindness and by age four they would be brain-dead. It is caused by inactivating mutations in the palmitoyl-protein thioesterase-1 (PPT1) gene.","Congenital disorder of metabolism"
"H02045","Norrie disease","Norrie disease is a severe X-linked recessive form of congenital blindness, which in about one-half of the cases is accompanied by mental retardation and deafness. Mutations in NDP have been reported.","Congenital malformation"
"H00712","KID/HID syndrome","Keratitis (and hystrix-like) ichthyosis deafness (KID/HID) syndrome is a rare congenital ectodermal dysplasia affecting the skin, hearing and vision. Cutaneous findings include red, thickened plaques with scaling that involve palms and soles. Sensorineural deafness or severe hearing impairment is often congenital. Corneal epithelium may be affected, manifesting as keratitis and photophobia. KID/HID syndrome is an autosomal dominant trait but most cases are sporadic. Recently, autosomal recessive KID syndrome (KIDAR) has been reported. KIDAR is caused by mutations in AP1B1.","Congenital malformation"
"H02421","Solid tumor","Cancers can be classified into two broad types: hematological or solid tumors. There are two main types of solid tumors: carcinomas and sarcomas. Most solid tumors are derived from epithelial cells. Carcinomas are tumors that form in epithelial cells. Neoplastic epithelial cells generate aggressive cancers such as those located in the lung, breast, colon, prostate and ovary. Some cancers of the bladder ureters and kidneys are transitional cell carcinomas. Sarcomas are tumors that start in tissues like a blood vessel, bone, fat tissue, ligament, lymph vessel, muscle or tendon. Examples are given as follows: osteosarcoma, chondrosarcoma, rhabdomyosarcoma, leiomyosarcoma and so on.","Cancer"
"H00376","Acute poliomyelitis","Acute poliomyelitis, often called polio, is an infectious disease caused by any of the three serotypes of poliovirus, an enterovirus in the Picornaviridae family of +ssRNA viruses. Only a small proportion of poliovirus infections results in paralytic poliomyelitis due to the viral invasion to the central nervous system.","Infectious disease"
"H01096","Pyruvate kinase deficiency","Pyruvate kinase (PK) deficiency is inherited metabolic disorder caused by mutations in PKLR that encodes both L-PK (expressed in liver, renal cortex, and small intestine) and R-PK (restricted to erythrocytes). The symptoms include jaundice, enlargement of the spleen, and hemolysis, leading to anemia. One hundred fifty-eight mutations associated with non-spherocytic haemolytic anaemia and eight polymorphic sites have been so far reported in the PKLR gene. It has also been found that a specific mutation in the PKLR gene causes hereditary increase of red blood cell ATP.","Inherited metabolic disease; Hematologic disease"
"H00144","Mucolipidosis IV","Mucolipidosis IV (ML IV) is an autosomal recessive neurodegenerative lysosomal storage disorder characterized by psychomotor retardation and ophthalmologic abnormalities. ML IV is caused by mutations in mucolipin 1 (MCOLN1), a late endosomal/lysosomal ion channel. Cells from patients with MLIV accumulate enlarged vacuolar structures containing phospholipids, sphingolipids, mucopolysaccharides, and gangliosides. Accumulation of lipids results from defects in membrane transport along the late endocytic pathway. It was found that MCOLN1 is required for efficient fusion of both late endosomes and autophagosomes with lysosomes.","Inherited metabolic disease; Nervous system disease; Lysosomal storage disease"
"H00978","Thrombocytopenia (THC)","Thrombocytopenia is defined by a decrease in the number of platelets in circulating blood, resulting in the potential for increased bleeding and decreased ability for clotting. Inherited syndromes are relatively rare causes of thrombocytopenia, but some genes underlying these disorders have been elucidated. Some inherited syndromes predispose to the development of bone marrow failure or leukemia. For example, familial platelet disorder with associated myeloid malignancy (FPDMM) is characterized by qualitative and quantitative platelet defects, and propensity to develop acute myelogenous leukemia.","Hematologic disease"
"H01439","Williams-Beuren syndrome","Williams-Beuren syndrome (WBS) is a rare autosomal dominant multisystem disorder associated with the hemizygous deletion of a number of genes on chromosome 7q11.23. The range of phenotypes may include congenital vascular and heart disease, characteristic facial features, premature aging, generally mild mental retardation, short stature, myopathy, hypercalcemia, and a unique cognitive profile. To date at least 28 genes have been identified within the deleted region.","Chromosomal abnormality"
"H01861","Chromosome 15q24 microdeletion syndrome","Chromosome 15q24 microdeletion syndrome is a rare microdeletion syndrome characterized by growth retardation, intellectual disability, and distinct facial features including long face with high anterior hairline, hypertelorism, epicanthal folds, downslanting palpebral fissures, sparse and broad medial eyebrows, broad and/or depressed nasal bridge, small mouth, long smooth philtrum, and full lower lip. Other common findings include skeletal and digital abnormalities, genital abnormalities in males, hypotonia, behavior problems, recurrent infections, and eye problems. The recurrent deletions of chromosome 15q24 result from non-allelic homologous recombination (NAHR) mediated by low-copy repeat (LCR, also called segmental duplication) clusters. The deletion occurred as a de novo event in all known cases. Recent study has identified that haploinsufficiency of SIN3A (chromosome 15q24.2) is associated with mild syndromic intellectual disability. This phenotype is highly related to that of individuals with atypical 15q24 microdeletions, linking SIN3A to this microdeletion syndrome.","Chromosomal abnormality"
"H01895","Attention deficit hyperactivity disorder (ADHD)","Attention-deficit hyperactivity disorder (ADHD) is a common psychiatric disorder first diagnosed in childhood and frequently persistent throughout adult life. The disorder is classically characterized by symptoms of inattention, impulsivity, and hyperactivity. Many children with ADHD go on to have problems related to education, social functioning, and/or other mental illness as adolescents and young adults. Although heritability estimates are consistently high, ADHD is a genetically complex disorder characterized by multifactorial inheritance involving numerous genes of moderate effect. Reports implicate variants of genes important for the synthesis, uptake, transport and receptor binding of dopamine in the etiology of ADHD. And interaction between the dopamine and serotonin systems has been implicated in both the pathophysiology of ADHD and the mechanism of action of widely used stimulant compounds.","Mental and behavioural disorder"
"H00947","Pilomatricoma","Pilomatricoma is a benign cutaneous tumor of follicular structures. It occurs either in isolation or in conjunction with other symptoms such as myotonic dystrophy and Rubenstein-Taybi syndrome. The histologic appearance of the tumor is characterized by cells resembling those of the hair follicle matrix and sometimes show differentiation toward the follicular infundibulum and surrounding sheath.","Skin and connective tissue disease"
"H00349","Trachoma","Trachoma is the leading infectious cause of blindness worldwide. Infections with serovars A, B, Ba, and C of Chlamydia trachomatis cause chronic keratoconjunctivitis in children with subsequent scarring and blindness in adults. Today, trachoma is largely found in poor, rural communities in low-income countries, particularly in sub-Saharan Africa.","Infectious disease"
"H02248","MEND syndrome","MEND syndrome (male EBP disorder with neurological defects) is an X-linked recessive condition in males with a phenotype remarkable for Dandy-Walker like congenital brain malformation, cataracts, collodion skin and cryptorchidism. Additional findings of hydrocephalus, dysplasia of the corpus callosum, cardiovascular, craniofacial and skeletal anomalies were regularly seen in patients. MEND syndrome is caused by EBP mutations. EBP is an integral membrane protein located mainly in the endoplasmic reticulum, which has dual functions as an enzyme converting cholestenol into lathosterol and as a high-affinity receptor for anti-ischaemic drugs.","Congenital malformation"
"H00991","Microcephalic osteodysplastic primordial dwarfism, type II (MOPD II)","Microcephalic osteodysplastic primordial dwarfism, type II (MOPD II) is an autosomal recessive condition characterized by severe intrauterine and postnatal growth failure, microcephaly, and disproportionate short stature due to short limbs. Characteristic skeletal abnormalities are seen.","Congenital malformation"
"H01843","Cerebrocostomandibular syndrome","Cerebrocostomandibular syndrome (CCMS) is a rare autosomal dominant multiple malformation disorder characterized by posterior rib gaps and Pierre Robin sequence (micrognathia, glossoptosis, and cleft palate). Affected patients often have respiratory difficulties, associated with upper airway obstruction, reduced thoracic capacity, and scoliosis. Key radiological findings are of a narrow thorax, multiple posterior rib gaps, and abnormal costo-transverse articulation. Mortality is 35%-50% in the first year of life and death is due to respiratory failure. However, general development progresses well once the initial respiratory problems are survived. Specific mutations in SNRPB, which encodes components of the major spliceosome, have been found to cause CCMS.","Congenital malformation"
"H01629","Chronic arterial occlusive disease","Chronic arterial occlusive disease is a highly prevalent peripheral vascular disorder. This disease is caused by arteriosclerosis obliterans (ASO), thromboangiitis obliterans (Buerger's disease), primary arterial thrombosis, embolism and so on. Of these, ASO is the most frequently encountered. Although differing clinically and pathologically, these diseases are similar in that they cause ischemia of tissues. The symptoms of chronic occlusive arterial disease result from impairment of blood flow to the extremities. Intermittent claudication is the commonest and usually the earliest symptom.","Vascular disease"
"H02058","Kohlschutter-Tonz syndrome","Kohlschutter-Tonz syndrome (KTS) is an autosomal recessive disease characterized by the combination of epilepsy, psychomotor regression, and amelogenesis imperfecta. It has been reported that KTS is caused by mutations in ROGDI, that plays an important role in neuronal development as well as amelogenesis.","Nervous system disease"
"H00159","Tangier disease","Tangier disease is an autosomal recessive disorder caused by mutation of ABCA1 gene leading to the accumulation of cholesterol in tissue macrophages and prevalent atherosclerosis.","Inherited metabolic disease; Nervous system disease"
"H00965","RAPADILINO syndrome","RAPADILINO syndrome is an abbreviation of its hallmark features: radial hypo-/aplasia, patellae hypo-/aplasia and cleft or highly arched palate, diarrhoea and dislocated joints, little size and limb malformation, nose slender and normal intelligence. It is an autosomal recessive disorder caused by mutations in human DNA helicase RECQL4. Unlike its allelic disorders Rothmund-Thomson syndrome and Baller-Gerold syndrome, RAPADILINO syndrome lacks poikiloderma.","Congenital malformation"
"H02093","Platelet-type von Willebrand disease","Platelet-type von Willebrand disease (PT-VWD) is an autosomal dominant bleeding disorder caused by gain-of-function mutations of GP1BA gene coding for the platelet surface glycoprotein Ib alpha protein, the receptor for the adhesive protein von Willebrand factor (VWF). PT-VWD is unique among platelet disorders because of platelet hyperresponsiveness rather than decreased function. In PT-VWD patients, platelets bind the VWF and agglutinate spontaneously. This results in thrombocytopenia and reduction of plasma VWF as platelets are removed from circulation. Of note, there is a very similar disorder, type 2B von Willebrand disease (VWD) [DS:H02092], to be taken into consideration in differential diagnosis.","Hematologic disease"
"H01616","Spinocerebellar degeneration","Spinocerebellar degenerations are neurodegenerative diseases that involve the cerebellum, brain stem, spinal cord, and basal ganglia to various degrees. Patients display limb and truncal ataxia, dysarthria, dysphagia, extrapyramidal sign, pyramidal sign, and autonomic disorder. Spinocerebellar degeneration includes both sporadic and hereditary forms. Most cases of sporadic spinocerebellar degeneration are now considered to be multiple system atrophy (MSA). Hereditary spinocerebellar degeneration includes autosomal dominant types and autosomal recessive types.","Neurodegenerative disease"
"H01424","Group A streptococcal pharyngitis","Group A streptococcal pharyngitis is an acute infection of the oropharynx and/or nasopharynx that is caused by group A streptococcus (Streptococcus pyogenes). Group A streptococcus is responsible for 5-15% of cases of pharyngitis in adults and 20-30% of cases in children, and is the most common cause of bacterial pharyngitis. The disorder is primarily a disease of children between 5 and 15 years of age, and, in temperate climates, it usually occurs in the winter and early spring. The onset of symptoms in patients is often abrupt. In addition to throat pain, symptoms may include fever, chills, malaise, headache, and particularly in younger children abdominal pain, nausea, and vomiting. Cough, coryza, and conjunctivitis are not typical symptoms of streptococcal pharyngitis, and, if present, they suggest an alternative cause such as a viral infection. In most persons, fever resolves within 3-5 days, and throat pain resolves within 1 week, even without specific treatment. Antibiotic treatment reduces the risk of subsequent development of acute rheumatic fever and suppurative complications.","Infectious disease"
"H00192","Xanthinuria","Xanthinuria is characterized by very low concentration of uric acid in blood and urine and high concentration of urinary xanthine. Hereditary xanthinuria is classified into three categories. Xanthinuria is classified into 2 groups, types I (XAN1) and II (XAN2). Patients with XAN1 lack only xanthine dehydrogenase/xanthine oxidase (XDH/XO) activity, while patients with type II lack both XDH/XO and aldehyde oxidase activities. It has been suggested that the mutation in the molybdenum cofactor sulfurase gene is responsible for XAN2.","Congenital disorder of metabolism"
"H01040","Bamforth-Lazarus syndrome","Bamforth-Lazarus syndrome is congenital hypothyroidism associated with choanal atresia, bifid epiglottis, and abnormal hair. It has been suggested that mutations in FOXE1 are associated with Bamforth-Lazarus syndrome. FOXE1 is a member of the forkhead/winged-helix family and functions as a thyroid transcription factor which likely plays a crucial role in thyroid morphogenesis.","Endocrine disease"
"H01272","Hypoplastic left heart syndrome","Hypoplastic left heart syndrome (HLHS) is a severe, uniformly fatal congenital heart defect typically characterized by hypoplasia of the left ventricular chamber and aorta in association with stenosis and/or atresia of the mitral and aortic valves. There is now strong evidence implicating multiple genetic loci for HLHS. Potential mutations in at least 4 genes, GJA1, NKX2-5, NOTCH1, and HAND1, have been associated with HLHS.","Congenital malformation"
"H00166","Hermansky-Pudlak syndrome","Hermansky-Pudlak syndrome (HPS) is a group of autosomal recessive disorders caused by defects in lysosome-related organelles and characterized by albinism and prolonged bleeding.","Congenital disorder of metabolism"
"H01888","Carpenter syndrome","Carpenter syndrome is a rare autosomal recessive multiple malformation disorder characterized by multisuture craniosynostosis and polysyndactyly of the hands and feet. Many other clinical features occur, and the most frequent include obesity, umbilical hernia, cryptorchidism, and congenital heart disease. Mutations of RAB23, that regulates vesicular transport, are present in the majority of cases. It has been reported that mutations in MEGF8 identify a Carpenter syndrome subtype associated with defective lateralization.","Congenital malformation"
"H02403","Angiostrongyliasis","Angiostrongyliasis is a food-borne parasitic zoonosis caused by nematode worms of the genus Angiostrongylus. Over 20 species of Angiostrongylus are currently recognized. Two species, A. cantonensis and A. costaricensis, are considered pathogenic agents when the larvae accidentally parasitise man. Angiostrongylus cantonensis was discovered in Guangzhou (Canton), China, in 1935. Angiostrongylus costaricensis was discovered in Costa Rica in 1967.","Infectious disease"
"H00354","Syphilis","Syphilis is one of the oldest recognized venereal infections caused by the spirochete Treponema pallidum subsp. pallidum. It is characterized by genital ulceration, skin rash, and development of serious systemic disease. Syphilis may also alter the course of HIV disease. Effective therapy is available but the incidence is increasing in many parts of the world.","Infectious disease"
"H01286","Microtia hearing impairment and cleft palate (MHICP)","Microtia is a congenital anomaly of the ear characterized by a small abnormally shaped outer ear. It is often associated with hearing loss. Syndromic form of microtia occur in conjunction with other abnormalities. The most common associated malformation is the cleft palate. It has been reported that a mutation in the HOXA2 homeobox gene causes microtia, severe hearing impairment, and partial cleft palate.","Congenital malformation"
"H02067","Boomerang dysplasia","Boomerang dysplasia (BD) is a perinatal lethal osteochondrodysplasia. Typical symptoms include micromelia with diminished ossification, and a characteristic bowed and boomerang like aspect of the long tubular bones. BD is caused by mutations in FLNB, the gene encoding the actin binding cytoskeletal protein, filamin B.","Congenital malformation"
"H00730","Familial idiopathic ventricular fibrillation","Idiopathic ventricular fibrillation (IVF) is a syndrome that causes sudden cardiac death in individuals with an apparently normal heart. It has been found a novel SCN5A missense mutation in one symptomatic IVF patient that did not exhibit the typical Brugada electrocardiogram (ECG). Recently, IVF linked to the DPP6 gene has been reported.","Cardiovascular disease"
"H00502","Pallister-Hall syndrome","Pallister-Hall syndrome is characterized by polydactyly, hypothalamic hamartoma, and malformations of other parts of the body. Cases with severe malformations are neonatally lethal. Pallister-Hall syndrome is caused by GLI3 mutations.","Congenital malformation"
"H02255","FDLAB syndrome","Facial dysmorphism, lens dislocation, anterior-segment abnormalities, and spontaneous filtering blebs (FDLAB) syndrome, also known as Traboulsi syndrome, is an autosomal recessive disorder. FDLAB syndrome is caused by mutations in ASPH that encodes aspartyl/asparaginyl beta-hydroxylase.","Congenital malformation"
"H00962","RIDDLE syndrome","RIDDLE (radiosensitivity, immunodeficiency, dysmorphic features, and learning difficulties) syndrome is an immunodeficiency disorder that primarily manifests as an immunoglobulin deficiency. The underlying genetic cause of this syndrome is defective RNF168 that functions to recruit DNA double-strand break (DSB) repair proteins, such as 53BP1 and BRCA1, to sites of DNA damage. As with patients with other DSB repair disorders, the RIDDLE patients also present with nonimmunological characteristics including short stature and motor control problems.","Immune system disease"
"H00708","Naegeli-Franceschetti-Jadassohn syndrome","Naegeli-Franceschetti-Jadassohn syndrome (NFJ) is a rare autosomal dominant disorder characterized by complete absence of dermatoglyphics, reticulate hyperpigmentation of the skin, palmoplantar keratoderma, and decreased sweating. Enamel defects and nail dystrophy have been observed in some patients. Decreased expression of keratin 14 in this disorder sensitizes the keratinocytes to TNF-alpha-induced apoptosis.","Congenital malformation"
"H02299","Arthrogryposis multiplex congenita","Arthrogryposis multiplex congenita (AMC) is a group of disorders characterized by non-progressive joint contractures from birth. There are various etiologies for AMC including genetic and environmental depends on the specific type. It has been reported that mutations in ERGIC1 cause AMC neuropathic type. ERGIC1 encodes a membrane protein which has a possible role in transport between endoplasmic reticulum and Golgi.","Congenital malformation"
"H01078","Fletcher factor deficiency","Fletcher factor deficiency, also called Prekallikrein deficiency, is an autosomal recessive heterozygous disorder of coagulation that is caused by defects in KLKB1. Although the patients had no abnormal bleeding tendency, their blood showed much prolonged activated partial thromboplastin time and delayed thromboplastin generation but normal prothrombin time.","Hematologic disease"
"H00996","Amish infantile epilepsy syndrome","Amish infantile epilepsy syndrome is an autosomal recessive, infantile-onset symptomatic epilepsy associated with developmental stagnation and blindness. A mutation in SIAT9, which is predicted to result in the premature termination of the GM3 synthase enzyme, has been identified.","Nervous system disease; Congenital disorder of metabolism"
"H01844","Diaphanospondylodysostosis","Diaphanospondylodysostosis (DSD) is a rare, recessively inherited, perinatal lethal skeletal disorder. It is one of a number of spinal dysostoses, which are a heterogeneous group of axial skeletal malformations occurring during blastogenesis with continued evolution after birth. The primary skeletal characteristics of the phenotype include a small chest, abnormal vertebral segmentation, and posterior rib gaps containing incompletely differentiated mesenchymal tissue. The spine is most prominently affected, with diaphanous, that is, translucent vertebrae, due to abnormal vertebral ossification and segmentation. A consistent feature of all described DSD cases are renal findings of dysplasia, nephrogenic rests or nephroblastomatosis, or cysts. It has been determined that DSD is due to mutations in the BMPER gene, which encodes the bone morphogenetic protein-binding endothelial cell precursor-derived regulator.","Congenital malformation"
"H00398","Influenza","Influenza is typically a self-limiting upper respiratory disease caused by three types of influenza viruses: influenza A, B, and C. Influenza A and B viruses cause highly contagious diseases whereas influenza C virus causes only mild upper respiratory tract illness. Influenza A virus is responsible for annual epidemics in humans with high mortality rates.","Infectious disease"
"H00505","FGFR3-related short limb skeletal dysplasia","FGFR3-related short limb skeletal dysplasias are a group of dwarfisms ranging from mild to lethal at the severe end. FGFR3 mutations cause these conditions by disrupting endochondral bone growth.","Congenital malformation"
"H02252","PEHO syndrome","The PEHO syndrome (progressive encephalopathy with oedema, hypsarrhythmia, and optic atrophy) is a rare autosomal recessive neurodegenerative disorder that presents in infancy with hypotonia, seizures, peripheral oedema, characteristic dysmorphic features, and poor visual response. It is characterized by extreme cerebellar atrophy due to almost total granule neuron loss. A missense mutation in ZNHIT3 was identified as the primary cause of PEHO syndrome.","Nervous system disease"
"H02060","Leptin receptor deficiency","Leptin receptor deficiency is an autosomal recessive condition that causes severe early-onset obesity and pituitary dysfunction. Mutations in LEPR gene encoding leptin receptor cause this disease.","Endocrine and metabolic disease"
"H00737","Peeling skin syndrome","Peeling skin syndrome (PSS) is a group of rare autosomal recessive disorders characterized by superficial detachment of the epidermal corneal layers. PSS can be divided into two main types, acral PSS (APSS) and generalized PSS. APSS involves the palmar, plantar and dorsal surfaces of hands and feet. Generalized PSS can be further divided into the non-inflammatory (type A) and the inflammatory (type B) forms. Several underlying genetic causes of PSS have been identified.","Congenital malformation"
"H02404","Capillariasis","Capillariasis is an infectious disease caused by nematode worms of the genus Capillaria. Intestinal capillariasis caused by Capillaria philippinensis appeared first in the Philippines in 1964. Major outbreaks have occurred in the Philippines and Thailand. It is believed that the means of transmission of C. philippinensis is by eating uncooked fish.","Infectious disease"
"H00353","Lyme borreliosis","Lyme borreliosis is the multisystem infectious disease caused by the tick-borne spirochetes Borrelia. Localized infection is typically manifested by erythema migrans skin lesions. A broad variety of peripheral nerve disorders (Lyme neuroborreliosis) can occur as well. Late Lyme borreliosis usually manifests as arthritis or the skin disorder known as acrodermatitis chronica atrophicans.","Infectious disease"
"H01281","Lathosterolosis","Lathosterolosis is an inborn error of cholesterol biosynthesis caused by mutations in SC5D gene encoding lathosterol 5-desaturase. It is characterized by a complex phenotype, including multiple congenital anomalies, mental retardation, and liver disease.","Congenital malformation"
"H00161","Smith-Lemli-Opitz syndrome","Smith-Lemli-Opitz syndrome is an autosomal recessive disorder caused by deficiency of 7-dehydrocholesterol reductase in cholesterol biosynthesis.","Inherited metabolic disease"
"H01275","Interleukin 1 receptor antagonist deficiency (DIRA)","Interleukin 1 receptor antagonist deficiency (DIRA) is a rare autosomal recessive autoinflammatory disease caused by mutations in IL1RN. The absence of interleukin 1 receptor (IL-1R) antagonist allows unopposed action of IL-1, resulting in life threatening systemic inflammation with skin and bone involvement.","Immune system disease"
"H00195","Adenine phosphoribosyltransferase deficiency","Adenine phosphoribosyltransferase deficiency is an autosomal recessive disorder of purine metabolism and causes urolithiasis due to accumulation of the insoluble purine 2,8-dihydroxyadenine.","Inherited metabolic disease; Urologic disease"
"H01047","Cysticercosis","Taenia solium, the pork tapeworm, is endemic in many poorer countries of Latin America, Africa, and Asia, where pigs are raised. Human infection with T. solium occurs after ingestion of undercooked pork infected with cysticerci. The larval stage of T. solium infects the human nervous system, causing neurocysticercosis. Neurocysticercosis causes acquired epilepsy and death.","Infectious disease"
"H01423","Penicillin-resistant Streptococcus pneumoniae infection","Streptococcus pneumoniae is a common causative pathogen in community-acquired respiratory tract infections (RTIs), including acute otitis media, acute bacterial exacerbations of chronic bronchitis, acute bacterial sinusitis, and community-acquired pneumonia. It is also a major cause of bacteremia. Pneumococcal antibiotic resistance towards different families of antibiotics, in particular, penicillin and the macrocodes, continues to be a much-debated issue. The main mechanism of resistance in clinical isolates of S. pneumoniae involves the alteration of penicillin target proteins, the so-called penicillin binding protein (PBPs), which cause reduced affinities and/or binding capacities for the antibiotic molecule.","Infectious disease"
"H02094","Carvajal syndrome","Carvajal syndrome is an autosomal recessive disorder, manifesting with dilated left ventricular cardiomyopathy, woolly hair, and palmoplantar keratoma. Carvajal syndrome is considered as a variant of Naxos disease. It is caused by homozygous mutation in the gene coding for desmoplakin. Recently, the autosomal dominant phenotype associated with leukonychia and oligodontia was reported.","Congenital malformation"
"H01611","Alcohol dependence","Alcohol dependence (AD) is a chronic but often disease that includes problems in controlling one's drinking, being preoccupied with alcohol, continuing to use alcohol even when it causes problems, having to drink more to get the same effect (physical dependence), or having withdrawal symptoms when one rapidly decreases or stops drinking. The contribution of genetic factors to the development of AD is high. The best classical candidate genes for AD are alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Both genes are involved in enzymatic degradation of alcohol. Recent genome-wide association studies (GWAS) have reported that the most robust associations for AD have been with such enzyme genes, especially ALDH2 in East Asian populations and ADH1B in European American and African American populations.","Mental and behavioural disorder"
"H02069","SADDAN","SADDAN (severe achondroplasia with developmental delay and acanthosis nigricans) is a rare skeletal dysplasia caused by a Lys650Met mutation in fibroblast growth factor receptor 3 (FGFR3).","Congenital malformation"
"H00168","Oculocutaneous albinism","Oculocutaneous albinism (OCA) is a genetically heterogeneous congenital disorder of melanin biosynthesis characterized by decreased or absent pigmentation in the hair, skin, and eyes.","Inherited metabolic disease; Skin and connective tissue disease; Eye disease"
"H01886","Van den Ende-Gupta syndrome","Van den Ende-Gupta syndrome (VDEGS) is a rare hereditary disorder with characteristic craniofacial and skeletal manifestations. Characteristic features of VDEGS include blepharophimosis, malar hypoplasia, narrow nasal bridge, convex nasal ridge everted lower lip, arachnodactyly, camptodactyly, slender ribs, underdeveloped glenoid fossa, and mild bowing of long bones, while growth and development are normal. The pattern of inheritance has been suggested to be autosomal recessive, but several reports have suggested it to be autosomal dominant.","Congenital malformation"
"H00954","Macular corneal dystrophy","Macular corneal dystrophy (MCD), inherited in an autosomal recessive fashion, is the least common but severe form of stromal dystrophy characterized by superficial gray-white corneal opacities that progressively increase to involve the entire corneal stroma from limbus to limbus. Patients experience progressive decreased vision and irritation as the diseases worsens, and will have vision severely affected by the third to fourth decade of life. It has been shown that a specific sulfation step in the production of keratan sulfate, the major glycosaminoglycan of the corneal stroma, is impaired in MCD. This results in the accumulation of glycosaminoglycans that form the abnormal deposits. Mutations in the CHST6 gene, which encodes an enzyme that catalyzes the sulfation of keratan sulfate, are responsible for most cases of MCD.","Nervous system disease"
"H01288","Mosaic variegated aneuploidy syndrome","Mosaic variegated aneuploidy syndrome (MVA) is a rare autosomal recessive disorder characterized by mosaic aneuploidies, diverse phenotypic abnormalities and predisposition to cancer. MVA is due to defective cell division, leading to aberrant disjunction of chromosomes during mitosis. It has been reported that mutations of the BUB1B, CEP57, and TRIP13 genes cause MVA.","Chromosomal abnormality"
"H01872","Microcephaly-capillary malformation syndrome","Microcephaly-capillary malformation (MIC-CAP) syndrome is a autosomal recessive congenital neurocutaneous disorder characterized by severe microcephaly with progressive cortical atrophy, intractable epilepsy, profound developmental delay, and multiple small capillary malformations on the skin. In addition, affected patients have variable dysmorphic facial features and hypoplastic distal phalanges. Dysmorphic features include whorled hair pattern, low frontal hairline, hypertelorism, ptosis, epicanthic folds, long palpebral fissures, cleft palate, thin upper lip, short nose, low-set ears, and maxillary hypoplasia. Almost all patients exhibit variable degrees of distal limb abnormalities. Mutations in the STAMBP gene have been identified as causative in the pathogenesis of this syndrome.","Congenital malformation"
"H01618","Pituitary gigantism","Pituitary gigantism is very rare conditions resulting from excessive secretion of growth hormone (GH). Most cases are due to benign pituitary adenomas. Nonadenomatous GH excess is exceptional but occasionally occurs in patients with multiple endocrine neoplasia syndrome type 1 (MEN1), Carney complex, or McCune-Albright syndrome. The clinical manifestations may include increased growth velocity with tall stature, enlargement of the hands and feet, excessive perspiration, coarsening of facial features, and headaches. It has been reported that duplication of GPR101 probably causes gigantism and acromegaly. Therapeutic modalities for the treatment of pituitary gigantism include surgery, medication and radiation.","Endocrine disease"
"H00365","Herpes simplex virus infection","Herpes simplex virus infection is caused by Herpes simplex virus type 1 (HSV-1) and Herpes simplex virus type 2 (HSV-2), Simplex viruses in the order Herpesvirales of dsDNA viruses. Humans are the only natural host and reservoir for the HSV virus. HSV are human neurotropic viruses that establish latent infection in dorsal root ganglia (DRG) for the entire life of the host. HSV infects the human host via mucosal surfaces or damaged skin, and most primary infections are asymptomatic. HSV-1 is mainly associated with orofacial lesions, yet it is also the cause of infectious blindness and viral encephalitis in adults. HSV-2 is mainly associated with genital lesions and neonatal encephalitis.","Infectious disease"
"H02432","Butyrylcholinesterase deficiency","Hereditary Butyrylcholinesterase deficiency (BCHED) results from the mutations of BCHE gene. Butyrylcholinesterase is an ester hydrolase produced mainly by the liver, hydrolyzes certain short-acting neuromuscular blocking agents, like succinylcholine and mivacurium that are widely used during anesthesia. Patients with BCHED are possibly in danger of postanesthetic apnea.","Congenital disorder of metabolism"
"H01085","Diphyllobothriasis","Diphyllobothriasis is a parasitosis caused by the tapeworms of the genus Diphyllobothrium. It has been known as intestinal parasites of humans for a long time and has shown a reemergence in some countries such as Russia and Japan. The worm is acquired by eating raw or poorly cooked fish including salted or marinated fillets. Many infections with this parasite are reported to be mild or asymptomatic.","Infectious disease"
"H00157","Hyperlipoproteinemia, type V","Type V hyperlipoproteinemia is an autosomal recessive disorder caused by deficiency of apolipoprotein A-V and characterized by an increase of chylomicrons and VLDL and a decrease of LDL and HDL in the plasma after a fast.","Inherited metabolic disease"
"H02264","Palmoplantar keratoderma, Nagashima type","Palmoplantar keratoderma Nagashima type (PPKN) is an autosomal recessive nonsyndromic diffuse palmoplantar keratosis characterized by diffuse hyperkeratosis with redness, expanding on to the dorsal surfaces of the palms and feet and the Achilles tendon area. Its clinical manifestations are similar to but milder than those of mal de Meleda. It has been reported that mutations in SERPINB7, encoding a member of the serine protease inhibitor, cause PPKN.","Congenital malformation"
"H00533","Hereditary hemorrhagic telangiectasia","Hereditary hemorrhagic telangiectasia (HHT), also known as Osler disease, is an autosomal dominant vascular dysplasia characterized by severe recurrent nasal and gastrointestinal bleeding and cutaneomucosal telangiectases. HHT is often associated with arteriovenous malformations in the pulmonary, hepatic, cerebral, and spinal circulations. The disease arises from defects in TGF-beta signaling. It has been reported that mutations in SMAD4 cause the combined juvenile polyposis and HHT (JPHT) syndrome.","Cardiovascular disease"
"H00701","Congenital fiber type disproportion","Congenital fiber type disproportion (CFTD) is a relatively rare subtype of congenital myopathy characterized by hypotonia and generalized muscle weakness. Pathologic diagnosis of CFTD is based on the presence of type 1 fiber hypotrophy of at least 12% in the absence of other notable pathological findings, in addition to a clinical presentation typical of congenital myopathies. CFTD is a genetically heterogenous condition with X-linked, autosomal dominant, and autosomal recessive inheritance patterns. Mutations of the ACTA1 and SEPN1 genes have been identified in a small percentage of CFTD cases, and recently mutations in the TPM3 gene were also found to cause CFTD.","Nervous system disease; Musculoskeletal disease"
"H02056","Dubin-Johnson syndrome","Dubin-Johnson syndrome (DJS) is a rare autosomal recessive disorder characterized by chronic conjugated hyperbilirubinemia and impaired hepatobiliary transport of non-bile salt organic anions. It is caused by mutations in ABCC2, a canalicular bilirubin glucuronide and xenobiotic export pump.","Congenital disorder of metabolism"
"H02290","Retinal dystrophy and iris coloboma with congenital cataract","Retinal dystrophy and iris coloboma with congenital cataract (RDICC) is an autosomal dominant condition of retinal dystrophy and bilateral coloboma, present in varying degrees. A mutation in microRNA-204 (miR-204) has been identified in all affected individuals. It has been demonstrated that miR-204 is necessary for normal photoreceptor function.","Nervous system disease"
"H01415","Donovanosis","Donovanosis (granuloma inguinale) is an acquired chronic, slowly progressive, mildly contagious disease caused by Klebsiella granulomatis that was called Calymmatobacterium granulomatis. This sexually transmitted disease is characterized by granulomatous ulceration of the genitalia and neighboring sites, with little or no tendency to spontaneous healing.","Infectious disease"
"H01243","Huntington disease-like syndrome","Huntington disease (HD), which is caused by a triplet-repeat expansion in the IT15 gene (also known as huntingtin or HD), accounts for about 90% of cases of chorea of genetic etiology. In recent years, several other distinct genetic disorders have been identified that can present with a clinical picture indistinguishable from HD, termed HD-like (HDL) syndromes. So far, four genes associated with HDL syndromes have been identified, including the prion protein gene (HDL1), the junctophilin 3 gene (HDL2) and, the gene encoding the TATA box-binding protein (HDL4).","Neurodegenerative disease"
"H00391","Henipavirus infection","Hendra virus and Nipah virus are members of a new genus, Henipavirus, in the emerging family Paramyxoviridae. They are bat-borne paramyxoviruses which are responsible for severe disease with high mortality rates (50-100%).","Infectious disease"
"H01071","Acute alcohol sensitivity","Aldehyde dehydrogenases (ALDHs) are important enzymes that eliminate toxic aldehydes by catalysing their oxidation to non-reactive acids. It is reported that a deficiency in the ALDH2 is associated with the alcohol flush reaction. More than 40% of the East Asians population carries a common ALDH2 mutant allele, which results in a dramatic reduction in the enzymatic activity when compared with the wild-type allele.","Inherited metabolic disease"
"H01049","Gordonia bronchialis infection","Gordonia species are aerobic actinomycetes recently recognized as causing human disease in immunocompromised and immunocompetent patients. Gordonia bronchialis has been isolated from cases of bacteremia, pleural infection, intraventricular shunt, sternal wound, and breast abscess.","Infectious disease"
"H01875","Infantile hepatic hemangioma","Infantile hepatic hemangioma (IHH), although rare, is the most common benign hepatic vascular tumor in the first year of age. They are sub-classified in focal, multiple and diffuse lesions, based on degree of unaffected liver parenchyma. Most lesions are clinically silent and self-limiting, whereas others can become symptomatic, manifesting as cardiac failure, fulminant hepatic failure and abdominal compartment syndrome. The term IHH is preferred to 'hemangioendothelioma' because the clinical and biologic behavior is similar to infantile hemangiomas [DS:H01482] that affect the skin and other parts of the body.","Vascular disease"
"H01881","Complex cortical dysplasia with other brain malformations","Complex cortical dysplasia with other brain malformations (CDCBM) is a disorder of aberrant neuronal migration and disturbed axonal guidance. Patients exhibit mental retardation, strabismus combined with nystagmus, axial hypotonia, and spasticity. The severity of mental retardation ranged from mild to severe. Complex cortical malformations associated with mutations in tubulin and motor proteins of the kinesin genes has been reported.","Congenital malformation"
"H00953","Gelatinous drop-like corneal dystrophy","Gelatinous drop-like corneal dystrophy (GDCD) is a rare autosomal recessive dystrophy characterized by multiple prominent milky-white gelatinous mulberry-shaped nodules formed beneath the corneal epithelium during the first decade of life. Clinical symptoms include photophobia, foreign body sensation, and decreased vision. Fusiform deposits similar to those in lattice corneal dystrophy [DS:H00956] may also form in the deeper stroma. GDCD has been linked to mutations in the TACSTD2 gene. TACSTD2 is a cell surface phosphoglycoprotein as well as a substrate for protein kinase C. Mutations in the gene lead to a truncated protein which is thought to trigger amyloid formation in the cornea.","Nervous system disease"
"H00739","Ichthyosis with hypotrichosis","Ichthyosis with hypotrichosis is a syndromic form of autosomal recessive congenital ichthyoses associated with abnormal hair. Sparse scalp hair, wrinkled skin, and corneal abnormalities are observed in patients with the disease. It is linked ST14 encoding the matriptase serine protease.","Congenital malformation"
"H01076","Alpha-methylacetoacetic aciduria","Alpha-methylacetoacetic aciduria/3-Ketothiolase deficiency is an autosomal recessive error of isoleucine and ketone body catabolism caused by a deficiency of mitochondrial acetoacetyl-CoA thiolase. The patients present with intermittent ketoacidotic episodes and urinary excretion of 2-methylacetoacetate, 2-methyl-3-hydroxybutyrate, and tiglylglycine.","Inherited metabolic disease"
"H00998","Alternating hemiplegia of childhood","Alternating hemiplegia of childhood (AHC) is a rare disorder with onset before 18 months of age. The earliest manifestations of AHC are recurrent bilateral attacks of hemiplegia lasting minutes to days, abnormal ocular movements, and autonomic disturbances. A characteristic feature of AHC is the disappearance of all abnormalities when the child falls asleep.","Nervous system disease"
"H01244","T+B+Severe combined immunodeficiencies (SCIDs)","Recently, several groups reported a novel clinical and immunological phenotype of T+B+NK+SCID (severe combined immunodeficiencies) associated with recessive RAG1 hypomorphic mutations. The immunological phenotype consists of the oligoclonal expansion of TCR-gamma/delta T cells combined with TCR-alpha/beta T cell lymphopenia. The clinical phenotype consists of severe, disseminated cytomegalovirus (CMV) infection and autoimmune blood cell manifestations.","Primary immunodeficiency"
"H00396","Mumps","Mumps is an acute systemic viral infection classically manifested by inflammation of parotid glands and fever. Mortality is rare, but it is often accompanied by more serious complications such as aseptic meningitis, pediatric deafness, and orchitis.","Infectious disease"
"H01620","Raynaud syndrome","Raynaud syndrome (RS) is characterized by episodic digital ischemia induced by cold or emotional stress. Pathophysiologic mechanisms include temporary vasospasm and fixed digital artery obstruction. Although the underlying pathophysiological mechanism is unclear, alterations in activity of the peripheral adrenoceptor have been implicated, specifically an enhanced smooth muscle contraction due to overexpression or hyperactivity of postsynaptic alpha 2 receptors. RS can occur as an isolated entity, historically referred to as Raynaud disease or now primary RS, or in association with other conditions, most frequently the connective tissue diseases (eg, scleroderma [DS:H01492], systemic lupus erythematosus [DS:H00080], rheumatoid arthritis [DS:H00630], and Sjogren's syndrome [DS:H01502]), often referred to as Raynaud phenomenon or secondary RS. The diagnosis is mainly clinical, based on patient descriptions of skin changes. Therapy has been focused on the use of general vasodilation strategies.","Cardiovascular disease"
"H02297","CLAPO syndrome","CLAPO syndrome is a rare vascular disorder characterized by capillary malformation of the lower lip, lymphatic malformation predominant on the face and neck, asymmetry, and partial/generalized overgrowth. CLAPO is caused by activating mutations in PIK3CA.","Congenital malformation"
"H01412","Perlman syndrome","Perlman syndrome is a rare autosomal recessive overgrowth disorder characterized by polyhydramnios with neonatal macrosomia, visceromegaly, distinctive facial appearance, renal dysplasia, nephroblastomatosis, and predisposition to Wilms tumor. It has been reported that germline mutations in DIS3L2 cause this disease.","Congenital malformation"
"H00706","Bart-Pumphrey syndrome","Bart-Pumphrey syndrome is an autosomal dominant disorder characterized by congenital deafness and palmoplantar hyperkeratosis. Patients also display knuckle pads and leukonychia. GJB2, the gene encoding connexin-26, is mutated in the disease.","Congenital malformation"
"H02051","May-Hegglin anomaly","The May-Hegglin anomaly (MHA) is a rare autosomal dominant disease characterized by neutrophils with abnormal cytoplasmic inclusions, large platelets, and variable thrombocytopenia. It has been suggested that mutations in MYH9 result in this disease.","Cardiovascular disease"
"H02263","Focal nonepidermolytic palmoplantar keratoderma","Focal nonepidermolytic palmoplantar keratoderma (FNEPPK) is a genetically heterogeneous phenotype characterized by the presence, on the palms and soles, of circumscribed calluses. These can be painful. It has been reported that mutations in keratin 16 (KRT16) and TRPV3 gene cause FNEPPK. Both of them are inherited in an autosomal dominant manner.","Congenital malformation"
"H00534","Cerebral cavernous malformation","Cerebral cavernous malformations (CCM) are vascular malformations of the central nervous system comprising enlarged caverns with a single layer of endothelium, which easily lead to cerebral hemorrhages. The disease present as either sporadic or autosomal dominant conditions and is linked to three genes KRIT1, MGC4607, and PDCD10. Mutations in KRIT1 impair its interaction with ICAP-1 alpha, and influence beta 1 integrin-dependent angiogenesis.","Developmental disorder; Vascular disease"
"H01082","Phosphoserine aminotransferase deficiency","Phosphoserine aminotransferase (PSAT) deficiency is a disorder of serine biosynthesis characterized biochemically by low plasma and CSF concentrations of serine and glycine and clinically by intractable seizures, acquired microcephaly, hypertonia, and psychomotor retardation. The biochemical and clinical features of PSAT deficiency shared some of the features of 3-PGDH deficiency [DS:H01079]. Mutations in the PSAT1 gene have been identified.","Inherited metabolic disease"
"H00150","Danon disease","Danon disease is an X-linked disorder caused by deficiency of lysosomal-associated membrane protein Lamp2 and resulting in cardiomyopathy, myopathy, and mental retardation. Originally Danon disease was classificatied as a variant of glycogen storage disease II (Pompe disease). However, at present, it is considered that Danon disease is not a glycogen storage disease because the disease is caused by the primary deficiency of a lysosomal membrane protein instead of a glycolytic enzyme and detailed pathological features are different from those of Pompe disease.","Inherited metabolic disease; Nervous system disease; Lysosomal storage disease"
"H00362","Giardiasis","Giardiasis is one of the most common parasite-induced diarrhea caused by the protozoan parasite Giardia lamblia. Infection is transmitted by ingestion of contaminated water or food, or by person-to-person contact, affecting children, pregnant women, the immunocompromised individuals, and people living with poor sanitation facilities.","Infectious disease"
"H02435","Deafness-infertility syndrome","Deafness-infertility syndrome (DIS) is an autosomal recessive contiguous gene deletion syndrome characterised by deafness and sperm dysmotility. This syndrome is caused by the deletion of contiguous genes at 15q15.3. The deleted region involves two genes, CATSPER2 and STRC, that are expressed in the sperm and inner ear, respectively.","Congenital malformation"
"H02495","Congenital megabladder","Congenital megabladder (MGBL) is characterized by a massively dilated urinary bladder with disrupted smooth muscle in its wall. It has been reported that loss of function mutations in myocardin cause this disease. Myocardin is required for maintenance of vascular and visceral smooth muscle homeostasis during postnatal development.","Congenital malformation"
"H01210","Hypomagnesemia","Hypomagnesemia (HOMG) is defined as a serum magnesium level less than 1.8 mg/dl. Hypomagnesemia may result from inadequate magnesium intake, increased gastrointestinal or renal losses, or redistribution from extracellular to intracellular space.","Congenital disorder of metabolism"
"H01022","Diseases of the tricarboxylic acid cycle","Diseases of the tricarboxylic acid cycle (TCA cycle) constitute a group of rare human diseases that affect core mitochondrial metabolism. The Fumarase deficiency is caused by impairment of the fumarate hydratase enzyme. The symptoms of the disorder include developmental delay, severe mental retardation, language impairment, seizures and dysmorphic facial features. The succinate dehydrogenase deficiency affects mitochondrial complex II, which links the TCA cycle with the electron transport chain. The phenotype is highly variable and can include Leigh syndrome, leukodystrophy, cardiomyopathy and mental and motor skill deterioration. The alpha-ketoglutarate dehydrogenase deficiency is extremely rare and characterised by encephalopathy and hyperlactatemia resulting in death in early childhood.","Metabolic disease"
"H00594","Distal myopathy","Distal myopathies (MPD) are a group of heterogeneous inherited primary muscle disorders classified into one broad category due to the presentation of weakness involving the distal skeletal muscles. Clinical presentation is characterized by progressive muscular weakness and atrophy beginning in the hands, forearm, lower legs or feet. Currently almost 20 different entities of distal muscular dystrophies have been genetically determined. Half of the genes have been associated with distal phenotypes only, whereas the other genes can manifest also with other than distal phenotypes. Most of the genes code for structural and functional components of the sarcomere. The genes responsible for the pathologically defined category of myofibrillar myopathy are frequently display a distal phenotype.","Nervous system disease; Musculoskeletal disease"
"H01446","Propionibacterium acnes infection","The anaerobic Gram-positive bacterium Propionibacterium acnes which forms part of the normal resident human microbiota of the skin, oral cavity, and gastrointestinal and genitourinary tracts. The organism is an opportunistic pathogen most widely known for its association with acne vulgaris but it also causes bacterial keratitis and endophthalmitis after ophthalmic surgery, and is increasingly recognized as a significant cause of medical device-related infections.","Infectious disease"
"H01674","Ankylosing spondylitis","Ankylosing spondylitis (AS), formerly also known as Bechterew's disease, is a rheumatic disease of the axial skeleton that mainly affects the spine and the sacroiliac joint in the pelvis. AS is one of a group of inflammatory diseases, called spondyloarthritides, which share features. This disease is characterized by erosion, sclerosis, and ossification, which may result in complete fusion and rigidity of the spine. Regarding extra-articular manifestations, the most frequent is anterior uveitis. The major functional losses occur during the first 10 years of disease. It usually begins in the second or third decade of life, preferentially in HLA-B27-positive Caucasian males. Its etiology and pathogenesis are not completely understood, but the most prevalent hypothesis involves immune mediation as its major mechanism, including several cytokines. To date, more than 40 genetic variants have been identified that influence the risk of developing AS, including HLA alleles such as HLA-B27. Non-steroid anti-inflammatory drugs (NSAIDs) are used to reduce pain and inflammation. Additional disease-modifying anti-rheumatic drugs (DMARDs) are prescribed to slowdown disease progression. The most frequently applied biological agents approved for AS are TNF alpha inhibitors. The IL-17 inhibitor secukinumab has been recently approved for moderate-to-severe plaque psoriasis, psoriatic arthritis, and AS.","Immune system disease; Musculoskeletal disease"
"H00560","Pseudoxanthoma elasticum","Pseudoxanthoma elasticum (PXE) is a multisystem genetic disorder characterized by aberrant mineralization of elastic fibers in connective tissue affecting the skin, eyes and the arterial blood vessels. The mutated gene is identified as ABCC6, an ATP-binding cassette transporter. Recently, mutations in the GGCX gene in a family with PXE-like phenotypes has been reported.","Congenital malformation"
"H02237","AMP deaminase deficiency","AMP deaminase is widely distributed in various mammalian cells and tissue-specific isozymes were found. Muscle specific AMP deaminase is also known as myoadenylate deaminase (MAD). MAD deficiency (MADD) was discovered in patients with muscle weakness and cramping after exercise, and the mutations in AMP deaminase gene (AMPD1) have been identified. Although a point mutation on the human erythrocyte AMPD3 has also been identified, erythrocyte AMP deaminase deficiency was clinically asymptomatic.","Congenital disorder of metabolism"
"H02005","Mitochondrial complex II deficiency","Mitochondrial complex II (CII, succinate dehydrogenase complex) deficiency is a rare cause of mitochondrial respiratory chain defects. CII functions in the TCA cycle and in the mitochondrial electron transport chain (ETC). Four structural subunits (SDHA, SDHB, SDHC and SDHD) and two known assembly factor genes (SDHAF1 and SDHAF2) are all nuclear-encoded. Mutations in SDHA, SDHD, and SDHAF1 have been found in patients. CII deficiency has a variable phenotype. Brain imaging is abnormal in majority of the patients and consists of leukoencephalopathy, Leigh syndrome or cerebellar atrophy.","Inherited metabolic disease; Mitochondrial disease"
"H00752","Ankyloblepharon-ctodermal defects-cleft lip/palate (AEC) syndrome and Rapp-Hodgkin syndrome","Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome (also known as Hay-Wells syndrome) and Rapp-Hodgkin syndrome are rare ectodermal dysplasias characterized by ankyloblepharon filiforme adnatum and cleft lip/palate. Ectodermal findings include hair, nail, teeth and sweat gland dystrophies.","Congenital malformation"
"H01680","Chronic pancreatitis","Chronic pancreatitis is a progressive inflammatory disease of the pancreas that will finally result in both exocrine and endocrine insufficiency. Chronic pancreatitis develops gradually and worsens over time, resulting in permanent organ damage. It is usually caused by recurrent episodes of pancreatic necro-inflammation, leading to pancreatic atrophy and dysfunction. It manifests clinically as maldigestion, weight loss, abdominal pain and eventually diabetes. Six major etiologies for chronic pancreatitis have been identified, namely toxic-metabolic (to include alcohol), idiopathic, genetic, autoimmune, recurrent and severe acute pancreatitis, and obstruction. Oral protease inhibitors are currently used as a medical treatment for chronic pancreatitis.","Pancreas disease"
"H02461","Neurodevelopmental disorder with microcephaly","Neurodevelopmental disorder (NED) with microcephaly is a group of syndromic neurodevelopmental disorders. Most of them have complications in addition to microcephaly. Several underlying genetic causes of these diseases have been identified.","Congenital malformation"
"H00336","Gas gangrene","Gas gangrene is a rare and devastating wound infection. The Clostridium perfringens, septicum, and histolyticum are the principal causes of trauma-associated gas gangrene. It is characterized by fever, pain, edema, myonecrosis and gas production. Recently, there has also been an increased incidence of spontaneous gas gangrene caused by Clostridium septicum.","Infectious disease"
"H00938","Factor XI deficiency","Factor XI (FXI) deficiency is an injury-related bleeding disorder common in Ashkenazi Jews and rare worldwide. FXI deficiency is characterized by infrequent spontaneous bleeding, but increased risk of hemorrhagic complications especially after trauma or surgery. More than 180 mutations in the FXI gene have been reported in patients with FXI deficiency.","Hematologic disease"
"H00104","Alternative complement pathway component defects","The alternative pathway is antibody independent and relies on native C3 undergoing minimal spontaneous hydrolysis. Hydrolyzed C3 binds factor B. Factor B, when bound to hydrolyzed C3, is cleaved by factor D into Ba and Bb. Hydrolyzed C3Bb is responsible for a constant low level of C3 cleavage into C3b. If C3b binds to an appropriate surface, factor B will bind with C3b to form C3bBb, a highly efficient C3-cleaving enzyme. This overall series of successive proteolytic steps is enhanced by the serum protein properdin, which stabilizes protein:protein interactions during the process. Factor H is essential in controlling the function of the alternative pathway by inhibiting the formation of and degrading C3bBb. Deficiencies of alternative pathway-specific components are rare, and usually lead to an increased frequency of Neisseria infections.","Primary immunodeficiency"
"H00799","CEDNIK syndrome","CEDNIK (Cerebral dysgenesis, neuropathy, ichthyosis and keratoderma) syndrome is a rare condition that shows severe developmental failure of the nervous system and the epidermis. Clinical manifestations include microcephaly, cerebral dysgenesis, facial dysmorphism, palmoplantar keratoderma, and ichthyosis. Decreased expression of SNAP29, a member of the SNARE family of proteins, is linked to abnormal lamellar granule maturation and abnormal epidermal differentiation.","Congenital malformation"
"H01479","Castleman disease","Castleman disease is a rare lymphoproliferative disorder with two primary subtypes that vary in presentation and course. Unicentric Castleman disease is localized and carries an excellent prognosis. Multicentric Castleman disease can be associated with HIV and human herpesvirus-8 and is characterized by generalized lymphadenopathy and systemic symptoms, such as fever, fatigue, anorexia, anemia, and cachexia. Castleman disease is unique in that dysregulated secretion of interleukin-6 (IL-6) plays a central pathogenetic role, although the exact events precipitating the oversecretion of IL-6 are unknown. Recently, two antibody-based therapeutics targeting components of the IL-6/IL-6R complex have been approved for the treatment of Castleman disease. Tocilizumab is a monoclonal antibody directed against the IL-6 receptor, and siltuximab is a monoclonal antibody specific for IL-6.","Immune system disease"
"H01821","Spondylometaphyseal dysplasia with cone-rod dystrophy","Spondylometaphyseal dysplasia with cone-rod dystrophy (SMD-CRD) is a rare presumed autosomal-recessive disorder with postnatal growth deficiency leading to profound short stature; rhizomelia with bowing of the lower extremities; platyspondyly with anterior vertebral protrusions; progressive metaphyseal irregularity and cupping with shortened tubular bones; and early-onset, progressive visual impairment associated with a pigmentary maculopathy and electroretinographic evidence of cone-rod dysfunction. Spondylometaphyseal dysplasias (SMDs) are a heterogeneous group of disorders radiologically characterized by platyspondyly and metaphyseal dysplasia. Extra-skeletal abnormalities associated with SMDs are uncommon. In 2004, a unique form of SMD associated with cone-rod dystrophy (CRD) was described and defined as SMD-CRD. Loss-of-function mutations in PCYT1A have been reported as the cause of SMD-CRD.","Congenital malformation"
"H00907","Kleefstra syndrome","Kleefstra syndrome (KLEFS), also known as the 9q subtelomeric deletion syndrome is characterized by intellectual disability, childhood hypotonia, and distinctive facial features. About 75% of Kleefstra syndrome is caused by microdeletion of 9q34.3 and 25% by intragenic EHMT1 mutation. Recently, a few patients with loss of function mutations affecting the histone methyltransferase KMT2C were reported.","Congenital malformation"
"H00309","Multidrug-resistant Acinetobacter infection","Acinetobacter baumannii has emerged as a worldwide problem as a nosocomial pathogen in hospitalized patients. It can cause bacteremia, pneumonia, meningitis, urinary tract infection, wound infection, and nosocomial infections. Isolates resistant to almost all commercially available antimicrobials have been identified.","Infectious disease"
"H02208","Pantothenate kinase-associated neurodegeneration","Pantothenate kinase associated neurodegeneration (PKAN), also known as Hallervorden-Spatz disease, is an autosomal recessive neurodegenerative disorder associated with iron accumulation in the brain. Clinical features include extrapyramidal dysfunction, onset in childhood, and a relentlessly progressive course. Mutations in PANK2 gene encoding the mitochondrial pantothenate kinase have been found in patients.","Nervous system disease"
"H00103","Late complement pathway defects","Late complement component (the final common pathway C5b-C9 components) deficiencies are all inherited in an autosomal recessive manner. In all cases, homozygous recessive patients have greatly reduced levels of the respective complement component. Generally, patients with deficiencies of C5, C6, C7, or C8 are particularly susceptible to systemic infections with Neisseria meningitidies and N. gonorrhoeae. Infections are rarely fulminant but are often recurrent and frequently involve unusual serotypes of the organism.","Primary immunodeficiency"
"H02466","Rajab interstitial lung disease with brain calcification","Rajab interstitial lung disease with brain calcification (RILDBC) is severe growth restriction with combined brain, liver and lung involvement. Mutations in genes encoding phenylalanyl-tRNA synthetases cause this disease.","Congenital malformation"
"H00331","Vancomycin-resistant Staphylococcal aureus (VRSA) infection","Vancomycin-resistant Staphylococcus aureus (VRSA) represents strains of S. aureus that have ability of resistance to the glycopeptide antibiotic vancomycin. S. aureus is the most common cause of nosocomial infections. The glycopeptides-notably vancomycin-have traditionally been the mainstay of treatment of methicillin-resistant S. aureus (MRSA) but overuse has led to the emergence of vancomycin-intermediate and vancomycin-resistant S. aureus (VISA and VRSA, respectively). Limited treatment options make resistant S. aureus infections particularly difficult and costly to treat, especially in areas of poor antibiotic penetration, such as joint spaces and the central nervous system. A gene known as vanA is a major determinant, which is transferable and can be acquired by sensitive bacteria from resistant organisms.","Infectious disease"
"H02002","Cryohydrocytosis","Cryohydrocytosis (CHC) is an exceedingly rare condition which shows a mild stomatocytic haemolytic state with hyperbilirubinaemia. Red blood cells from patients with CHC have increased membrane permeability to sodium and potassium ions, which is particularly pronounced at 0 degrees Celsius.","Hematologic disease"
"H00755","Acrokeratosis verruciformis","Acrokeratosis verruciformis is a rare autosomal dominant genodermatosis characterized by multiple planar wart-like lesions on the hands and feet. The lesions are usually present at birth. Mutations in ATP2A2 encoding the calcium pump in sarcoendoplasmic reticulum have been identified.","Congenital malformation"
"H01687","Extrahepatic portal vein obstruction","Extrahepatic portal vein obstruction (EHPVO) is a vascular disorder of liver characterized by obstruction and cavernomatous transformation of portal vein with or without the involvement of intrahepatic portal vein, splenic vein, or superior mesenteric vein. The most characteristic imaging manifestation is the formation of porto-portal collaterals that allow hepatopetal flow. Gradually there is organization and temporal evolution of thrombus with formation of portal collaterals termed 'cavernoma' aiming to bypass the obstructed portal vein. Patients generally present in childhood with multiple episodes of variceal bleed and EHPVO is the predominant cause of paediatric portal hypertension (PHT) in developing countries.","Cardiovascular disease"
"H00567","Limb-girdle muscular dystrophy 1C","Limb-girdle muscular dystrophy (LGMD) is a clinically and genetically heterogeneous group of myopathies characterized by a progressive weakness of the pelvic and shoulder girdle musculature. It has been reported that loss-of-function mutations in caveolin-3 gene are associated with a form of muscular dystrophy, LGMD1C. Caveolins are the principal protein components of caveolae which represent appendages or sub-compartments of plasma membranes.","Nervous system disease; Musculoskeletal disease"
"H02230","X-linked cardiac valvular dysplasia","X-linked cardiac valvular dysplasia is characterized by mitral valve dystrophy frequently associated with degeneration of the aortic valves affecting males and, to a lower severity, females. It has been reported that mutations in FLNA encoding filamin A cause this disease.","Congenital malformation"
"H01673","Palmoplantar keratoderma","Palmoplantar keratodermas (PPK) comprise a heterogeneous group of keratinization disorders with hyperkeratotic thickening of palms and soles. Sporadic or acquired forms of PPKs and hereditary forms exist. The causes of acquired PPK vary, and include exposure to certain chemicals, side effects of certain drugs, and metabolic disorders. There is as yet no cure for hereditary PPK. In patients with acquired PPK, the cause should be treated or eliminated, if possible. In both instances, optimized treatment can lead to a significant improvement in symptoms. Topical therapy with urea-based ointments improves the skin's absorption of moisture and has keratolytic effects. Topical vitamin D therapy is another option.","Skin and connective tissue disease"
"H00593","Limb-girdle muscular dystrophy","Limb-girdle muscular dystrophy (LGMD) is a heterogeneous group of inherited disorders characterized by progressive muscle weakness that begins from the proximal limb muscles. The disease is not congenital, with the age at onset of symptoms varying from early childhood to late adulthood. The primary distinction is between the autosomal dominant (LGMDD) and the autosomal recessive forms (LGMDR). According to the disease mechanisms, the LGMDs may be grouped as follows: dystrophin-dystroglycan complex defects, membrane defects, enzymatic, sarcomeric, and nuclear lamina.","Nervous system disease; Musculoskeletal disease"
"H01441","Pseudomonas aeruginosa infection","Pseudomonas aeruginosa is a leading cause of nosocomial bloodstream infections, ranking third among gram-negative bacteria, after Escherichia coli and Klebsiella species. Intrinsic resistance has been traditionally attributed to the low permeability of cellular envelopes together with the presence of chromosomally-encoded detoxification systems such as multidrug efflux pumps or antibiotic inactivating enzymes. Some strains acquire increased resistance via the horizontal transfer of resistance determinants and mutations in chromosomal genes.","Infectious disease"
"H01819","Early myoclonic encephalopathy","Early myoclonic encephalopathy (EME) is a rare malignant epileptic syndrome. The erratic myoclonus with or without focal motor seizures, onset before 3 months of age, and persistent suppression-burst pattern in electroencephalograph (EEG) are accepted as the diagnostic criteria for EME. The pathogenesis of EME is variable, with structural, metabolic, and genetic abnormalities all playing a role. Associated metabolic abnormalities are frequently described. In particular, nonketotic hyperglycinemia has been associated with a large number of cases. The prognosis of EME is poor, with no effective treatment, and children with the condition either die within 1-2 years after birth or survive in a persistent vegetative state.","Nervous system disease"
"H01025","Familial adenomatous polyposis","Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited disorder characterized by the early onset of hundreds to thousands of adenomas throughout in the rectum and colon. If left untreated, all patients with FAP develop colon cancer a decade after the appearance of the polyps. The genetic defect in FAP is a germline mutation in the adenomatous polyposis coli (APC) gene. In a subset of individuals, a MUTYH mutation causes a recessively inherited polyposis condition.","Gastrointestinal disease"
"H02492","Microcephaly, growth restriction, and increased sister chromatid exchange","Microcephaly, growth restriction, and increased sister chromatid exchange (MGRISCE) is characterized by prenatal onset growth restriction and microcephaly. Diagnostically, a hallmark feature is the presence of increased sister chromatid exchanges on cytogenetic testing. MGRISCE1, caused by biallelic mutations in BLM, is known as Bloom syndrome [DS:H01346]. Recently, MGRISCE2, caused by mutations in TOP3A, has been reported. TOP3A encodes topoisomerase III alpha, which binds to BLM as part of the BTRR complex, and promotes dissolution of double Holliday junctions arising during homologous recombination.","Congenital malformation"
"H01217","Primary localized cutaneous amyloidosis","Primary localized cutaneous amyloidosis (PLCA) is a chronic itchy skin disorder associated with amyloid deposits in the superficial dermis. It is a purely cutaneous disease with no association with systemic forms of amyloidosis. Clinically, skin lesions comprise small, flat-top papules (lichen amyloidosis) or brown-gray macules (macular amyloidosis). PLCA is relatively common in South America and Asia, and some cases have an autosomal dominant family history (familial PLCA, FPLCA). The genetic basis of FPLCA involves mutations in the OSMR and IL31RA genes. Both belong to the family of interleukin (IL)-6 family cytokine receptors.","Skin disease"
"H00558","Geroderma osteodysplasticum","Geroderma osteodysplasticum is a rare autosomal recessive disorder characterized by wrinkled skin and severe osteopenia with spontaneous fractures and the lack of large open fontanels. Mutations have been discovered in SCYL1BP1, which localizes to the Golgi apparatus and is expressed in skin and osteoblasts.","Congenital malformation"
"H02459","Syndromic neurodevelopmental disorder","Syndromic neurodevelopmental disorder (NED) is a group of disorder that have a number of clinical features in addition to intellectual disability and developmental delay. Many genes that cause these syndromes have been identified to date.","Nervous system disease"
"H00900","Geleophysic dysplasia","Geleophysic dysplasia is an autosomal recessive disorder resembling a lysosomal storage disorder. It is characterized by short stature, short hands and feet due to short, plump tubular bones, stiff joints, distinctive facial features, and progressive valvular cardiac disease.","Congenital malformation"
"H01228","Insulin-resistant diabetes mellitus with acanthosis nigricans","Insulin-resistant diabetes mellitus with acanthosis nigricans (IRAN) is an unusual cause of diabetes that result from metabolic abnormalities associated with mutations of the insulin receptor (INSR) gene, characterized by phenotypic description of extreme insulin resistance, acanthosis nigricans, and hyperandrogenism. Other phenotype of IRAN form includes hirsutism and polycystic ovarian disease in a patient who is usually not obese. There is no distinctive serum marker. Leprechaunism [DS:H00719] and the Rabson-Mendenhall syndrome [DS:H00942] also have mutations in INSR with subsequent alterations in insulin receptor function and extreme insulin resistance.","Metabolic disease; Endocrine disease"
"H01826","Mesial temporal lobe epilepsy with hippocampal sclerosis","Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is a group of chronic disorders characterized by prominent neuronal loss and gliosis in the hippocampus and amygdala. MTLE-HS is restricted to patients in whom hippocampal atrophy and/or abnormal signal intensity on MRI, anterior temporal interictal epileptiform discharges, and additional evidence of temporal dysfunction on functional images and neuro-psychological assessment are demonstrated.Patients with MTLE-HS often have a history of early risk factors such as febrile seizures, status epilepticus (SE) or infection. A seizure-free period may ensue before uncontrolled partial seizures begin. Epileptic focus is located deeply in the mesial temporal region including mainly hippocampus, parahippocampal gyrus and amygdala. The anatomopathological hallmark is sclerosis of the hippocampus. MTLE-HS is restricted to patients in whom hippocampal atrophy and/or abnormal signal intensity on MRI, anterior temporal interictal epileptiform discharges, and additional evidence of temporal dysfunction on functional images and neuro-psychological assessment are demonstrated. Since most of the cases are drug resistant, epilepsy surgery is the current gold standard therapy option for cessation of seizures. Familial forms of MTLE-HS have been recognized, but no causal gene has been identified so far.","Nervous system disease"
"H00763","Transient bullous dermolysis of the newborn","Transient bullous dermolysis of the newborn is a rare disorder in which subepidermal blistering presents at birth. Tissue separation occurs below the lamina densa, due to abnormal intraepidermal accumulation of type VII collagen. The disease usually regresses during early life, as type VII collagen secretion gradually recovers.","Congenital malformation"
"H02034","Central hypothyroidism and testicular enlargement","Central hypothyroidism and testicular enlargement is a novel X-linked disorder in which loss-of-function mutations in IGSF1. It causes central hypothyroidism, testis enlargement, and variable prolactin and growth hormone deficiency.","Endocrine disease"
"H02206","Aceruloplasminemia","Aceruloplasminemia is an autosomal recessive disorder associated with severe iron deposition in visceral organ and brain tissues. The clinical symptoms are progressive dementia, extrapyramidal disorders, cerebellar ataxia, and diabetes mellitus. The symptoms appear when patients are between 30 and 50 years old. Patients have serum ceruloplasmin deficiencies and increased serum ferritin concentrations. The genetic defects in the ceruloplasmin gene has been identified in the patients.","Nervous system disease"
"H01483","Acromegaly","Acromegaly (ACM) is a disorder characterized by increased circulating GH and IGF-I (a GH-induced liver protein) levels that is associated with significant morbidity and excess mortality. Patients with persistently elevated GH and IGF-I levels have an increased risk of multiple comorbidities, including left ventricular dysfunction, obstructive sleep apnea, arthritis, impaired glucose tolerance, and colonic polyps. Most cases of ACM occur as a result of a sporadic GH-secreting pituitary adenoma (PA). However, ACM can occur in a familial setting, either associated with other endocrine abnormalities or as an isolated disorder. Somatic activating mutations in the GNAS gene, which encodes for the Gs-alpha subunit of G-proteins, are found in up to 40% of sporadic GH-secreting PA. Familial ACM can occur in the context of rare inherited syndromes such as familial isolated pituitary adenoma (FIPA), which is caused in 15-20% of cases by aryl hydrocarbon receptor interacting protein (AIP) gene germline mutations. Moreover, a recurrent mutation was found in GPR101 in some patients with non-familial ACM.","Endocrine disease"
"H00551","Alagille syndrome","Alagille syndrome is a multi-system hereditary disorder characterized by hepatic bile duct paucity and cardiovascular malformations including pulmonic stenosis/ peripheral pulmonary stenosis and tetralogy of Fallot. Affected individuals show typical facies and abnormal butterfly vertebrae as well. Mutations in the Notch pathway cause Alagille syndrome.","Congenital malformation"
"H00909","Cleft palate with ankyloglossia","Cleft palate with ankyloglossia is an X-linked semi-dominant craniofacial disorder caused by mutations in the TBX22 transcription factor. It affects male patients and approximately one third of female carriers. It is resulted from failure of the palate to close and affected individuals will have problems with feeding, speech, hearing, and dentition.","Congenital malformation"
"H00135","Krabbe disease","Krabbe disease is an autosomal recessive disorder caused by deficient activity of galactosylceramidase.","Inherited metabolic disease; Lysosomal storage disease; Nervous system disease"
"H00307","Vibrio parahaemolyticus infection","Vibrio parahaemolyticus is a Gram-negative halophilic bacterium that naturally inhabits marine and estuarine environments. It is a well-recognized pathogen of both aquatic animals and humans. In the case of humans, it is often acquired through the consumption of raw or undercooked seafood, causing gastroenteritis with watery diarrhea.","Infectious disease"
"H02450","Horizontal gaze palsy with progressive scoliosis","Horizontal gaze palsy with progressive scoliosis (HGPPS) is an autosomal recessive disorder characterized by congenital absence of horizontal conjugate eye movements with progressive scoliosis developing in childhood and adolescence. HGPPS is caused by mutations in the axon guidance molecule ROBO3. Recently, it has been reported that mutations in DCC cause the syndrome with combined features of agenesis of the corpus callosum and HGPPS.","Nervous system disease"
"H01013","Adult i phenotype","Adult i phenotype is a rare autosomal recessive condition that was found to be highly associated with congenital cataract. The I and i antigens are carbohydrate structures on glycoproteins and glycolipids on the cell surface of a variety of tissues and body fluids. Most adult red blood cells (RBCs) abundantly express I antigen. Conversion of the i antigen into an I structure takes place during the first 18 months after birth as a result of the expression of a specific transferase, I-branching GCNT2. Lack of this enzyme results in the adult i phenotype.","Hematologic disease"
"H01221","Epithelial basement membrane corneal dystrophy","Epithelial basement membrane corneal dystrophy (EBMD) is a common bilateral epithelial dystrophy. There is usually no hereditary pattern, but some cases presented with an autosomal dominant inheritance. Mutations in the TGFBI/BIGH3 genes, which are known to cause various forms of corneal dystrophies, have been identified. Sheet-like areas of basement membrane originating from the basal epithelial cells of the corneal epithelium and extending superficially into the epithelium are the hallmarks of EBMD. Most patients are asymptomatic before the age of 30 years, but 10% of them may have recurrent idiopathic erosions and a loss of vision due to surface irregularity.","Nervous system disease"
"H01645","Hyperthyroidism","Hyperthyroidism is a pathological disorder characterised by increased thyroid hormone synthesis and secretion from the thyroid gland. The term thyrotoxicosis is not synonymous with hyperthyroidism. Thyrotoxicosis is defined as the clinical syndrome of hypermetabolism resulting from increased thyroid hormone levels, irrespective of the source. The causes of hyperthyroidism include Graves' disease, toxic multinodular goiter, and solitary toxic adenoma. Less common causes of hyperthyroidism include thyrotropin-induced thyrotoxicosis and trophoblastic tumours. The causes of thyrotoxicosis without hyperthyroidism are less common and generally transient. In patients with silent thyroiditis, post-partum thyroiditis, or subacute painful thyroiditis, the destruction of thyrocytes leads to release of preformed hormones into the circulation. Drug-induced thyrotoxicosis has the same pathogenic mechanism as thyroiditis. Exogenous thyrotoxicosis develops after ingestion of excessive amounts of thyroid hormone, and is associated with low serum thyroglobulin concentrations. Patients of hyperthyroidism/thyrotoxicosis usually have fatigue, nervousness or anxiety, weight loss, palpitations, and heat sensitivity. Clinical findings almost always include tachycardia, warm moist skin, the presence of an enlarged thyroid, and a slight tremor. The three options for treating patients with hyperthyroidism are antithyroid drugs (ATDs), radioactive iodine ablation, and surgery. All three therapeutic options would be effective in the treatment of patients with Graves' disease, whereas patients with toxic adenoma or toxic multinodular goiter should have either radioactive iodine therapy or surgery, since these patients rarely go into remission. In patients with toxic nodular goiter, ATDs are generally used to restore euthyroidism before definitive treatment with surgery or radioactive iodine, and infrequently used as long-term treatment when the other two therapies are contraindicated or the patient has a short life expectancy.","Endocrine disease"
"H00797","Martsolf syndrome","Martsolf syndrome is a rare autosomal recessive condition that shows symptoms similar to Warburg Micro syndrome. It is characterized by severe mental retardation, congenital cataract, microcephaly, bone and joint anomalies, and genital hypoplasia.","Congenital malformation"
"H01477","Congenital short bowel syndrome","Congenital short bowel syndrome (CSBS) is an inherited intestinal disorder occurring in newborns and infants. Affected babies typically present a shortened bowel (approximately 50 cm) compared with normal lenth rages from 190 to 280 cm. CSBS causes malabsorption and the most common symptoms including chronic diarrhea, vomiting and weight loss, thus leading to failure to thrive. Gene mutation in coxsakie and adenovirus receptor-like membrane protein (CLMP) has been reported to be associated with this disease.","Congenital malformation"
"H00338","Pseudomembranous colitis","Clostridium difficile is a gram-positive anaerobic bacillus that causes a broad spectrum of clinical symptoms ranging from mild diarrhea to severe pseudomembranous colitis. C. difficile can be transmitted by the fecal-oral route from person to person and instrument to patient.","Infectious disease"
"H00936","Goldberg-Shprintzen megacolon syndrome","Goldberg-Shprintzen megacolon syndrome is a rare disorder caused by inactivating mutations in the kinesin binding protein (KBP) and is characterized by central and enteric nervous system defects. Clinical features of this syndrome include polymicrogyria, mild mental retardation, microcephaly, facial dysmorphisms, and short-segment Hirschsprung disease. The precise function of KBP is largely unclear, but it is required for cell differentiation and neurite development.","Congenital malformation"
"H02239","Ehlers-Danlos syndrome, spondylodysplastic type","Ehlers-Danlos syndrome, spondylodysplastic type (EDSSPD) is a rare autosomal recessive connective tissue disorder, caused by biallelic B4GALT7, B3GALT6, and SLC39A13 mutations. The majority of EDSSPD patients presented with short stature, skin hyperextensibility, facial dysmorphisms, peculiar radiological findings, muscle hypotonia and joint laxity.","Congenital malformation"
"H01448","Hoarding disorder","Hoarding disorder is characterized by persistent difficulty discarding possessions, regardless of the value others may attribute to these possessions. They accumulate a large number of possessions that often fill up or clutter active living areas of the home or workplace to the extent that their intended use is no longer possible. Previously, hoarding has been treated as a typical obsessive-compulsive disorder (OCD) symptom, using first-line pharmacological and psychological treatments for OCD, however, the results have not been robust. Clinical trial evidence suggests that OCD patients with hoarding symptoms are less responsive to selective serotonin reuptake inhibitors (SSRIs) than those without hoarding symptoms. On the other hand, hoarding and non-hoarding OCD patients fared equally well in one open trial of paroxetine.","Mental and behavioural disorder"
"H01810","Congenital myopathy","The congenital myopathies are a group of genetic muscle disorders characterised clinically by hypotonia and weakness, usually from birth, and a static or slowly progressive clinical course. Congenital myopathies are mainly defined by the predominant histopathological features which include nemaline rods, central cores, multiple minicores, central nuclei, and selective hypotrophy of type 1 fibres. Based on these features, individual congenital myopathies such as nemaline myopathy, central core disease, multi-minicore disease, centronuclear myopathy, and congenital fiber type disproportion were reported. Over the past decade there have been major advances in defining the genetic basis of the majority of congenital myopathy subtypes. However the relationship between each congenital myopathy, defined on histological grounds, and the genetic cause is complex. Many of the congenital myopathies are due to mutations in more than one gene, and mutations in the same gene can cause different muscle pathologies.","Nervous system disease; Musculoskeletal disease"
"H01470","Giant cell tumor of bone","Giant-cell tumor of bone (GCTB) is a rare osteolytic tumor of the bone. Although classified as a benign tumor, GCTB is characterized by local aggressiveness and risk of local recurrence. Its name is derived from the numerous multinucleated giant cells found within the tumor, which are principally responsible for the extensive bone resorption that is characteristic of GCTB. However, the neoplastic components of GCTB are the spindle-like stromal cells, which produce RANKL that recruits monocytic osteoclast precursors from blood to the tumor, and stimulates differentiation into multinucleated giant cells. Recently, denosumab (RANKL inhibitor) has become a new treatment option for locally advanced GCTB.","Skeletal diseases"
"H01642","Renal anemia","Renal anemia is one of the most frequent complications of chronic kidney disease. Anemia leads to a decrease in oxygen delivery to vital organs, which is initially compensated for by tachycardia and cardiac hypertrophy, but eventually leads to the development of cardiovascular disease. Renal anemia is caused by the deficiency of endogenous erythropoietin (EPO) due to renal dysfunction. EPO is a glycoprotein hormone that has the role of the primary regulator of erythropoiesis. Formerly, treatment options were essentially limited to blood transfusions and androgen therapy, with its risks. However, since the late 1980s, the availability of recombinant human erythropoietin has revolutionized the management of renal anemia, and erythropoiesis-stimulating agents (ESAs) are now the mostly widely used drugs.","Urinary system disease"
"H00790","Keratosis linearis with ichthyosis congenita and sclerosing keratoderma","Keratosis linearis with ichthyosis congenita and sclerosing keratoderma (KLICK) syndrome is a rare combination of congenital ichthyosis, sclerosing palmoplantar keratoderma with pseudoainhum, and bizarre linear hyperkeratotic papules on the flexural side of large joints. There is no associated systemic involvement. The disease is inherited as an autosomal-recessive trait.","Congenital malformation"
"H01226","Polysyndactyly","Polysyndactyly, also known as preaxial polydactyly type IV, is a rare autosomal dominant limb malformation, caused by mutations in the GLI3 gene. It is comprising duplicated halluces, with syndactyly of preaxial toes, broad or duplicated thumbs, and syndactyly of the third and fourth fingers. GLI3 is regarded as a mediator of sonic hedgehog signaling regulating development at multiple sites such as the limbs, the lungs, and the brain.","Congenital malformation"
"H01828","Opsismodysplasia","Opsismodysplasia (OPS) is a rare, autosomal-recessive skeletal dysplasia primarily characterized by growth plate defects and delayed bone maturation. Its clinical features are rhizomelic micromelia and facial dysmorphism, including prominent brow, large fontanels, depressed nasal bridge, and small anteverted nose with long philtrum, as well as short feet and hands with sausage-like fingers. Death secondary to respiratory failure during the first few years of life was reported in the cases originally described but the outcome is now known to be highly variable with multiple long-term survivors. Typical radiographical features include short long bones with markedly delayed epiphyseal mineralization, metaphyseal cupping, short metacarpals and phalanges, and severe platyspondyly. Mutations in the gene encoding inositol polyphosphate phosphatase-like 1 (INPPL1) are found in several families with OPS. However, not all patients have INPPL1 variants suggesting that OPS exhibits genetic heterogeneity.","Congenital malformation"
"H01014","Sparganosis","Human sparganosis is caused by the larval form (spargana) of the canine/feline tapeworms belonging to the genus Spirometra. A wide range of amphibians, reptiles, birds, and mammals serve as second intermediate/paratenic hosts. Humans become infected by ingesting the raw or undercooked meat of snakes or frogs, drinking untreated water, or using raw flesh in traditional poultices. Sparganosis has been reported sporadically around the world, and a higher prevalence of the disease occurs in several Asian countries. Spargana invade the brain, eyes, spinal cord, breast, and subcutaneous tissues, leading to blindness, paralysis, and even death.","Infectious disease"
"H00300","Enterobacter infection","Enterobacter infections are commonly found in nosocomial settings and Enterobacter spp. have been recognized as increasingly important pathogens. They are intrinsically resistant to aminopenicillins, cefazolin, and cefoxitin because they produce constitutive chromosome AmpC beta-lactamase. Enterobacter spp. are recovered from the respiratory tract, surgical wounds, urinary tract, and blood and are implicated in a broad range of clinical syndromes.","Infectious disease"
"H02457","Developmental delay, leukoencephalopathy, and neurologic decompensation","Developmental delay, leukoencephalopathy, and neurologic decompensation is an autosomal dominant neurodevelopmental syndrome caused by missense mutations in EIF2AK1 and EIF2AK2. They encode members of the eIF-2-alpha kinase family that inhibits protein synthesis in response to physiologic stress conditions.","Nervous system disease"
"H00132","Mucopolysaccharidosis type VII","Mucopolysaccharidosis type VII (MPS7) is an autosomal recessive lysosomal storage disorder caused by deficient activity of beta-glucuronidase in glycosaminoglycan degradation. The enzyme defect results in the accumulation of heparan sulfate, dermatan sulfate, and chondroitin-4,6-sulfate occurs in many organs, as well as elevated metabolite levels in urine. This disorder is characterized by mental retardation, coarse faces, dysostosis multiplex, hepatosplenomegaly, and hydrops fetails.","Inherited metabolic disease; Lysosomal storage disease"
"H02201","Mitochondrial myopathy with lactic acidosis","Mitochondrial myopathy with lactic acidosis is an autosomal recessive metabolic myopathy associated with chronic lactic acidemia, growth failure, and nerve deafness. It has been reported that loss of function mutations in PNPLA8 encoding calcium-independent phospholipase A2 gamma cause this disease.","Congenital disorder of metabolism"
"H01484","5q- syndrome","5q- syndrome is a subtype of myelodysplastic syndrome (MDS) characterized by bone marrow erythroid hyperplasia, atypical megakaryocytes, thrombocythemia, refractory anemia, and low risk of progression to acute myeloid leukemia (AML) compared with other types of MDS. The WHO has proposed diagnostic criteria for the 5q- syndrome, defining the syndrome as representing de novo MDS, with a 5q interstitial deletion between bands 31 and 33 as the sole cytogenetic abnormality, macrocytic anemia, less than 5% blasts in the peripheral blood, and a normal or increased platelet count. The 5q- syndrome is also unique because it shows a remarkable response to treatment with the lenalidomide. It has been suggested that the 5q- syndrome is caused by haploinsufficiency of the ribosomal protein S14 (RPS14) gene which maps to the commonly deleted region.","Hematologic disease"
"H00556","CHARGE syndrome","CHARGE syndrome is a rare, usually sporadic disorder with multiple congenital anomalies. CHARGE is an acronym for the six prevalent clinical features of the disease, namely, coloboma, heart defect, atresia of choanae, retardation of growth and development, genital hypoplasia, and ear anomalies/deafness. Abnormal semicircular canals, arhinencephaly, and rhombencephalic dysfunctions are also considered as important features. Nearly 2/3 of cases harbor mutations within the CHD7 gene.","Congenital malformation"
"H00764","Chromosme 5p deletion syndrome","The Cri du Chat syndrome (CdCS) is a genetic disease resulting from a deletion of variable size occurring on the short arm of chromosome 5. The main clinical features are a high-pitched monochromatic cry, microcephaly, broad nasal bridge, epicanthal folds, micrognathia, abnormal dermatoglyphics, and severe psychomotor and mental retardation. SEMAF/ SEMA5A and CTNND2 have been mapped to the critical regions, and their deletion may be associated with mental retardation in CdCS patients. The TERT deletion may contribute to the phenotypic changes in CdCS.","Chromosomal abnormality"
"H02033","Mucormycosis","The class Zygomycetes is divided into two orders, Mucorales and Entomophthorales. These two orders produce dramatically different infections. Genera from the order Mucorales cause an angioinvasive infection called mucormycosis. Infection sites include the lungs, rhinocerebral spaces, sinuses, soft tissue, skin, gastrointestinal tract and bloodstream. Genera from the order Entomophthorales produce a chronic subcutaneous infection called entomophthoramycosis in immunocompetent patients.","Infectious disease"
"H01817","Beukes hip dysplasia","Beukes hip dysplasia (BHD) is an autosomal dominant disorder characterised by bilateral dysmorphism of the proximal femur, which results in severe degenerative osteoarthropathy. Pain develops in the hip joints in early childhood in the majority of affected persons and the course is progressive with severe crippling by early adulthood. General health is good, and height is not significantly reduced. The condition is unique in that the underlying dysplasia and subsequent osteoarthritis are confined to the hip joint. Identification of a mutation in the ubiquitin-fold modifier 1-specific peptidase 2 gene, UFSP2 has been reported.","Congenital malformation"
"H01219","Restrictive cardiomyopathy","Restrictive cardiomyopathy (RCM) is an uncommon heart muscle disorder characterized by impaired ventricular filling and increased stiffness of the myocardium with diastolic dysfunction, resulting in atrial enlargement and elevated systemic and pulmonary venous pressure. To date, mutations have been identified in the cardiac genes for desmin, alpha-actin, troponin I and troponin T.","Cardiovascular disease"
"H01689","Fisher syndrome","Fisher syndrome is a variant of the Guillain- Barre syndrome (GBS) and its classical clinical triad consists of ophthalmoplegia, ataxia, and areflexia. It is a relatively rare neurological disorder, accounting for approximately 5% of acute inflammatory polyneuropathies. This disease is an immune-mediated condition and specific anti-ganglioside antibodies, especially IgG anti-GQ1b antibodies, are found in over 80% of the patients. Campylobacter and Haemophilus influenzae have been reported as infectious agents prior to the onset of Fisher syndrome. It has been reported that the median period required for the disappearance of ataxia was about 1 month, without therapy.","Immune system disease; Nervous system disease"
"H00569","Aarskog-Scott syndrome","Aarskog-Scott syndrome (AAS) is an X-linked disorder characterized by craniofacial, skeletal, and urogenital malformations and short stature. Mutations in the only known causative gene FGD1 are found in about one-fifth of the cases with the clinical diagnosis of AAS.","Congenital malformation"
"H00931","Growth hormone insensitivity with immunodeficiency","Growth hormone insensitivity with immunodeficiency is a combined phenotype of growth hormone insensitivity that resembles Laron syndrome and immunodeficiency. Homozygous inactivating mutation in the STAT5b, a component of the GH signaling pathway, leads to a complete absence of protein expression.","Musculoskeletal disease; Primary immunodeficiency"
"H02468","Early childhood-onset progressive leukodystrophy","Early childhood-onset progressive leukodystrophy (PLDECO) is a rare autosomal recessive disorder caused by deficiency of the alkaline ceramidase. Mutations in the ACER3 gene result in inactivation of ACER3, leading to the accumulation of various sphingolipids in blood and probably in brain.","Congenital disorder of metabolism"
"H01880","Autosomal recessive microcephaly and chorioretinopathy","Autosomal-recessive microcephaly and chorioretinopathy (MCCRP) is a rare developmental disorder characterized by primary microcephaly, delayed psychomotor development, growth retardation with dwarfism, and visual impairment. In MCCRP, microcephaly ranges from mild to severe and has variable impact on cognitive performance, ranging from moderate developmental delay to normal intelligence. The features of the visual impairment in MCCRP patients are variable, but the chorioretinopathy is a constant feature and includes typical punched-out lesions that can severely impair vision and occasional retinal folds that can progress to retinal detachment. To date, three responsible genes have been described.","Congenital malformation"
"H00952","Thiel-Behnke dystrophies","Thiel-Behnke dystrophy (TBCD) is an autosomal dominant dystrophy with recurrent corneal erosions developing in the first and second decade of life. TBCD shares many similarities with Reis-Bucklers corneal dystrophy (RBCD), but decreasing visual acuity is seen later than with RBCD. Electron microscopy reveals curly fibers deposited in Bowman's layer and this finding differentiates it from RBCD. Both TBCD and RBCD are linked to mutations in the TGFBI gene. TBCD is also linked to a mutation on chromosome 10q23-24, the gene product is currently unknown.","Nervous system disease"
"H00738","Ichthyosis with confetti","Ichthyosis with confetti (IWC) is a rare and severe skin disease characterized by erythroderma, prominent scaling, and palmoplantar keratoderma. Patients develop numerous pale confetti-like white patches on red skin.","Congenital malformation"
"H01874","Cronkhite-Canada syndrome","Cronkhite-Canada syndrome (CCS) is a rare noninherited condition characterized by gastrointestinal hamartomatous polyposis, alopecia, onychodystrophy, hyperpigmentation, and diarrhea. CCS is reported worldwide, with 75% of cases in Japan. The average age of onset is 60 years and the male to female ratio is 3:2. At present, the pathogenesis of CCS is unknown, but the factors that include immune abnormalities, infection, and allergies, may be relevant. There are no evidence-based therapies. Numerous treatments have been attempted in CCS patients, with varying degrees of success. These treatments include glucocorticoids, nutritional support, antibiotics, and polypectomy.","Gastrointestinal disease"
"H01048","Liver fluke disease","Fascioliasis is a foodborne zoonotic disease caused by the liver flukes Fasciola hepatica and Fasciola gigantica. Whereas in Europe, the Americas and Oceania only F. hepatica is concerned, the distributions of both species overlap in many areas of Africa and Asia. An infection is accomplished through oral ingestion of the infective stage of the parasite either through consumption of uncooked or unwashed aquatic plants, or through drinking contaminated water. The presence of F. hepatica flukes in humans was first documented in 1760.","Infectious disease"
"H02262","PEBEL","Early-onset progressive encephalopathy with brain edema and leukoencephalopathy (PEBEL) is an autosomal recessive infancy-onset disease characterized by ataxia, cerebellar edema, spinal myelopathy, and skin lesions. It is induced by febrile infections, leading to coma and finally to death within the first 3 years of life. NAXE mutations disrupt the cellular NAD(P)HX repair system and cause PEBEL.","Nervous system disease"
"H00535","Lymphatic malformation","Lymphatic malformation (LMPHM), formerly known as hereditary lymphedema (LMPH), is a form of generalized lymphatic dysplasia characterized by chronic lesions of the extremities due to insufficient lymphatic drainage. The dilated lymphatic channels that are not connected to the lymphatic vessels cause these edemas.","Congenital malformation"
"H00707","Ichthyosis hystrix, Curth-Macklin type","Ichthyosis hystrix, Curth-Macklin type is a rare autosomal dominant skin disorder characterized by spiky, verrucous hyperkeratosis of palms and soles. Diagnosis is supported by specific ultrastructural abnormalities such as perinuclear tonofibril shells of keratin intermediate filaments in binucleated suprabasal keratinocytes.","Congenital malformation"
"H02050","Prepubertal periodontitis","Prepubertal periodontitis (PPP) is a rare and rapidly progressive disease of young children that results in destruction of the periodontal support of the primary dentition. Both autosomal dominant and recessive forms transmission have been reported for PPP. Mutations in cathepsin C gene cause this disease.","Digestive system disease"
"H00363","Candidiasis","Candidiasis is a fungal infection with Candida species, predominantly with Candida albicans. Invasive candidiasis is a major cause of morbidity and mortality in the intensive care unit (ICU) setting, causing bloodstream infections. Recently, various non-C. albicans species have emerged as infecting agents. In patients with impaired IL-17 immunity, recurrent or persistent infections are observed (chronic mucocutaneous candidiasis disease).","Infectious disease"
"H02434","Diffuse large B-cell lymphoma, not otherwise specified","Diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS) is the most common type of DLBCL. DLBCL accounts for 30-40% of all non-Hodgkin lymphomas (NHL), making it the most prevalent form of NHL. DLBCL can occur as primary disease or through histologic transformation from other low-grade B-cell lymphoma, and is a clinically and genetically heterogeneous disease. The cell-of-origin (COO) determination based on gene expression profiling (GEP) subdivides most DLBCL, NOS patients into two main categories, namely germinal center B-cell-like (GCB) and activated B-cell-like (ABC) DLBCL. GCB subtype is characterized by frequent mutations in involved histone methylation or acetylation (EZH2, EP300), B-cell homing (GNA13, GNAI2), PI3K pathway signalling (PTEN), and apoptotic pathway (BCL2). In contrast, ABC subtype is driven by frequent mutations in the B cell receptor and NFKB pathways (CARD11, CD79a/CD79b, TNFAIP3 and MYD88).","Cancer"
"H01083","Bordetella bronchiseptica infection","Bordetella bronchiseptica is a common pathogen among dogs and pigs, but has rarely been implicated in human infections. Human infections caused by B. bronchiseptica occur mostly in immunocompromised patients and often present as pneumonia.","Infectious disease"
"H00151","Cerebrotendinous xanthomatosis","Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive lipid-storage disorder caused by deficient activity of CYP27A1 and characterized by formation of xanthomatous lesions in many tissues, particularly the brain, the lens of the eye, and tendons.","Inherited metabolic disease; Connective tissue disease"
"H01245","Immunodeficiency without anhidrotic ectodermal dysplasia","A NEMO mutant causing immunodeficiency without any sign of anhidrotic ectodermal dysplasia (EDA) has been identified. The mutation, which altered the exon 9 splice site, was present in cells of ectodermal and hematopoietic origin and resulted in a heterogeneous mixture of mutant and wild-type cDNA species.","Primary immunodeficiency"
"H00397","Ross River fever","Ross River fever is an infectious disease caused by Ross River virus (RRV), an alphavirus in the Togaviridae family of +ssRNA viruses, and transmitted by Aedes and Culex mosquitoes. RRV was first isolated in 1972 near Ross River in North Queensland, Australia.","Infectious disease"
"H00999","Coenzyme Q10 deficiency","Coenzyme Q10 deficiency is an autosomal recessive disorder with variable manifestations, including pure myopathy, myopathy with encephalopathy, cerebellar atrophy with ataxia, and infantile multisystem disease including encephalopathy and nephropathy. It has been shown that mutations in some genes involved in CoQ10 biosynthesis cause primary CoQ10 deficiency.","Nervous system disease"
"H01077","Bordetella hinzii infection","Bordetella hinzii is a recently added species to the genus Bordetella that is isolated from poultry with respiratory disease. B. hinzii is a potential human pathogen in immunocompromised patients or patients with underlying disease.","Infectious disease"
"H02296","Basan syndrome","Basan syndrome is a rare autosomal dominant ectodermal dysplasia, characterized by rapidly healing congenital acral bullae, congenital milia and lack of fingerprints. Other phenotypes include contractures of digits, hypohidrosis, palmoplantar keratoderma, and nail dystrophy. A mutation in the SMARCAD1 gene was recently reported to cause Basan syndrome.","Congenital malformation"
"H01413","Adams-Oliver syndrome","Adams-Oliver syndrome (AOS) is a rare condition defined by the combination of aplasia cutis congenita (ACC), characterized by scalp and skull lesions, and transverse limb abnormalities. Mutations in ARHGAP31 (AOS1), RBPJ (AOS3) and NOTCH1 (AOS5) cause autosomal dominant AOS. Mutations in DOCK6 (AOS2) and EOGT (AOS4) result in autosomal recessive AOS.","Congenital malformation"
"H01621","Pulmonary arterial hypertension","Pulmonary arterial hypertension (PAH) is a progressive disorder in which endothelial dysfunction and vascular remodeling obstruct small pulmonary arteries, resulting in increased pulmonary vascular resistance and pulmonary pressures. This leads to reduced cardiac output, right heart failure, and ultimately death. PAH is divided into disease subgroups that include heritable (HPAH, formerly familial PAH), idiopathic (IPAH), and PAH associated with a variety of other systemic diseases or drug/toxin exposures. It has been discovered that altered BMPR2 signaling is the major heritable risk factor for development of PAH, via rare variants (mutations) in the BMPR2 gene (coding for a type II receptor member of the transforming growth factor [TGF]-beta family). Pathogenic mutations in the type I receptor ACVRL1 and, at a significantly lower frequency, the type III receptor endoglin in multiple kindreds cause PAH associated with hereditary hemorrhagic telangiectasia (HHT). Together, these observations support a prominent role for TGF-beta family members in the development of PAH.","Cardiovascular disease"
"H01873","Obliterative bronchiolitis","Obliterative bronchiolitis (OB), also known as bronchiolitis obliterans, is a rare but serious condition resulting in progressive and irreversible airway obstruction. This disease is the result of injury to the respiratory and terminal bronchioles from a wide variety of potential causes. Although the pathogenesis of OB remains poorly understood, it seems clear that a multifaceted process of inflammation and resultant fibrotic transition occurs, resulting in airflow limitation and development of disease. Although OB has been described in all age groups, the frequency of underlying causes and potential prognoses are different for children and adults. For example, OB in children is most often seen following a severe lower-respiratory-tract infection, usually of adenovirus, whereas OB in adults is more commonly associated with occupational inhalation injuries, hypersensitivity pneumonitis, and autoimmune disorders. In lung transplant recipients, bronchiolitis obliterans syndrome is the major cause of death after the first year of transplantation and is a form of allograft rejection. There is no uniformly accepted treatment protocol for patients with OB. Many patients are tried on corticosteroids or other immunosuppressants based on anecdotal evidence of improvement. However, these medications have significant toxicity.","Respiratory disease"
"H01619","Primary pulmonary hypertension","Primary pulmonary hypertension (PPH) is a progressive disease characterised by raised pulmonary vascular resistance, which results in diminished right-heart function due to increased right ventricular afterload. PPH occurs most commonly in young and middle-aged women; mean survival from onset of symptoms is 2-3 years. Mutations in the type II bone morphogenetic protein (BMP) receptor (BMPR)-II are now considered to be the genetic basis for familial PPH and ~30% of cases of sporadic PPH. BMPs are members of the transforming growth factor beta superfamily and affect intracellular signalling via Smads and mitogen-activated protein kinases. It has been shown that missense mutations of cysteine residues in the extracellular or kinase domain of BMPR2 result in intracellular localisation of the mutated receptor and negligible Smad signalling.","Cardiovascular disease"
"H02068","Hypochondroplasia","Hypochondroplasia is an autosomal dominant skeletal dysplasia with rhizomelic short stature. Skeletal features are similar to but milder than those seen in achondroplasia. Mutations in fibroblast growth factor receptor (FGFR3) cause hypochondroplasia.","Congenital malformation"
"H01289","Mulibrey nanism","Mulibrey nanism is an autosomal recessive growth disorder characterized by prenatal-onset growth failure and heart disease involving constrictive pericarditis and restrictive cardiomyopathy. Mutations in the TRIM37 gene have been reported in Mulibrey nanism patients.","Congenital malformation"
"H01887","3MC syndrome","3MC syndrome is an autosomal recessive heterogeneous disorder with features linked to developmental abnormalities. Patients with 3MC syndrome may exhibit a spectrum of developmental features, including developmental delay, growth and mental retardation, and characteristic facial dysmorphism, such as hypertelorism, telecanthus, blepharophimosis, blepharoptosis, and epicanthus inversus. 3MC syndrome was originally described as four separate disorders: Malpuech syndrome, Carnevale syndrome, Michels syndrome, and Mingarelli syndrome. There is considerable overlap between them, which have similarities in facial appearance, leading to the suggestion that they should all be considered part of the same phenotypic spectrum known as 3MC syndrome. Mutations in lectin complement pathway genes have been reported to cause 3MC syndrome.","Congenital malformation"
"H00955","Granular corneal dystrophies","Granular dystrophy (GCD), inherited in an autosomal dominant fasion, is one of the most common corneal dystrophies characterized by the deposition of gray-white crumb like opacities in the anterior stroma that slowly increase in number and progress into deeper parts of the cornea. The disease is typically asymptomatic, but can present with pain from recurrent erosions and decreased vision. Opacities in granular dystrophy are composed of eosinophilic hyaline deposits. Differences in the clinical appearance of the discrete corneal opacities permit to divide into types of GCD; Type I classic form of GCD, type II Avellino or granular-lattice type, and type III Reis-Bucklers type. GCD has been linked to several mutations in TGFBI gene.","Nervous system disease"
"H00169","Ocular albinism","Ocular albinism type I is an X-linked disorder characterized by reduced visual acuity, photophobia, nystagmus, translucent irides, strabismus, hypermetropic refractive errors. Waardenburg syndrome type II is an autosomal recessive ocular albinism.","Inherited metabolic disease; Eye disease"
"H01626","Arteriosclerosis obliterans","Arteriosclerosis obliterans (ASO) is one of the most common peripheral vascular diseases that causes ischemic symptoms of the lower limbs. Symptoms include discomfort, numbness, intermittent claudication, or even gangrene and ulceration. The risk factors of ASO include age, male gender, smoking, hypertension, hyperlipidemia, diabetes mellitus, chronic renal failure, and hyperhomocysteinemia. There are no definitive treatments for ASO. The efficacy of surgical treatment is not satisfactory, and medication is required to maintain the postoperative vascular patency. In order to relieve symptoms such as cold sensation and intermittent claudication, drug therapy such as antiplatelet therapy and vasodilatory drugs are useful in the treatment of some patients with ASO. Adsorption of low-density lipoprotein (LDL) has also been applied for the treatment of ASO. At present, the diagnosis of ASO depends on several clinical tests, such as angiography, estimations of ankle/brachial index (ABI), and pulse-wave velocity (PWV), as well as the measurement of circulating hs-CRP levels. However, these examinations can only be detectable when ASO already developed, and there was no predictable markers for ASO in its earlier stages. Recent studies have reported that some micro RNAs could be serum markers for early-stage ASO.","Vascular disease"
"H02291","Retinal dystrophy, iris coloboma, and comedogenic acne syndrome","Retinal dystrophy, iris coloboma, and comedogenic acne syndrome (RDCCAS) is an early onset, progressive, and severe autosomal recessive retinitis pigmentosa. It is characterized by developmental abnormalities including patent ductus arteriosus and chorioretinal and iris colobomas. Some developed severe acne. In addition, the patients exhibited severe vitamin A deficiency, and diminished serum retinol levels. A homozygous splice site variant in the gene encoding retinol binding protein (RBP4) has been identified. RBP4 is the carrier of retinol in human plasma and is involved in transport of retinol from liver to peripheral tissue including the retina.","Nervous system disease"
"H01414","Hafnia alvei infection","The genus Hafnia, a member of the family Enterobacteriaceae, is occasionally implicated in both intestinal and extraintestinal infections in humans. Hafnia alvei is a facultative anaerobic opportunistic pathogen that is also known to play a role in microbial food spoilage. This species has been isolated from a wide range of nosocomial infections, including septicaemia, as well as respiratory, enteric, and urinary tract infections.","Infectious disease"
"H01070","Vibrio furnissii infection","Vibrio furnissii, first described as a gasproducing biovar of V. fluvialis, is associated with human acute gastroenteritis. The pathology of V. furnissii in gastroenteritis is potentially related to hemolysin production. A protein with multifaceted functions in solute binding, in in vitro hemolysis, in antibiotic resistance, and as a virulence factor in bacterial pathogenesis has been identified.","Infectious disease"
"H01242","Saccharopinuria","Saccharopinuria is a metabolic disorder caused by a defect in a bifunctional protein with lysine-ketoglutarate reductase (LKR) activity and saccharopine dehydrogenase (SDH) activity, aminoadipic semialdehyde synthase (AASS), which catalyzes the first two steps in the lysine-degradation pathway. Patients with this disorder have both hyperlysinemia and saccharopinuria, although the saccharopinuria is much more severe. It seems likely that this disorder results from specific mutations in the portion of AASS encoding SDH, which could explain the high levels of saccharopine, compared with that in patients with hyperlysinemia [DS:H00188].","Inherited metabolic disease"
"H00390","Hantavirus pulmonary syndrome","Hantavirus pulmonary syndrome is an often fatal infectious disease caused by orthohantaviruses in the order Bunyavirales of -ssRNA viruses. Rodents have long been considered to be the primary reservoir hosts of hantaviruses. However, recent discoveries have revealed that hantaviruses infect a more diverse range of mammalian hosts, particularly Chiroptera and Soricomorpha.","Infectious disease"
"H01084","Bordetella holmesii infection","Bordetella holmesii is a fastidious asaccharolytic oxidase-negative gram-negative bacterium closely related to B. pertussis. It has been reported as a rare cause of bacteremia, pertussis-like respiratory tract infection, and endocarditis predominantly in patients with anatomical or functional asplenia.","Infectious disease"
"H00156","Hyperlipoproteinemia, type III","Hyperlipoproteinemia type III is an autosomal recessively disorder characterized by the accumulation of intermediate-density lipoprotein due to mutation of apolipoprotein E.","Inherited metabolic disease; Cardiovascular disease"
"H00364","Cryptococcosis","Cryptococcus is a pathogenic yeast that causes opportunistic infection, especially in the immunocompromised patient. It mainly infects the central nervous system and causes meningitis. Cryptococcal lung disease is also an important clinical outcome, leading to severe pneumonia with respiratory failure.","Infectious disease"
"H02433","Hypomyelination with brainstem and spinal cord involvement and leg spasticity","Hypomyelination with brainstem and spinal cord involvement and leg spasticity (HBSL) is characterized by focal cerebral white matter abnormalities and spinal cord signal abnormalities. HBSL is the result of mutations in DARS, a cytoplasmic tRNA synthetase gene.","Congenital disorder of metabolism"
"H00700","Centronuclear myopathy","Centronuclear myopathy (CNM) is an inherited neuromuscular disorder defined by numerous centrally placed nuclei on muscle biopsy and clinical features of a congenital myopathy. CNM exists in the genetic bases of the three main forms: the X-linked recessive form or myotubular myopathy (XLMTM) with severe neonatal phenotype, caused by mutations in the MTM1 gene; the classical autosomal dominant (AD) forms with mild, moderate or severe phenotypes caused by mutations in the DNM2 gene; and an autosomal recessive (AR) form presenting severe and moderate phenotypes caused by mutations in the BIN1 gene. Recently, heterozygous MYF6 mutation is reported to be associated with CNM.","Nervous system disease; Musculoskeletal disease"
"H02057","Rotor syndrome","Rotor syndrome is an autosomal recessive disorder characterized by conjugated hyperbilirubinemia, coproporphyrinuria, and near-absent hepatic uptake of anionic diagnostics. It is linked to mutations predicted to cause complete deficiencies of the organic anion transporting polypeptides OATP1B1 and OATP1B3.","Congenital disorder of metabolism"
"H02265","Annular epidermolytic ichthyosis","Annular epidermolytic ichthyosis (AEI), also known as cyclic ichthyosis with epidermolytic hyperkeratosis (CIEHK), is a rare phenotypic variant of bullous congenital ichthyosiform erythroderma. AEI is an autosomal dominant disorder characterized by intermittent development of polycyclic, erythematous, scaly plaques on the trunk and proximal extremities. Mutations in keratin 10 or 1 have been identified in AEI.","Congenital malformation"
"H00532","Parkes Weber syndrome","Parkes Weber syndrome (PWS) is characterized by a large cutaneous vascular stain with multiple underlying subcutaneous and intramuscular arteriovenous fistulas (AVF), and overgrowth of the affected extremity. It has been reported that PWS is caused by RASA1 mutations.","Developmental disorder; Vascular disease"
"H02298","Macrocephaly, dysmorphic facies, and psychomotor retardation","Macrocephaly, dysmorphic facies, and psychomotor retardation (MDFPMR) is a rare autosomal recessive overgrowth syndrome. HERC1 mutations in individuals with MDFPMR have been reported. HERC1 is believed to be involved in intracellular membrane trafficking and ubiquitinization. It is also presumed to play a regulatory role in the mTOR pathway.","Congenital malformation"
"H00399","Avian influenza","Avian influenza is an infectious disease caused by Influenzavirus A that belongs to the genus Alphainfluenzavirus in the Orthomyxoviridae family of -ssRNA virus. Influenzavirus A viruses are species specific and rarely cross the species barrier. However, subtypes H5, H7, and H9 have caused sporadic infections in humans, mostly as a result of direct contact with infected birds. H5N1 high pathogenicity avian influenza virus causes a rapid onset of severe viral pneumonia and is highly fatal.","Infectious disease"
"H00997","CATSHL syndrome","CATSHL syndrome is characterised by camptodactyly, tall stature, scoliosis, and hearing loss. The syndrome is caused by a missense mutation in the FGFR3 gene. FGFR3 is a negative regulator of bone growth, and its mutations are well known to cause a variety of short-limbed bone dysplasias and craniosynostosis syndromes. The finding of CATSHL syndrome indicates that abnormal FGFR3 signaling can cause human anomalies by promoting as well as inhibiting endochondral bone growth.","Congenital malformation"
"H01845","Catel-Manzke syndrome","Catel-Manzke syndrome is a rare autosomal recessive disorder characterized by Pierre Robin sequence and a unique form of bilateral hyperphalangy causing clinodactyly of the index finger. Pierre Robin sequence is defined by micrognathia, obstruction of the airways due to a backward displacement of the tongue base, and, often but not always, cleft palate. Cardiac abnormalities, facial dysmorphisms, and additional skeletal abnormalities have also been described in a subset of patients with Catel-Manzke syndrome. Recently, homozygous or compound heterozygous pathogenic variants in TGDS have been discovered to cause Catel-Manzke syndrome.","Congenital malformation"
"H01079","3-Phosphoglycerate dehydrogenase (3-PGDH) deficiency","3-Phosphoglycerate dehydrogenase (3-PGDH) deficiency is a rare autosomal recessive disorder caused by a defect in the synthesis of the amino acid L-serine characterized clinically by congenital microcephaly, psychomotor retardation, and infantile onset of intractable seizures. The biochemical abnormalities associated with this disorder are low concentrations of L-serine, D-serine, and glycine in cerebrospinal fluid (CSF) and plasma. Mutations have been identified in PHGDH, the gene encoding 3-PGDH.","Inherited metabolic disease"
"H00963","Congenital hereditary endothelial dystrophy","Congenital hereditary endothelial dystrophy (CHED) is a rare inheritable disorder of the corneal endothelium characterized by bilateral symmetric corneal clouding (edema) with varied severity from mild opacification to milky, ground-glass opacification without other anterior segment abnormalities, usually evident at birth or in the early years of life. Two subtypes of CHED based on differences in the mode of inheritance are known, an autosomal dominant (CHED1) and an autosomal recessive (CHED2) type. Clinically, both forms of the disorder are similar; the distinction between them is made by the age at onset and the presence or absence of associated symptoms. Both CHED1 and CHED2 have been mapped to chromosome 20. The Solute Carrier family 4 (sodium borate cotransporter) member 11 (SLC4A11) has been identified as the candidate gene for CHED2. Mutations in SLC4A11 are described in Harboyan syndrome, which is characterized as CHED2 with hearing loss. Most patients with CHED have severe visual impairment and often require penetrating keratoplasty.","Nervous system disease"
"H00709","Birk Barel mental retardation syndrome (BBMRS)","Birk Barel mental retardation syndrome (BBMRS) is characterized by mental retardation, hypotonia, hyperactivity, and facial dysmorphism. The potassium channel KCNK9 gene, which is responsible for the disease, was found to be imprinted.","Congenital malformation"
"H00194","Lesch-Nyhan syndrome","Deficiency of hypoxanthine-guanine phosphoribosyltransferase activity is an inborn error of purine metabolism characterized by hyperuricemia with hyperuricosuria and a continuum spectrum of neurological manifestations.","Inherited metabolic disease; Nervous system disease"
"H01046","Trichuriasis","Trichuriasis is a parasitic disease caused by the whipworm Trichuris trichiura, which is prevalent, particularly in tropical and subtropical areas. The infections occur by ingestion of embryonated eggs through contaminated soil or food. Adult trichuris whipworms live in the large intestine (caecum and colon) and cause chronic dysentery and/or rectal prolapse.","Infectious disease"
"H01274","Growth delay due to insulin-like growth factor I resistance","Growth delay due to IGF-I resistance is characterised by variable prenatal and postnatal growth retardation and elevated serum IGF-I levels. It has been described that the defects in the IGF-IR gene cause postnatal growth failure.","Endocrine disease"
"H02095","Perrault syndrome","Perrault syndrome is a genetically and clinically heterogeneous autosomal-recessive condition characterized by sensorineural hearing loss and ovarian failure. Previously mutations have been described in different genes, mostly related to mitochondrial proteostasis.","Congenital malformation"
"H01610","Clonorchiasis","Clonorchiasis is an infectious disease of the biliary passages caused by Clonorchis sinensis of the family Opisthorchiidae. Clonorchis sinensis, the most common human liver fluke, is endemic in East Asia. The human and animal reservoir hosts acquire the infection from the ingestion of raw fish (the second intermediate hosts) containing infectious metacercariae.","Infectious disease"
"H01422","Carbapenem-resistant bacterial infection","Carbapenems [DG:DG01458] are a class of beta-lactam antibiotics often used as the last resort treatment for severe bacterial infections. Thus, the appearance of carbapenem resistance caused by acquisition of carbapenem-hydrolyzing beta-lactamases (carbapenemases), especially among Enterobacteriaceae, Pseudomonas and Acinetobacter, is considered as a global health threat.","Infectious disease"
"H02061","Estrogen resistance syndrome","Estrogen resistance syndrome is a rare, genetic endocrine disease, characterized by estrogen-receptor (ESR) insensitivity to estrogens. A few patients who has mutations in ESR1 gene has been reported. An adult male who was tall and had incomplete epiphyseal closure, and a young woman with delayed puberty have been described.","Endocrine and metabolic disease"
"H00736","Dorfman-Chanarin syndrome","Chanarin-Dorfman syndrome, also referred to as neutral-lipid-storage disease with ichthyosis, is a rare autosomal recessive disease of lipid metabolism. Cutaneous finding is congenital, generalized ichthyosis similar to that of non-bullous congenital ichthyosiform erythroderma. Other characteristics include hepatomegaly, sensorineural deafness, mental retardation, and cataracts. Mutations in the CGI-58 gene encoding a protein of the alpha/beta hydrolase domain subfamily are responsible for this disorder.","Congenital disorder of metabolism"
"H00504","Rubinstein-Taybi syndrome","Rubinstein-Taybi syndrome is an autosomal dominant disorder with distinctive facial features, broad thumbs and toes, and mental retardation. Mutations in CREBBP and EP300 have been reported in the syndrome.","Congenital malformation"
"H02253","Beaulieu-Boycott-Innes syndrome","Beaulieu-Boycott-Innes syndrome (BBIS) is a rare autosomal recessive neurodevelopmental disorder with intellectual disability associated with mutations in THOC6. The clinical presentation includes moderate to severe intellectual disability, mild microcephaly, and non-life threatening congenital malformations including cardiac septal defects, structural renal anomalies, cryptorchidism in males, submucous cleft palate, and corpus callosum dysgenesis. THOC6 is a part of the THO complex, which is involved in coordinating mRNA processing with export.","Congenital marformation"
"H00160","Abetalipoproteinemia","Abetalipoproteinemia is an autosomal recessive disorder of lipid metabolism caused by mutation of MTTP gene involved in the transport of lipids and required in the secretion of beta-lipoproteins.","Inherited metabolic disease"
"H02405","Oesophagostomiasis","Oesophagostomiasis is an infectious disease normally caused by Oesophagostomum bifurcum. Oesophagostomum bifurcum is highly and focally endemic in northern Ghana and Togo. Oesophagostomum species in man were first found in 1905 in southern Ethiopia.","Infectious disease"
"H00352","Whipple disease","Whipple disease (WD) is a rare chronic multi-system disease associated with the bacterium Tropheryma whipplei that is ubiquitously present in the environment. The clinical features of WD are non-specific and histological lesions in gastrointestinal system can be the major manifestations. Patients without symptoms of gastrointestinal disease might be insufficiently treated, resulting in a potentially fatal outcome such as endocarditis, neurological infection, osteoarticular infection, or uveitis.","Infectious disease"
"H01280","L-2-hydroxyglutaric aciduria","L-2-hydroxyglutaric aciduria (L2HGA) is a rare autosomal recessive neurometabolic disorder characterized by progressive ataxia, mental deficiency with subcortical leukoencephalopathy, and cerebellar atrophy.","Inherited metabolic disease"
"H02059","Leptin deficiency","Congenital leptin deficiency is a rare human genetic syndrome resulting in severe hyperphagia and early-onset obesity. Beneficial effects of leptin replacement therapy in this condition has been reported.","Endocrine and metabolic disease"
"H00964","Thiopurine S-methyltransferase deficiency (TPMT deficiency)","Thiopurine S-methyltransferase deficiency (TPMT deficiency) is inherited severe intolerance to thiopurine toxicity, caused by mutation in the TPMT gene. TPMT is part of a cascade of enzymes responsible for the metabolism of thiopurine drugs including azathioprine, mercaptopurine, and thioguanine.","Inherited metabolic disease"
"H00158","Lecithin:cholesterol acyltransferase deficiency","Lecithin:cholesterol acyltransferase (LCAT) deficiency is an autosomal recessive disorder of HDL metabolism characterized by low HDL-cholesterol level in blood and accumulation of free cholesterol in tissue leading to a triad of corneal dystrophy, hemolytic anemia, and proteinuria.","Inherited metabolic disease"
"H00990","Microcephaly, Amish type","Microcephaly, Amish type (MCPHA) is a lethal, autosomal resessive condition characterized by severe congenital microcephaly, elevated levels of alpha-ketoglutarate in the urine, and premature death. This disorder has been observed in Old Order Amish families. Patients have a homozygous point mutation in SLC25A19 that results in loss of transport activity.","Congenital malformation"
"H01842","Bickerstaff brainstem encephalitis","Bickerstaff's brainstem encephalitis (BBE) is a rare immune disorder in children, characterized by progressive ophthalmoplegia, ataxia, and disturbance of consciousness. Although the etiology of BBE is unknown, it has been linked to various antecedent infections. BBE is associated with the anti-GQ1b IgG antibody, which is present in 66% of a population of patients who had BBE. An autoimmune mechanism produced by microbial infection may trigger its pathogenesis. IVIG is effective in immune-mediated disorders such as Fisher syndrome (FS) and Guillain-Barre syndrome (GBS). IVIG is also effective in treatment of BBE, which is similar to the clinical and immunologic features of FS or GBS. Combined therapy of IVIG and high-dose methylprednisolone is a more efficacious therapy than IVIG alone. Most patients make a clinical recovery over six months.","Immune system disease; Nervous system disease"
"H01628","Opisthorchiasis","Opisthorchiasis comprises diverse clinical symptoms caused by infections with Opisthorchis felineus or Opisthorchis viverrini liver flukes, which are transmitted by eating infected raw or undercooked fish and other aquatic products.","Infectious disease"
"H02402","Thyroid eye disease","Thyroid eye disease (TED), also called Graves ophthalmopathy, is an autoimmune disorder of the retrobulbar tissue. It is the most frequent extrathyroidal manifestation of Graves disease [DS:H00082]. Although TED is often associated with hyperthyroidism, it may occur in primary hypothyroidism, and sometimes in euthyroid individuals.","Immune system disease"
"H00355","Leptospirosis","Leptospirosis is a zoonosis, caused by pathogenic spirochetes belonging to the genus Leptospira. Many mammalian species and amphibians may act as reservoirs. Leptospira colonize the renal tubules of chronically infected reservoir animals and are shed via urine into the environment, and then usually gain entry to the host via mucosal surfaces or damaged skin. Clinical symptoms range from a self-resolving acute febrile illness to severe, sometimes fatal disease (Weil disease).","Infectious disease"
"H01287","Congenital mirror movements","Mirror movements (MRMV) are involuntary movements of one side of the body that mirror intentional movements on the opposite side. While mirror movements are occasionally found in young children, persistence beyond the age of 10 is abnormal. Congenital mirror movements is a rare disorder that is mainly inherited in an autosomal-dominant fashion. Mutations in DCC, the gene encoding receptor for netrin 1 have been identified in MRMV patients. It has also been reported that RAD51 haploinsufficiency causes the heterogeneous MRMV.","Nervous system disease"
"H01889","Meier-Gorlin syndrome","Meier-Gorlin syndrome (MGS) is a genetically heterogeneous primordial dwarfism syndrome characterized by microtia, patellar aplasia/hypoplasia, and a proportionate short stature. Additional clinical findings include pulmonary emphysema, feeding difficulties, urogenital abnormalities, and mammary hypoplasia. Characteristic facial features, which gradually change with age, are frequently described. Infants typically have a small mouth with full lips and micrognathia, whereas in adults, a high forehead and a more prominent, narrow nose with a broad nasal bridge are distinguishable. The diagnosis of MGS should be considered in patients with at least two of the three features of the clinical triad of microtia, patellar anomalies, and pre- and postnatal growth retardation. Mutations in genes involved in DNA-replication have been detected in patients with MGS.","Congenital malformation"
"H00167","Phenylketonuria","Phenylketonuria (PKU) is one of the most common inborn errors of metabolism marked by a deficiency of the hepatic enzyme phenylalanine hydroxylase (PAH), leading to a toxic accumulation of phenylalanine in the blood and multiple tissues and potentially to intellectual disability, delayed speech, seizures, and behavior abnormalities. Deficiency of tetrahydrobiopterin (BH4), the cofactor of PAH, is caused by defects of the enzymes in pterin biosynthesis. Because BH4 is also a cofactor of tyrosine hydroxylase and tryptophan hydroxylase in neurotransmitter synthesis, BH4-deficient hyperphenylalaninemia is characterized by neurotransmitter deficiencies.","Inherited metabolic disease; Nervous system disease"
"H00503","Ellis-van Creveld syndrome","Ellis-van Creveld syndrome is an autosomal recessive disorder of bone growth. Indivisuals with this condition have short ribs, postaxial polydactyly, and dysplastic teeth and nails. Congenital cardiovascular malformations are seen in 60% of the cases. Loss-of-function mutations in EVC1 or EVC2 genes and resulting hedgehog signaling defects are causative of this disease.","Congenital malformation"
"H02254","Craniosynostosis and dental anomalies","Craniosynostosis and dental anomalies (CRSDA) is an autosomal recessive form of craniosynostosis associated with delayed tooth eruption, maxillary hypoplasia, supernumerary teeth, and digit abnormalities. It was reported that affected children harbored mutations in IL11RA encoding interleukin 11 receptor, alpha. It has been suggested that IL11 signaling is essential for the normal development of craniofacial bones and teeth and that its function is to restrict suture fusion and tooth number.","Congenital malformation"
"H02066","Achondrogenesis type II","Achondrogenesis Type II (ACG2) is a lethal skeletal disorder caused by dominant mutations in the type II collagen gene (COL2A1). ACG2 is the most severe of the phenotypic spectrum of COL2A1 mutations.","Congenital malformation"
"H00731","Atrial fibrillation","Atrial fibrillation (AF, ATFB) is the most common cardiac arrhythmia and is regarded generally as a sporadic, acquired disorder. Nevertheless, recent growing evidence points to an important heritable basis for AF. By linkage analysis, several loci have been mapped for monogenetic AF. Some of these loci encode for subunits of potassium channels.","Cardiovascular disease"
"H01425","Lysosomal storage disease","Lysosomal storage diseases (LSDs) are a group of inherited diseases that are characterised by the intracellular accumulation of incompletely degraded macromolecules. They result from a genetic defect in cellular transport or metabolism of molecules within the lysosome. Most of the patients with a LSD are born apparently healthy and the symptoms develop progressively. Treatment is directed toward symptomatic care of secondary complications for most of these diseases. For some individuals, hematopoietic stem cell transplantation or enzyme-replacement therapy can be effective.","Congenital disorder of metabolism"
"H02092","von Willebrand disease","Von Willebrand disease (VWD) is the most common autosomally inherited bleeding disorder characterized by abnormal quantity or quality of von Willebrand factor (VWF). Type 1 VWD exhibits a mild to moderate reduction in functionally normal VWF; type 2 VWD involves the expression of functionally abnormal VWF (further subdivided into types 2A, 2B, 2M, and 2N); and type 3 VWD presents the virtually complete absence of VWF. Clinical symptoms of VWD include predominantly mild mucosal bleeding. Joint bleeding can occur in the most severe forms.","Hematologic disease"
"H01617","Foodborne trematodiasis","Foodborne trematode infections, which are caused by four main genera: Clonorchis spp. that cause clonorchiasis, Opisthorchis spp. that cause opisthorchiasis, Fasciola spp. that cause fascioliasis and Paragonimus spp. that cause paragonimiasis. Foodborne trematode infections are accomplished through ingestion of metacercariae by eating raw or insufficiently cooked freshwater fish (C. sinensis, Opisthorchis spp., Echinostoma spp., heterophyids, Metagonimus spp.), freshwater crab or crayfish (Paragonimus spp.), aquatic plants (Fasciola spp., Fasciolopis buski), snails or tadpoles (Echinostoma spp.), or by drinking contaminated water (Fasciola spp.).","Infectious disease"
"H01273","Autosomal dominant keratitis","Autosomal dominant keratitis (ADK) is a very rare ocular disorder characterised by corneal opacification and vascularization and by foveal hypoplasia. ADK is associated with mutations in the PAX6 gene, that is essential for ocular morphogenesis.","Nervous system disease"
"H00193","Dihydropyrimidine dehydrogenase deficiency","Dihydropyrimidine dehydrogenase enzyme deficiency is a pharmacogenetic syndrome leading to severe side-effects in patients receiving therapies containing the anticancer drug 5-fluorouracil.","Inherited metabolic disease"
"H01041","Aerococcus urinae infection","Aerococcus urinae is a rare pathogen that belongs to a gram-positive coccus. Most infections are mild, but fatal infections such as endocarditis and septicemia/urosepsis have also been described.","Infectious disease"
"H00133","Mucopolysaccharidosis type IX","Mucopolysaccharidosis type IX (MPS9) is a very rare autosomal recessive lysosomal storage disorder caused by deficient activity of lysosomal hyaluronidase.","Inherited metabolic disease; Lysosomal storage disease"
"H00301","Klebsiella infection","Klebsiella is a gram-negative bacterium of Enterobacteriaceae, which has emerged as an important cause of hospital-acquired infections. Infections caused by extended-spectrum beta-lactamase (ESBL)-producing pathogens, particularly Klebsiella pneumoniae, are increasing. ESBL are plasmid-mediated enzymes and these plasmids also carry resistance genes to other antibiotics including aminoglycosides, chloramphenicol, sulfonamides, trimethoprim, and tetracycline. Thus, Gram-negative bacilli containing these plasmids are multidrug-resistant. Klebsiella pneumoniae can cause sepsis, conjunctivitis, urinary tract infections, and surgical site infections. Bloodstream infections with Klebsiella markedly increase the rates of treatment failure and death.","Infectious disease"
"H02456","Ectodermal dysplasia","Ectodermal dysplasias (ECTD) are a heterogeneous group of disorders characterized by a deficiency of ectodermally derived tissues, including hair, skin, teeth, and sweat glands. These conditions feature various combinations which demarcate the various subtypes.","Congenital malformation"
"H00765","Spondyloepiphyseal dysplasia, Kimberley type","Spondyloepiphyseal dysplasia Kimberley type is a mild form of spondyloepiphyseal dysplasia (SED) with early-onset arthropathy. The phenotype of the disease is short stature and stocky build due to flattened vertebral bodies. Aggrecan, the protein of the proteoglycan of cartilage, is linked to the disease.","Congenital malformation"
"H02032","Entomophthoramycosis","The class Zygomycetes is divided into two orders, Mucorales and Entomophthorales. These two orders produce dramatically different infections. Genera from the order Mucorales cause an angioinvasive infection called mucormycosis. Genera from the order Entomophthorales produce a chronic subcutaneous infection called entomophthoramycosis in immunocompetent patients.","Infectious disease"
"H02200","Leukoencephalopathy, progressive, with ovarian failure","Leukoencephalopathy, progressive, with ovarian failure has a clinical presentation previously described as ovarioleukodystrophy. Some of the patients have a variant of vanishing white matter disease with mutations in subunits of EIF2B. Recently, novel phenotype related to AARS2 mutations has been reported. AARS2 encodes mitochondrial alanyl-tRNA synthetase. Patients with AARS2 mutations had childhood- to adulthood-onset signs of neurologic deterioration consisting of ataxia, spasticity, and cognitive decline. Female patients had ovarian failure.","Nervous system disease; Congenital disorder of metabolism"
"H01485","Autosomal recessive mental retardation-42","Autosomal recessive mental retardation-42 (MRT42) is a neurodevelopmental disorder. Clinic features are variable and include neonatal hypotonia, severe intellectual disability, and major and absence epilepsy. Homozygous mutation in PGAP1 has been identified.","Inherited metabolic disease"
"H00557","Cutis laxa","Cutis laxa is a heterogeneous group of connective tissue disorders with variable organ involvement. The most obvious symptom of cutis laxa is loose and sagging skin due to reduced elastic fibers in the dermis. The phenotype of autosomal recessive cutis laxa II includes abnormal growth, developmental delay, and associated skeletal abnormalities. Autosomal recessive cutis laxa III, also known as De Barsy syndrome, is characterized by an aged appearance with distinctive facial features, sparse hair, ophthalmologic abnormalities, and intrauterine growth retardation.","Congenital malformation"
"H01643","Chilblains","Chilblains, or pernio, is a localized inflammatory lesion of the skin resulting from an abnormal response to cold. It is characterized by persistent purple or purple-red nodules on acral skin, most commonly the feet. Chilblains occurs most commonly among young women between the ages of 15 and 30 years but may occur among older individuals or children. Treatment of chilblains is focused on keeping the affected area warm, and occasionally using vasodilator agents.","Skin and connective tissue disease"
"H00791","Disseminated superficial actinic porokeratosis (DSAP)","Porokeratosis is a disorder of keratinization characterized by atrophic patches surrounded by a ridge of keratin called cornoid lamella. Disseminated superficial actinic porokeratosis (DSAP) is the most common form of porokeratosis. It is induced by exposure to ultraviolet light and usually appears during the third or fourth decade.","Congenital malformation"
"H01471","Lymphangioma","Lymphangiomas are congenital malformations of the lymphatic system, which is located mostly on the head and neck region. The lesions consist of dilated endothelium-lined spaces that vary in size from microscopic channels (cavernous lymphangioma) to large cysts (cystic hygroma). Although histologically benign, these lesions may expand into surrounding tissues and/or infiltrate vital structures similar to malignancies, sometimes causing life-threatening complications. The etiology of lymphangioma is not certain. The presence of lymphatic endothelial cell (LEC)-specific markers on the endothelial lining of lymphangiomas (e.g. the transcription factor Prox1) indicates that the neoplasm may result from transformed LECs and/or stromal cells. This transformation is modulated by VEGF-C, a specific lymphatic endothelial growth factor, and its receptor VEGFR-3.","Vascular disease"
"H01015","Jalili syndrome","Jalili syndrome is a combination of recessively inherited cone-rod dystrophy and amelogenesis imperfecta. It is caused mutations in the CNNM4 gene that encodes a putative metal transporter that expressed in the neural retina and in ameloblasts in the developing tooth.","Nervous system disease"
"H01829","Acute encephalitis with refractory repetitive partial seizures","Acute encephalitis with refractory, repetitive partial seizures (AERRPS) is a new epileptic syndrome mainly affecting children. AERRPS has not been perceived in Western countries, although it is widely recognized in Japan. They usually present abruptly with seizure or impaired consciousness as well as high-grade fever following antecedent infection. Seizures in AERRPS are almost exclusively of localized origin, whose semiology includes eye deviation, hemifacial twitching, hemiclonic convulsion, and autonomic manifestations. Partial seizures are brief, but repeat with increasing frequency and develop status epilepticus at nadir. It is followed by continuous transition to intractable epilepsy without a latent period. They are uniformly resistant to conventional antiepileptic drugs. In most cases, high-dose barbiturate treatment is necessary during the acute phase of the illness. Benzodiazepines, mainly midazolam, were partially effective in some patients. The pathogenesis of AERRPS is still poorly understood. It is currently suspected to represent an inflammatory disorder of the central nervous system.","Nervous system disease"
"H01227","Inflammatory bowel disease (IBD)","Inflammatory bowel disease (IBD) is a heterogeneous group of chronic disorders, which includes Crohn's disease and ulcerative colitis. Patients suffer chronically from abdominal pain, diarrhea, bleeding, and malabsorption. In most patients, these disorders are manifested in adolescence or adulthood, however, they may present in infancy and may be inherited as an autosomal recessive trait. It has been reported that mutations in genes encoding the IL10R subunit proteins were found in patients with early-onset enterocolitis, involving hyperinflammatory immune responses in the intestine. Additional genes associated with the disease have been identified.","Immune system disease"
"H00568","Myotonic dystrophy","Myotonic dystrophy (DM) is a complex multisystemic disorder linked to two different genetic loci. DM1 is caused by an expansion of a CTG repeat located in the 3' untranslated region (UTR) of DMPK. DM2 is caused by an unstable CCTG repeat in intron 1 of ZNF9. Therefore, both DMs are caused by a repeat expansion in a region transcribed into RNA but not translated into protein. The mutant RNA transcripts aberrantly affect the splicing of the same target RNAs, such as chloride channel 1 (ClC-1) and insulin receptor (INSR), resulting in their shared myotonia and insulin resistance. Affected individuals express highly heterogeneous, multisystemic symptoms including myotonia (muscle hyperexcitability), progressive muscle weakness and wasting, cataract development, testicular atrophy, and cardiac conduction defects. It has an autosomal dominant mode of inheritance and disease severity generally correlates with repeat length.","Nervous system disease; Musculoskeletal disease"
"H01688","Rapidly progressive glomerulonephritis","Rapidly progressive glomerulonephritis (RPGN) or crescentic glomerulonephritis is a life-threatening disease that destroys kidneys over a period of days to weeks. Proliferation of epithelial cells and infiltration of inflammatory cells lead to glomerular crescent formation and disruption of the specialized microvascular network in the glomerulus. This causes hematuria, albuminuria and loss of renal function. From an immunopathologic standpoint, primary RPGN is divided into pauci-immune GN (PIGN), anti-glomerular basement membrane antibody (anti-GBM) GN, and immune complex GN. PIGN, the most common etiology of primary RPGN, refers to a necrotizing glomerulonephritis with few or no immune deposits by immunofluorescence or electron microscopy. Approximately 90% of patients with PICG have circulating ANCA antibodies, leading to the systemic small vessel vasculitis such as granulomatosis with polyangiitis (GPA). Corticosteroids and cyclophosphamide are the first-line treatment, but infection is the most common cause of death of RPGN patients. Several new treatment strategies, such as leukocytaphereis (LCAP) and intravenous immunoglobulin (IVIg), have become available and these treatments have made it possible to treat high-risk RPGN patients without inducing serious immunosuppressive states.","Urinary system disease"
"H02469","Cone-rod synaptic disorder","Cone-rod synaptic disorder (CRSD) is an autosomal recessive disorder caused by mutations in CABP4. CRSD is characterized by congenital nystagmus, stable low vision, photophobia, and a normal fundus appearance. Recently, It has been reported that mutations in RIMS2 cause a syndromic congenital cone-rod synaptic disease (CRSDS) with neurodevelopmental and pancreatic involvement.","Nervous system disease"
"H00930","Hypoalphalipoproteinemia","Hypoalphalipoproteinemia is a common finding in patients with premature coronary artery disease. Familial hypoalphalipoproteinemia syndromes are phenotypically heterogeneous. One form is associated with abnormal cellular cholesterol efflux caused by heterozygous mutations at the ABCA1 gene. Other forms are primary hypoalphalipoproteinemia caused by mutations of APOA1 gene.","Inherited metabolic disease"
"H01218","P14 deficiency","The deficiency of the late endosomal-lysosomal MEK binding partner 1 (MP1)-interacting protein (also known as p14 and MAPBPIP) causes a primary immunodeficiency syndrome comprising congenital neutropenia, partial albinism, short stature and B-cell and cytotoxic T-cell deficiency. This protein is an adaptor molecule orchestrating the subcellular anatomy of MAP kinase signaling, and is crucial for the function of neutrophils, B cells, cytotoxic T cells and melanocytes.","Primary immunodeficiency"
"H01816","Frank-ter Haar syndrome","Frank Ter Haar syndrome (FTHS) is a rare skeletal dysplasia with classical features like megalocornea, finger flexion deformities, prominent coccyx and heart defects. The main characteristics are brachycephaly, wide fontanels, prominent forehead, hypertelorism, prominent eyes, macrocornea with or without glaucoma, small chin, bowing of the long bones, and flexion deformity of the fingers. The most common underlying genetic defect in FTHS appears to be a mutation in the SH3PXD2B gene. Patients appeared to share many of the craniofacial and skeletal features normally associated with Melnick-Needles syndrome. However the autosomal recessive pattern of inheritance and congenital cardiac defects distinguished the syndrome as a separate entity.","Congenital malformation"
"H01220","Congenital cataracts, facial dysmorphism, and neuropathy","Congenital cataracts, facial dysmorphism, and neuropathy (CCFDN) syndrome is a rare autosomal recessive, complex developmental disorder exclusively manifested in the Roma population. CCFDN is a genetically homogeneous condition in which all patients are homozygous for the same ancestral mutation in the CTDP1 gene. Affected patients display congenital cataracts, microcornea, peripheral neuropathy, mild facial dysmorphism, hypogonadism, and psychomotor delay.","Congenital malformation"
"H01012","Oculo-auricular syndrome","Oculo-auricular syndrome is a rare developmental recessive condition characterized by ophthalmic anomalies and a particular cleft ear lobule. Previously described ocular abnormalities include bilateral microcornea, posterior synechiae, cataract, chorioretinal colobomas, and rod-cone dystrophy. Mutation in the human Hmx1 ortholog HMX1 (NKX5-3) results in this disease.","Congenital malformation"
"H01476","Behcet disease","Behcet disease is a multisystemic inflammatory disease characterized by relapsing episodes of oral aphthous ulcers, genital ulcers, other skin lesions, and uveitis. It can also involve visceral organs such as the gastrointestinal tract, pulmonary, musculoskeletal, cardiovascular and neurological systems. This disease is more common in countries along the ancient Silk Road, including Asia, Middle East, and Mediterranean. Although the etiology is still unknown, this disease is believed to be triggered by environmental factors such as microbial agents in individuals with a particular genetic background. The positive association of HLA-B51 was identified more than four decades ago, and has been confirmed in multiple populations. Recent genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Behcet disease.","Immune system disease; Skin and connective tissue disease"
"H01644","Blepharitis","Blepharitis is a chronic inflammatory condition of the eyelids associated with itchiness, redness, flaking, and crusting. It is among the most common ocular conditions affecting both children and adults. The etiology is complex and not fully understood, but the general consensus is that bacteria and inflammation contribute to the pathology. Blepharitis can be classified into anterior blepharitis and posterior blepharitis. Anterior blepharitis describes inflammation of the eyelid skin and eyelash follicles and may be accompanied by squamous debris or collarettes. Anterior blepharitis has classically been associated with Staphylococcus infection and seborrheic dermatitis. Posterior blepharitis describes inflammation of the meibomian glands and their orifices and may be a result of or cause of meibomian gland dysfunction (MGD). MGD is one cause of posterior blepharitis but others include infectious or allergic conjunctivitis, and rosacea. The diagnosis of blepharitis is almost always based on the history and clinical examination. Long-term management of symptoms may include daily eyelid cleansing routines and the use of therapeutic agents that reduce infection and inflammation. Recent clinical trials have shown that antibiotics and topical corticosteroids can produce significant improvement in signs and symptoms of blepharitis.","Nervous system disease"
"H00796","Dermatopathia pigmentosa reticularis","Dermatopathia pigmentosa reticularis is a rare disorder of pigmentation characterized by a triad of reticulate hyperpigmentation, nonscarring alopecia, and onychodystrophy. Other symptoms observed in the disease are palmoplantar keratoderma and hypohidrosis.","Congenital malformation"
"H02207","Kufor-Rakeb syndrome","Kufor Rakeb syndrome (KRS), also known as Parkinson disease 9 (PARK9), is an autosomal recessive disorder characterized by subacute, juvenile onset, levodopa responsive parkinsonism, pyramidal signs, dementia, and a supranuclear gaze palsy. It has been reported that brain MRI revealed generalized atrophy and putaminal and caudate iron accumulation bilaterally. KRS is due to ATP13A2 gene mutations.","Nervous system disease"
"H01482","Infantile hemangioma","Infantile hemangiomas (IH) are neoplastic proliferations of vascular endothelial cells (ECs), characterized by a period of growth after birth, and eventual spontaneous involution. Forty percent of the lesions are associated with complications such as ulceration, bleeding, infection, pain, cardiac failure, airway compromise or eye impairment. Pathogenesis of IH is still shrouded in mystery even though various theories have been postulated to explain its origin. Recent studies provide strong evidence for the conclusion that the VEGF receptor 2 (VEGFR2) and Tumor Endothelial Marker 8 (TEM8) mutations represent risk factor mutations for hemangioma formation. In the proliferating phase, constitutive VEGFR2 signaling in ECs from hemangioma lesions affects downstream processes, including EC proliferation and migration, providing a mechanistic explanation for the rapid endothelial proliferation seen in hemangioma.","Vascular disease"
"H00550","Complete transposition of the great arteries","Complete transposition of the great arteries is a congenital heart defect with atrioventricular concordance and ventriculoarterial discordance in which the aorta arises from the morphologic right ventricle and the pulmonary artery arises from the morphologic left ventricle, resulting in severe cyanosis. Transposition of the great arteries (TGA) is frequently associated with other cardiac malformations such as ventricular septal defect. TGA is divided into three groups. Group I is TGA with intact ventricular septum. Group II is TGA with ventricular septal defect. Group III is TGA/VSD with pulmonary stenosis.","Developmental disorder; Cardiovascular disease"
"H00762","Spondyloepiphyseal dysplasia with congenital joint dislocations","Spondyloepiphyseal dysplasia with congenital joint dislocations (SEDCJD) is also known as SED Omani type. Knees, hip and elbow dislocations are common. Thoracic kyphoscoliosis develops in late childhood. Affected individuals are homozygous for a missense mutation of CHST3 encoding the enzyme chondroitin 6-O-sulfotransferase-1 (C6ST-1).","Congenital malformation"
"H02035","Isolated growth hormone deficiency","Isolated growth hormone deficiency (IGHD) is conditions associated with childhood growth failure due to lack of growth hormone (GH) action, and not necessarily associated with other pituitary hormone deficiencies or with an organic lesion. About 5-30% of patients are found to have affected first-degree relatives, suggesting genetic causes. IGHD has been classified into three types. IGHD type 1, characterized by autosomal recessive transmission, is further separated into subtypes 1A and 1B. The phenotype of IGHD type 1B is milder than that of IGHD type 1A. IGHD type 2 is inherited in an autosomal dominant pattern. IGHD type 3 is an X-linked recessive disorder with a highly variable phenotype. Some individuals have an associated agammaglobulinemia.","Endocrine disease"
"H00306","Pasteurellosis","Pasteurella species are gram-negative facultative anaerobic bacilli found in the animal's oral cavity. Most human infections are caused by dog or cat bites. Disseminated Pasteurella infections can lead to serious diseases including septic shock and meningitis mostly in infants and pregnant women.","Infectious disease"
"H02451","Congenital disorder of glycosylation with defective fucosylation","Congenital disorder of glycosylation with defective fucosylation (CDGF) a rare inherited metabolic disorder due to abnormalities in fucosylation, which is an enzymatic process of incorporating L-fucose into the N- and O-glycans of proteins or glycolipids. Fucosylation requires both the generation of the donor substrate GDP-fucose and the presence of a set of fucosyltransferases.","Congenital disorder of metabolism"
"H00134","X-linked ichthyosis","X-linked ichthyosis (XLI) is caused by deficient activity of steroid sulfatase. It is often associated with further clinical problems, including cryptorchidism or social communication deficits, such as attention deficit hyperactivity syndrome or autism.","Congenital disorder of metabolism; Congenital malformation"
"H00908","Mowat-Wilson syndrome","Mowat-Wilson syndrome (MWS) is a multiple congenital anomaly syndrome characterized by a distinct facial phenotype, intellectual deficiency, epilepsy and variable congenital malformations including Hirschsprung disease, genitourinary anomalies, congenital heart defects, agenesis of the corpus callosum and eye anomalies. MWS is caused by heterozygous mutations or deletions of the ZEB2/ZFHX1B gene.","Congenital malformation"
"H01449","Excoriation disorder","Excoriation Disorder, also known as Skin Picking Disorder, is characterized by the repetitive and compulsive scratching or picking of skin, which causes tissue damage. Patients spend a significant amount of time each day picking their skin, that causes psychosocial impairment. Triggers to pick vary greatly. For example, stress, anxiety, boredom, and feeling tired or angry have all been reported as triggers. Co-occurring psychiatric conditions are common in this disease. The most commonly reported comorbid conditions are trichotillomania, substance dependence, major depressive disorder, anxiety disorders, obsessive compulsive disorder (OCD), and body dysmorphic disorder (BDD). So far, there is no clear neurobiological explanation for the etiology of this disease. Recent research showed bilateral abnormalities in the anterior cingulate cortex and abnormalities on the left temporoparietal junction. Another study has shown deficits in motor inhibition, which appears to be correlated with frontal cortex abnormalities. Furthermore, severity of excoriation disorder may be associated with higher levels of impulsivity. Treatment for this disease has largely focused on cognitive behavioral therapy and pharmacology. Early psychosocial treatment studies provided evidence for skin picking reduction with habit reversal or acceptance-enhanced behavior therapy (AEBT). The data for selective serotonin reuptake inhibitors (SSRIs) efficacy in this disease are not convincing, although some studies suggested that fluoxetine is effective. Tricyclic antidepressants, neuroleptics, and the dopamine-blocking opioid antagonist have also been found to be effective for skin-picking.","Mental and behavioural disorder"
"H01811","Arima syndrome","Arima syndrome (AS) is a rare autosomal recessive disease characterized by severe psychomotor retardation, dysmorphic face, nystagmus, retinopathy, cystic kidney disease, and brain malformation. AS shares clinical and neuroradiological features with Joubert syndrome and related disorders, that is called ciliopathy. On brain magnetic resonance imaging (MRI), AS shows characteristic anomalies of the brainstem and cerebellum, such as the molar tooth sign (deformity of the brainstem isthmus and superior cerebellar peduncles) and cerebellar vermis hypoplasia.","Tenorio syndrome"
"H00937","Precocious puberty","Precocious puberty has been classically defined as the onset of secondary sexual characteristics in girls younger than 8 years old and in boys younger than 9 and a half years old. Central precocious puberty (CEPREPU) refers to a gonadotropin-dependent type which results from premature activation of the hypothalamic-pituitary-gonadal axis (HPG). CEPREPU is much more frequent in girls than in boys (up to 20:1 ratio). Recently, kisspeptin receptor (KISS1R) and its ligand, kisspeptin, were revealed as major gatekeepers of puberty onset. Mutations of the KISS1R gene were described in patients with impaired pubertal development. On the other hand, it has been reported that heterozygous mutations of the LHCGR gene cause gonadotropin-independent precocious puberty in males, but have no detectable effects on prepubertal or postpubertal females.","Endocrine disease"
"H00339","Botulism","Botulism is an acute neuroparalytic illness caused by a botulinum toxin produced by Clostridium botulinum, an anaerobic, gram-positive bacterium. Botulism occurs in four forms: foodborne, wound, infant botulism, and adult intestinal toxemia. Botulinum toxin blocks acetylcholine release in a dose-dependent fashion, resulting in symmetrical, descending, and progressive muscle weakness. Delay in treatment may allow progression of paralysis.","Infectious disease"
"H02238","Spinal muscular atrophy with congenital bone fractures","Spinal muscular atrophy with congenital bone fractures (SMABF) is a rare autosomal recessive disorder. Affected individuals presented with prenatal-onset spinal muscular atrophy, multiple congenital contractures, respiratory distress, and congenital bone fractures. It has been reported that mutations in two genes (TRIP4 and ASCC1) are associated with this disease. Both TRIP4 and ASCC1 encode subunits of the nuclear activating signal cointegrator 1 (ASC-1) complex.","Musculoskeletal disease"
"H00592","Calpainopathy","Limb-girdle muscular dystrophy 2A (LGMD2A) is caused by mutations in the CAPN3 gene encoding for calpain-3, a nonlysosomal calcium-dependent protease. This form of disorder is characterized by progressive muscle weakness and atrophy of the shoulder and pelvic girdle musculature, an elevated serum creatine kinase activity and a degeneration/regeneration pattern in muscular biopsy samples.","Nervous system disease; Musculoskeletal disease"
"H01440","Acute necrotizing ulcerative gingivitis","Acute necrotizing ulcerative gingivitis, also known as Trench mouth, Vincent angina and Vincent gingivitis is an acute bacterial infection of the gingiva caused by spirochetes, fusiform bacteria, or an overgrowth of normal oral flora. Predisposing factors include poor oral hygiene, advancing age, impaired nutritional status, smoking or chewing tobacco, immunosuppression, preexisting gingivitis, extreme stress, or lack of sleep. If the symptom progresses, the periodontium may be destroyed. Possible systemic manifestations include fever, anorexia, weakness, and fatigue.","Infectious disease"
"H01672","Juvenile idiopathic arthritis","Juvenile idiopathic arthritis (JIA) is one of the most common childhood rheumatic diseases. Clinically, it is defined as arthritis of unknown origin that starts before the age of 16, and persists for at least 6 weeks. Next to a certain genetic predisposition, environmental factors play a role leading to a chronic inflammatory response. JIA is not a single disorder but consists of a heterogeneous group of auto-immune inflammatory diseases. It has variable rates in course and activity of disease. Based on 6 months of clinical symptoms and global prognostic factors, the following clinical subtypes of JIA are recognized: systemic JIA, oligoarthritis, RF-negative polyarthritis, RF-positive polyarthritis, psoriatic JIA, enthesitis- related arthritis, and undifferentiated arthritis. Systemic JIA, also known as Still's disease, is a subtype with strong systemic clinical symptoms. Patients with systemic JIA have, in addition to arthritis, prominent symptoms of systemic inflammation such as spiking fever, rash, pericarditis, peritonitis, lymphadenopathy and organomegaly. A severe and often life-threatening complication occurring in 10-30% of patients with systemic JIA is macrophage activation syndrome. Polymorphisms in the IL6 and in the MIF gene have been found to be associated with susceptibility to the disorder. Based on the known relevance of IL6 in JIA pathophysiology, tocilizumab has been investigated and approved for use in the treatment of systemic and polyarticular JIA.","Immune system disease"
"H02493","Al Kaissi syndrome","Al Kaissi syndrome (ALKAS) is an autosomal recessive syndrome characterized by growth retardation, spine malformation, facial dysmorphism, and developmental delay. It has been reported that affected individuals harbor mutations in CDK10. CDK10 is a protein kinase that partners with cyclin M to phosphorylate substrates such as ETS2 and PKN2 in order to modulate cellular growth.","Congenital malformation"
"H01216","Left ventricular noncompaction","Left ventricular noncompaction (LVNC) is a rare and potentially progressive cardiomyopathy, characterized by the presence of prominent trabeculations of the left ventricle, associated with progressive systolic failure, stroke and arrhythmia. It has been linked to mutations in several genes, including LIM domain binding protein 3 (ZASP), alpha-dystrobrevin (DTNA), and genes encoding the sarcomeric proteins, beta-myosin heavy chain (MYH7), alpha-cardiac actin (ACTC), and cardiac troponin T (TNNT2).","Cardiovascular disease"
"H01024","Hereditary mixed polyposis syndrome","Hereditary mixed polyposis syndrome (HMPS) is a rare condition characterized by mixed hyperplastic, adenomatous and juvenile polyps and is associated with an increased risk of colorectal carcinoma. HMPS is linked to mutations in the BMPR1A gene.","Gastrointestinal disease"
"H01818","Dravet syndrome","The Dravet syndrome is a rare form of epileptic encephalopathy, and is accompanied by impaired psychomotor and neurologic development, occurring in the first year of life in apparently normal infants. Patients typically present with febrile hemiclonic or generalised tonic-clonic status epilepticus, followed by the development of other seizure types including myoclonic, focal, absence and atonic seizures between 1-4 years. All seizure types are pharmacoresistent, but a trend toward less severe epilepsy and cognitive impairment is usually observed after the age of 5 years. Development is normal in the first year of life with subsequent developmental slowing and sometimes regression. Approximately 80% of patients have point mutations or small insertions or deletions in the SCN1A gene.","Nervous system disease"
"H02467","Neonatal inflammatory skin and bowel disease","Neonatal inflammatory skin and bowel disease (NISBD) is a rare autosomal recessive disorder characterized by inflammatory features with neonatal onset, involving the skin, hair, and gut. A few gene mutations that cause NISBD have been identified.","Immune system disease"
"H00330","Methicillin-resistant Staphylococcal aureus (MRSA) infection","Methicillin-resistant Staphylococcus aureus (MRSA) is one of the major multidrug-resistant bacteria which have become endemic in the hospital environment, particularly in intensive care units (ICUs). Originally limited to the hospital setting, MRSA is a growing cause of infections in the community. Community-associated MRSA (CA-MRSA) strains are genetically different from MRSA strains originating in the hospital. Its increase in the community is of concern because CA-MRSA strains appear to be highly virulent, and colonization with CA-MRSA is often undetected in hospitalized patients, which can facilitate its potential for becoming resistant to multiple antibiotics. Health care-associated MRSA (HA-MRSA) is usually associated with pneumonia, urinary tract, blood stream, and surgical wound infections. In contrast, CA-MRSA strains are overwhelmingly associated with skin and soft tissue infections.","Infectious disease"
"H00102","Classic complement pathway component defects","Complement disorders account for only 2 percent of all primary immunodeficiency disorders. They result from the disruption of one of the proteins involved in the classic or nonclassic activation pathways of the complement response. Defects in the classic pathway account for the more common type of complement deficiency, and are associated with increased risk to develop systemic lupus erythematosus (SLE) and SLE-like diseases. Homozygous C2 deficiency, which is the most frequent hereditary deficiency in complement classical pathway components, is associated with SLE in 10% of the cases. Complete C1q and C4 deficiencies are less frequent but associated with a higher prevalence of SLE.","Primary immunodeficiency"
"H00566","Distal myopathy with anterior tibial onset","Distal myopathy with anterior tibial onset is an autosomal recessive muscle dystrophy caused by a dysferlin mutation. The disease is rapidly progressive, leading to severe proximal weakness.","Nervous system disease; Musculoskeletal disease"
"H02231","Optic disc anomalies with retinal and/or macular dystrophy","Optic disc anomalies with retinal and/or macular dystrophy (ODRMD) is an autosomal recessive ocular disorder. It has been reported that a homozygous SIX6 mutation is associated with optic disc anomalies and macular atrophy and reduces retinal ganglion cell differentiation.","Congenital malformation"
"H02003","Pyruvate dehydrogenase E3-binding protein deficiency","Defects in the pyruvate dehydrogenase (PDH) complex is a major cause of primary lactic acidosis and neurological dysfunction in infancy. E3 binding protein (E3BP, formerly Protein X) mediates association between the E2 core and the E3 enzyme. Primary defects of the E3BP appear to be a rare cause of pyruvate dehydrogenase deficiency.","Inherited metabolic disease"
"H00754","3-Methylglutaconic aciduria","3-Methylglutaconic aciduria (MGCA) is a group of metabolic disorders characterized by increased urinary excretion of 3-methylglutaconic acid and 3-methylglutaric acid. Nine distinct forms of MGCA have been recognized.","Inherited metabolic disease"
"H01686","Idiopathic portal hypertension","Idiopathic portal hypertension (IPH) is a disorder generally classified as a noncirrhotic portal hypertension of unknown etiology, and is clinically characterized by portal hypertension, splenomegaly, and pancytopenia. The principal pathologic changes of IPH are devastation of the intrahepatic terminal portal radicles with considerable portal fibrosis and secondary atrophy of the liver parenchyma that follows portal thrombosis. The incidence varies considerably with the country. In contrast to its high prevalence in India, IPH is comparatively a rare disorder in Western countries. Middle-aged women are more prone to IPH in Japan. IPH usually suggests a benign prognosis, but sometimes is complicated with severe hemorrhage due to ruptured esophageal varices, or massive splenomegaly. It is mainly managed by supportive treatment such as endoscopic, radiological and/or surgical management for esophageal varices and/or splenomegaly. The definite etiology of IPH is still uncertain, but there are several theories on the potential pathogenesis of IPH. These theories include immunological disorders, infections, and genetic variants.","Liver disease"
"H01827","Rolandic epilepsy, mental retardation, and speech dyspraxia","Rolandic epilepsy is the most  frequent childhood focal epilepsy. Mutations in GRIN2A has been detected in atypical rolandic epilepsy associated with verbal dyspraxia or with dysphasia. Recently, SRPX2 has been identified as being responsible for rolandic epilepsy associated with speech dyspraxia and mental retardation.","Nervous system disease"
"H01229","Inclusion body myopathy 3","Inclusion body myopathy 3 (IBM3) is an autosomal dominant myopathy associated with a heterozygous missense mutation in the myosin heavy chain (MyHC) IIa gene (MYH2), changing the highly conserved and negatively charged glutamate at position 706 to the positively charged lysine (E706K). This region is important for myosin functioning during muscle contraction, because it undergoes conformational changes during adenosine triphosphate (ATP) hydrolysis. Clinical characteristics include congenital joint contractures, a progressive course in adulthood, and external ophthalmoplegia.","Nervous system disease; Musculoskeletal disease"
"H00559","von Hippel-Lindau syndrome","von Hippel-Lindau syndrome is an autosomal dominant disorder associated with tumors in the central nervous system and other organs. The most frequent tumors are cerebellar and retinal haemangioblastomas, pancreatic neuroendocrine tumors, renal cell carcinoma, phaeochromocytoma in the adrenal gland, epididymal cystadenoma, and endolymphatic sac tumours. Germline inactivation of VHL tumor suppressor protein leads to the upregulation of HIF and promotes to carcinogenesis.","Congenital malformation"
"H00901","Cystinuria","Cystinuria is a inherited disorder of re-absorptive transport of cystine and the dibasic amino acids ornithine, arginine and lysine in the proximal tubule and small intestine. Diagnostically, urinary levels of dibasic amino acids lysine, arginine, and ornithine, and most prominently, of cystine are constantly elevated. Plasma levels of these amino acids in general are at the lower end of the normal range. Patients with cystinuria often present with nephro- or urolithiasis at almost at any age with a clear preference in childhood due to elevated urinary cystine. Early diagnosis is important, as it allows prevention or diminution of kidney stones. Mutations in either interacting subunit SLC3A1 (rBAT) or SLC7A9 (b0,+AT) cause cystinuria. Cystinuria due to mutations in SLC3A1 is an autosomal recessive trait, whereas mutations in SLC7A9 can be seen as an autosomal dominant trait.","Inherited metabolic disease; Urinary system disease; Kidney disease"
"H02458","Hydrocephalus due to congenital stenosis of aqueduct of sylvius","Hydrocephalus due to congenital stenosis of aqueduct of sylvius (HSAS) is a rare X-linked disease characterized by severe hydrocephaly. HSAS is the most common of the inherited form of hydrocephalus. It is caused by mutations in the L1 cell adhesion molecule (L1CAM) gene.","Congenital malformation"
"H02004","Fumarase deficiency","Fumarase deficiency (fumaric aciduria) is a rare autosomal recessive metabolic disorder caused by deficient activity of fumarate hydratase (FH, fumarase), one of the constituent enzymes of the Krebs tricarboxylic acid cycle. Patients usually present early in infancy with a severe encephalopathy, including hypotonia, developmental retardation, and seizures. Many of them have died during the first several years of life.","Inherited metabolic disease"
"H00753","Urofacial syndrome","The urofacial syndrome (UFS) is an autosomal recessive disorder characterized by the combination of urological problems and distorted facial expression. Failure of the urinary bladder to void in patients with UFS leads to recurrent urinary tract infection and subsequent renal failure.","Urinary system disease"
"H01681","Acute pancreatitis","Acute pancreatitis ranges from a mild, self- limiting disease to a life-threatening condition with multiple organ failure. Abdominal pain is the predominant symptom. Nausea and vomiting may accompany the pain. Patients frequently have a low-grade fever, tachycardia, and hypotension. The most common causes of acute pancreatitis are alcohol abuse and gallstones. The currently accepted pathogenic mechanism includes autodigestion and acute inflammation of the pancreas by the activation of proteases of the pancreas and acute inflammatory cells. Severe acute pancreatitis is defined by the presence of organ failure persisting beyond 48 hour. Organ failure that develops during the early phase is set in motion by the activation of cytokine cascades resulting in systemic inflammatory response syndrome (SIRS). Although effective therapies for acute pancreatitis are still limited, protease inhibitors have been considered to be a potential treatment to inhibit the pancreatic inflammation.","Pancreas disease"
"H00561","Brachydactyly-mental retardation syndrome","Brachydactyly mental retardation syndrome (BDMR), also known as Albright hereditary osteodystrophy-like syndrome, is a complex disorder characterized by brachydactyly and mental retardation including autism spectrum disorder. It has been confirmed that this disease is associated with some deletions of 2q37. Individuals with BDMR and Smith-Magenis syndrome (SMS) have very similar features. Mutation of the BDMR-causative gene HDAC4 results in reduced expression of RAI1, whose haploinsufficiency leads to SMS.","Chromosomal abnormality"
"H02236","Keppen-Lubinsky syndrome","Keppen-Lubinsky syndrome (KPLBS) is a rare condition characterized by severely reduced facial adipose tissue and thin facial skin combined with severe developmental delay and hypertonia. KPLBS is caused by mutations in KCNJ6, which encodes an inwardly rectifying potassium channel.","Congenital disorder of metabolism"
"H00105","Mannose-binding lectin pathway component defects","There is an increasing number of clinical studies indicating that deficiency of the lectin pathway has been associated with an increased risk, severity, and frequency of infections but also autoimmune disorders. MBL deficiency is one of the most common human immunodeficiencies and arises primarily from three single point mutations in exon 1 of the MBL-2 gene. These mutations result in a failure to assemble fully functional multimeric protein. Inherited MASP-2 deficiency has been described as the result of a mutation causing the exchange of aspartic acid with a glycine at position 105, a position in the first domain, CUB1, involved in calcium binding. This mutation abolishes the binding to MBL and ficolins, and deprives MASP-2 of functional activity.","Primary immunodeficiency"
"H00939","Darsun syndrome","G6PC3 deficiency is a syndromic variant of severe congenital neutropenia associated by complex organ malformation. Patients often have cardiac defects such as atrial septal defects, an increased superficial venous marking, and urogenital malformations. In the absence of G6PC3, increased ER stress makes neutrophils prone to undergo apoptosis and leads to defective organ development.","Congenital malformation"
"H02460","Neurodevelopmental disorder with dysmorphic facies and skeletal anomalies","Neurodevelopmental disorder (NED) with dysmorphic facies and skeletal anomalies is a group of syndromic neurodevelopmental disorders. Some of them have complications in addition to dysmorphic facies and skeletal anomalies. Several underlying genetic causes of these diseases have been identified.","Congenital malformation"
"H00337","Tetanus","Tetanus is a serious, often fatal intoxication caused by infection of Clostridium tetani, a gram-positive bacterium, through cuts or wounds. Mortality rate among untreated patients is high. Tetanus affects the muscles and nerves and manifests as muscle spasms in the jaw (lockjaw). Tetanus can be prevented by getting the tetanus vaccine.","Infectious disease"
"H01023","Juvenile polyposis syndrome","Juvenile polyposis syndrome (JPS) is an autosomal dominant condition identified by the presence of multiple benign, non-cancerous polyps called juvenile polyps in the gastrointestinal tract. A germline mutation in the SMAD4 or BMPR1A gene is found in about 50%-60% of patients with JPS. These genes play a role in the BMP/TGF-beta signalling pathway.","Gastrointestinal disease"
"H02494","Alkuraya-Kucinskas syndrome","Alkuraya-Kucinskas syndrome is an autosomal recessive syndrome characterized by brain atrophy with clubfoot and arthrogryposis. It has been reported that mutations in ALKKUCS are associated with this syndrome. ALKKUCS is required for synaptic vesicle recycling.","Congenital malformation"
"H01211","MECP2-related severe neonatal encephalopathy","MECP2-related severe neonatal encephalopathy is a rare disorder of males characterized by a static encephalopathy, severe developmental delays, hypotonia, seizures, and respiratory abnormalities that often leads to death at an early age. Mutations in the MECP2 gene cause this disease, and females with these same mutations typically have a disorder called Rett syndrome. Most boys with this disorder have been identified because they have female siblings with Rett syndrome.","Congenital malformation"
"H01675","Syringomyelia","Syringomyelia is a spinal disorder characterized by the presence of abnormal fluid-filled cavities within the spinal cord. Early symptoms include headache, altered pain and temperature sensation, and paresthesia. If fluid continues to enlarge the cyst, the syrinx has the potential to compress or destroy the affected portions of the spinal cord. Surgical intervention is typically recommended to treat this condition, although a successful procedure often is limited to providing minimal neurological improvement or simply halting the deterioration. The term syringomyelia describes many pathogenetically different disorders. A popular broad grouping is a classification based on the assumed pathogenesis and association with other disorders. It has been proposed to divide the disorder into three subgroups. (1) Syringomyelia as a result of changed cerebrospinal fluid (CSF) flow dynamics related to hindbrain disorders, e.g. Chiari malformation, Dandy-Walker syndrome, arachnoiditis or osseous abnormalities. (2) Syringomyelia as a result of intramedullary tissue damage caused by haemorrhage or infarction. (3) Syringomyelia as a result of intramedullary tumour with secretory capabilities. Other proposed classifications are based on syrinx fluid composition, central canal communication between syrinx and the fourth ventricle, or the microanatomical localisation of the syrinx.","Congenital malformation"
"H00595","Myofibrillar myopathies","Myofibrillar myopathy (MFM) is a group of genetically distinct disorders linked by common morphologic features observed on muscle histology. MFM is characterized by slowly progressive weakness that can involve both proximal and distal muscles. Distal muscle weakness is more pronounced than proximal weakness. All disease proteins identified to date are involved in maintaining the structural integrity of the Z-disk. The pathology includes accumulations of these proteins irrespective of primary gene defect, suggesting that these share molecular pathways involved in actin dynamics organized by the Z-disk. Besides accumulations of these proteins, congophilic amyloid products of myofibrillar degradation and ectopic aggregation of dystrophin and gelsolin appear in abnormal myofibers.","Nervous system disease; Musculoskeletal disease"
"H01447","Body dysmorphic disorder","Body dysmorphic disorder (BDD) is a psychiatric disorder in which individuals are preoccupied with imagined defects in their appearance, which are not noticeable or appear slight to others. It is characterized by time-consuming behaviors such as mirror gazing, comparing one's appearance with the appearance of others, excessive camouflaging to hide the defect, and seeking reassurance. Patients experience significant distress, disability, and functional impairment, often accompanied by depression and suicidality. There is some clinical and pathologic overlap between obsessive-compulsive disorder (OCD) and BDD such as obsessive thoughts and the performance of ritual behavior. Patients with BDD respond to treatment with serotonergic agents such as clomipramine or selective serotonin reuptake inhibitors (SSRIs), which suggests a dysfunction of central serotonergic neurotransmission as a possible etiological factor. A recent study suggests that cognitive-behavior therapy (CBT) was more effective than treatment with medications.","Mental and behavioural disorder"
"H00308","Vibrio vulnificus infection","Vibrio vulnificus is a gram-negative bacillus found in warm coastal waters. It causes two distinct syndromes: a primary septicemia related to seafood consumption and a necrotizing wound infection acquired by exposing open wounds to contaminated seawater.","Infectious disease"
"H00906","Macrocephaly, alopecia, cutis laxa, and scoliosis","Macrocephaly, alopecia, cutis laxa, and scoliosis is an autosomal-recessive disorder related to the cutis laxa group of inherited disorders associated with macrocephaly, sparse hair, redundant skin, hyperlaxity of joints, gingival hypertrophy, retrognathia with abnormal skull morphology, and severe scoliosis. Homozygous mutations in RIN2, a protein that is involved in the regulation of endocytosis, have been reported.","Skin and connective tissue disease"
"H02209","HARP syndrome","HARP (hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration) is a rare syndrome with many clinical similarities to pantothenate kinase associated neurodegeneration (PKAN). Both HARP and PKAN are caused by mutations in the gene encoding pantothenate kinase 2 (PANK2). HARP is distinguished by a specific lipoprotein abnormality. Patients have decreased or absent pre-beta lipoproteins consisting of very-low-density lipoproteins (VLDL).","Nervous system disease"
"H01478","Machado-Joseph disease","Machado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3), is one of the most common hereditary ataxias and is distributed worldwide. MJD is an autosomal dominant neurodegenerative disorder, involving predominantly the cerebellar, pyramidal, extrapyramidal, motor neuron and oculomotor systems. Minor, but more specific, features such as external progressive ophthalmoplegia (EPO), dystonia, intention fasciculation-like movements of facial and lingual muscles, as well as bulging eyes, may also be of major importance for the clinical diagnosis of MJD. The mean age at onset is around 40 years. MJD is associated with CAG repeat expansions in the ATXN3 gene. CAG repeat varies in size among affected persons. There is no effective treatment of ataxia. Case series and small controlled trials of several medications including antianxiolytics, antidepressants, and antiepileptics have shown limited efficacy.","Neurodegenerative disease"
"H00798","Familial carpal tunnel syndrome","Carpal tunnel syndrome is an entrapment neuropathy of the median nerve characterized by paresthesias in the district of the median nerve. Familial carpal tunnel syndrome is an extremely rare form with bilateral symptom that is frequently associated with inherited systemic disorders such as mucopolysaccharidosis, mucolipidosis, amyloidosis, collagen vascular disease or hereditary liability to pressure palsies. The cause of the disease is the compression of the median nerve by thickened transverse carpal ligament. Mutations in transthyretin, a gene that plays a role in deposition of amyloid, have been reported.","Nervous system disease"
"H01820","Carney complex","Carney complex (CNC) is a rare multiple neoplasia syndrome characterized by pigmented lesions of the skin and mucosa, cardiac, cutaneous and other myxomas, and multiple endocrine tumors. Further manifestations include primary pigmented nodular adrenocortical disease (PPNAD) [DS:H00260] leading to Cushing's syndrome [DS:H01431], pituitary adenomas [DS:H01102], thyroid nodules, testicular neoplasms, ovarian cysts, psammomatous melanotic schwannomas, ductal breast adenomas and osteochondromyxomas. Most CNC patients initially present with adrenocorticotropic hormone (ACTH)-independent Cushing's syndrome due to PPNAD or heart myxomas. Skin lesions are the most common CNC manifestation: lentigines are present in 70 to 75% of patients with CNC. Blue nevi are also typical of CNC. CNC is caused by inactivating mutations or large deletions of the PRKAR1A gene coding for the regulatory subunit type I alpha of protein kinase A (PKA). It may be inherited as an autosomal dominant trait but in a significant number of patients the disease is sporadic, presumably due to de novo mutations.","Other disease"
"H01952","Glycogen storage disease type XII","Glycogen storage disease type XII (GSD-XII) is an autosomal recessive disorder of glycogen metabolism. GSD-XII is caused by mutations in the ALDOA gene, which encodes the red cell aldolase. The typical presentation is hemolytic anemia, neurologic abnormalities, and myopathy with exercise intolerance.","Inherited metabolic disease"
"H00880","Dyschromatosis symmetrica hereditaria","Dyschromatosis symmetrica hereditaria (DSH) is a pigmentary genodermatosis of autosomal dominant inheritance. It presents in infancy or early childhood as a mixture of hyperpigmented and hypopigmented macules on dorsa of hands and feet. It is caused by a mutation of adenosine deaminase acting on the RNA 1 gene (ADAR1).","Skin disease"
"H01738","Noonan syndrome","Noonan syndrome (NS) is an autosomal dominant disorder characterised by short stature, craniofacial dysmorphism, congenital cardiac defects, cryptorchidism in men, coagulation defects, and neurocognitive delay. In addition, individuals with NS have an increased risk of developing cancer. NS is caused by germline mutations in genes that encode components or regulators of the Ras/MAPK pathway. Heterozygous, pathogenic variants in 9 known genes account for approximately 80% of cases. The most common gene associated with NS is PTPN11, which accounts for approximately 50% of all cases.","Congenital malformation"
"H02149","X-linked hypercalciuric nephrolithiasis","X-linked hypercalciuric nephrolithiasis (XLHN) includes four syndromes: X-linked recessive nephrolithiasis with renal failure, Dent disease, X-linked recessive hypophosphatemic rickets, and Low molecular weight proteinuria with hypercalciuria and nephrocalcinosis. These syndromes differ in degree from each other, but common themes include proximal tubular reabsorptive failure, nephrolithiasis, nephrocalcinosis, progressive renal insufficiency, and in some cases rickets. They were reported independently, but mutations in the chloride channel gene CLCN5 have been identified in all four syndromes.","Urinary system disease"
"H00874","Leukoencephalopathy with dystonia and motor neuropathy","Leukoencephalopathy with dystonia and motor neuropathy is a disorder caused by a deficiency of sterol carrier protein-2 (SCPx), a peroxisomal enzyme with thiolase activity, which is required for the breakdown of branched-chain fatty acids. The patient presents with torticollis and dystonic head tremor as well as slight cerebellar signs with intention tremor, nystagmus, hyposmia, and azoospermia.","Nervous system disease; Congenital disorder of metabolism"
"H00048","Hepatocellular carcinoma","Hepatocellular carcinoma (HCC) is a major type of primary liver cancer and one of the rare human neoplasms etiologically linked to viral factors. It has been shown that, after HBV/HCV infection and alcohol or aflatoxin B1 exposure, genetic and epigenetic changes occur. The recurrent mutated genes were found to be highly enriched in multiple key driver signaling processes, including telomere maintenance, TP53, cell cycle regulation, the Wnt/beta-catenin pathway (CTNNB1 and AXIN1), the phosphatidylinositol-3 kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway. Recent studies using whole-exome sequencing have revealed recurrent mutations in new driver genes involved in the chromatin remodelling (ARID1A and ARID2) and the oxidative stress (NFE2L2) pathways.","Cancer"
"H02182","Distal myopathy, Tateyama type","Distal myopathy, Tateyama type is a peculiar form of distal myopathy associated with reduced caveolin-3 in muscle fibers in which the muscle atrophy is restricted to the small muscles of the hands and feet. Gene analysis has been disclosed heterozygous mutations in the caveolin-3 gene.","Nervous system disease; Musculoskeletal disease"
"H01707","Ossified ligamentum flavum","Ossified ligamentum flavum (OLF) is a condition of heterotopic lamellar bone formation within the yellow ligament. OLF is a widely described pathology in eastern Asia and rare in other parts of the world. The disease process first causes hypertrophy of the ligamentum flavum and subsequent ossification, which narrows the spinal canal and leads to myeloradiculopathy. The lower thoracic spine is most commonly affected. Previous hyperkyphosis and mechanical stress are thought to be predisposing conditions. It is tempting to think that OLF is genetically or pathologically inherited based on abnormalities of calcium or phosphate metabolism, on endocrinologic abnormalities, or on the presence of autoimmune disease. Such relationships, however, have not been documented. Treatment of cervical stenosis related to OLF is based on the standard principle of managing neural spinal abnormalities. Acute episodes of pain and onset of or increase in neurological deficits are treated with rest, external spinal immobilization with a collar or brace, and analgesics, anti-inflammatory, and/or antispasmodic medicines. Surgery is indicated for patients with acute or chronic progression of neurological deficits or persistent neurological deficits.","Musculoskeletal disease"
"H01535","Eastern equine encephalitis","Eastern equine encephalitis is an infection of the central nervous system caused by Eastern equine encephalitis virus (EEEV), an alphavirus in the Togaviridae family of +ssRNA viruses, and transmitted by Culex mosquitoes. EEEV was first isolated in 1933 in Virginia, USA.","Infectious disease"
"H01151","Brevundimonas infection","Brevundimonas species are aerobic non-fermenting gram-negative bacilli. They are infrequently isolated from clinical samples and can cause opportunistic infections in patients with underlying diseases.","Infectious disease"
"H00083","Allograft rejection","Allograft rejection is the consequence of the recipient's alloimmune response to nonself antigens expressed by donor tissues. After transplantation of organ allografts, there are two pathways of antigen presentation. In the direct pathway, recipient T cells react to intact allogeneic MHC molecules expressed on the surface of donor cells. This pathway would activate host CD4 or CD8 T cells. In contrast, donor MHC molecules (and all other proteins) shed from the graft can be taken up by host APCs and presented to recipient T cells in the context of self-MHC molecules - the indirect pathway. Such presentation activates predominantly CD4 T cells. A direct cytotoxic T-cell attack on graft cells can be made only by T cells that recognize the graft MHC molecules directly. Nontheless, T cells with indirect allospecificity can contribute to graft rejection by activating macrophages, which cause tissue injury and fibrosis, and are also likely to be important in the development of an alloantibody response to graft.","Immune system disease"
"H01363","NARP syndrome","Neuropathy ataxia and retinis pigmentosa (NARP syndrome) is a mitochondrial disorder characterized by retinal, central and peripheral neurodegeneration. Point mutations of the mitochondrial DNA ATPase 6 gene cause this disease.","Inherited metabolic disease; Neurodegenerative disease; Mitochondrial disease"
"H01999","Pyruvate dehydrogenase E2 deficiency","Defects in the pyruvate dehydrogenase (PDH) complex is a major cause of primary lactic acidosis and neurological dysfunction in infancy. Recently, mutations in DLAT, the gene encoding dihydrolipoamide acetyltransferase, the E2 core component of the complex, have been described. Patients are less severely affected than typical patients with E1 mutations. Episodic dystonia was the major neurological manifestation.","Inherited metabolic disease"
"H00077","Progressive supranuclear palsy","Progressive supranuclear palsy (PSP) is a progressing degenerative disease belonging to the family of tauophaties caused by abnormalities in the microtubule-associated protein, tau. PSP presents with an atypical parkinsonism characterized by progressive axial rigidity, vertical gaze palsy, dysarthria and dysphagia. Although the majority of cases of progressive supranuclear palsy appear to be sporadic, the scarcity of familial cases may lack of recognition of the variable phenotypic expression of PSP. One in every 100,000 Americans over the age of 60 have PSP and patients are usually middle-aged or elderly, and men are affected more often than women.","Neurodegenerative disease"
"H01397","Tick-borne lymphadenopathy","Rickettsia species are arthropod-associated intracellular bacteria and cause diseases in human such as Tick-borne lymphadenopathy, Typhus fever and Spotted fever. Rickettsia slovaca has been isolated from Dermacentor ticks and is the main agent of tick-borne lymphadenopathy (TIBOLA), which is found only in Europe. Its symptoms are generally mild and can be characterized by inoculation eschar on the scalp and cervical lymphadenopathies after a tick bite. Moreover, most of the cases occur during European cool months related to the activity of Dermacentor ticks.","Infectious disease"
"H00245","Calcium sensing receptor (CASR) related disease","The mutations in the CASR gene which expresses in the parathyroid hormone producing chief cells of the parathyroid gland and the cells lining the kidney tubule affect calcium homeostasis. Loss-of-function mutations in the CASR gene are responsible for familial hypocalciuric hypercalcemia (FHH1) and for neonatal severe hyperparathyroidism (NSHPT). FHH1 is caused by homozygous mutations and characterized by benign symptoms with mild hypercalcaemia, whereas NSHPT is caused by homozygous mutations and characterized by more severe ones with severe hypercalcaemia and hyperparathyroid bone disease. Gain-of-function mutations are responsible for autosomal dominant hypocalcemia (ADH) that characterized by seizures in infancy, moderate hypocalcaemia and, absolute hypercalciuria.","Endocrine disease; Urinary system disease"
"H02176","Cryptorchidism","Cryptorchidism is the absence of at least one testicle from the scrotum. It is the most common birth defect involving the male genitalia. It is associated with a higher risk of developing testicular tumors in adulthood. Studies in humans have investigated the possibility that mutations in the INSL3 gene are the cause of cryptorchidism. It has shown that INSL3 is involved in testicular descent, however, mutations of this gene are not a frequent cause of cryptorchidism.","Congenital malformation"
"H00621","Alopecia neurologic defects and endocrinopathy syndrome","Alopecia neurological defects and endocrinopathy syndrome (ANE syndrome) is an autosomal recessive disease that is clinically heterogeneous. ANE syndrome patients display multiple signs including a varied amount of hair loss, mental retardation, progressive loss of motor ability beginning in the second decade of life, hypogonadism, central adrenal insufficiency, short stature, microcephaly, and several other skeletal and skin abnormalities. The syndrome is caused by decreased expression of the nucleolar protein RBM28, known to be required for biogenesis of the 60S subunit of the ribosome.","Ribosomopathy"
"H00413","Hepatitis C","Hepatitis C is a blood-borne infectious disease caused by Hepatitis C virus (HCV) belonging to the Flaviviridae family of +ssRNA viruses. HCV infection often becomes chronic and can lead to degenerative liver diseases including fibrosis and cirrhosis. Some of these may eventually lead to hepatocellular carcinoma.","Infectious disease"
"H02344","Cowchock syndrome","Cowchock syndrome (CMTX4) is a slowly progressive X-linked recessive disorder with axonal neuropathy, deafness, and cognitive impairment. This syndrome is associated with a mutation in AIFM1, the gene encoding apoptosis-inducing factor.","Nervous system disease"
"H00873","Cousin syndrome","Cousin syndrome arises from errors of morphogenesis. It is characterized by scapular and pelvic hypoplasia along with epiphyseal abnormalities, congenital dwarfism, and facial dysmorphy including cranial, cervical, and auricular malformations. Cousin syndrome is linked to TBX15 insufficiency.","Congenital malformation"
"H00619","Kenny-Caffey syndrome","Kenny-Caffey syndrome (KCS) is a rare hereditary bone dysplasia characterized by osteosclerosis with medullary stenosis of long bones with hypocalcemia and ocular abnormalities. Recurrent bacterial infections are common in patients with KCS. KCS is mostly inherited as an autosomal dominant trait. Recently, mutations in the FAM111A gene has been identified. Autosomal recessive cases have mutations in TBCE gene that encodes chaperone proteins of tubulins.","Congenital malformation"
"H02388","Infantile-onset limb and orofacial dyskinesia","Infantile-onset limb and orofacial dyskinesia (IOLOD) is a hyperkinetic movement disorder due to homozygous mutations in PDE10A, that encodes a dual cAMP-cGMP phosphodiesterase. PDE10A is enriched in the medium spiny neurons of the corpus striatum.","Nervous system disease"
"H01955","Glycogen storage disease type XV","Glycogen storage disease type XV(GSD-XV) is an autosomal recessive disorder of glycogen metabolism. GSD-XV is caused by mutations in the GYG1 gene, which encodes the glycogenin. The typical presentation is muscle weakness and cardiomyopathy.","Inherited metabolic disease"
"H00887","Lipoprotein glomerulopathy","Lipoprotein glomerulopathy is a rare hereditary disorder characterized by disturbed remnant lipoprotein catabolism and intravascular glomerular deposition of lipoprotein-containing thrombi. Patients usually present with proteinuria and hypertension, microhematuria is rare, and renal function becomes impaired. Rare mutations in apolipoprotein E (apoE) gene may contribute to the pathogenesis of the disease.","Inherited metabolic disease; Cardiovascular disease"
"H01169","Acetobacter infection","Acetobacter belongs to the group of acetic acid bacteria that oxidize alcohols or sugars incompletely. A. cibinongensis is one of the members that is mainly found in tropical fruits and flowers. A case of human infection with A. cibinongensis has been reported.","Infectious disease"
"H00289","Recurrent hydatidiform moles","Hydatidiform mole (HYDM) is an abnormal human pregnancy composed of hyperproliferative trophoblast occuring in approximately 1 in every 1500 pregnancies in Europe and North America. This incidence is higher in other areas in the world. Recurrent hydatidiform mole (RHM), the familial cases of the disease, is an autosomal recessive disorder in which molar tissues are diploid and have a biparental contribution to their genome. The molar tissues show abnormal epigenetic marking of maternal imprinted genes. Affected women have biallelic mutations in the NLRP7 gene (NALP7), a gene thought to be involved in inflammatory and apoptotic pathways.","Reproductive system diseases"
"H00414","Hepatitis D","Hepatitis D is caused by hepatitis D virus (HDV), also called hepatitis delta virus, which is a satellite that can infect human only in the presence of hepatitis B virus (HBV).","Infectious disease"
"H02343","EVEN-plus syndrome","EVEN-plus (epiphyseal, vertebral, ear, nose, plus associated findings) syndrome is a rare multiple congenital anomalies syndrome. Mutations in the HSPA9 gene, coding for the mitochondrial chaperone mortalin, cause EVEN-plus syndrome.","Congenital malformation"
"H02171","Rocio viral encephalitis","Rocio viral encephalitis is an infection of the central nervous system caused by Rocio virus (ROCV), a flavivirus in the Flaviviridae family of +ssRNA viruses, and transmitted by Culex mosquitoes. ROCV was first isolated in 1975 in Brazil.","Infectious disease"
"H00626","Focal segmental glomerulosclerosis","Focal segmental glomerulosclerosis (FSGS) is one of the most common forms of glomerular disorders leading to end stage kidney disease (ESKD). FSGS is defined as a clinicopathologic syndrome manifesting with high-grade proteinuria, associated with lesions of focal and segmental glomerular sclerosis and foot-process effacement. As the disease progresses, a more diffuse and global pattern of sclerosis evolves. FSGS accounts for 7-20 % of idiopathic nephrotic syndrome in children and 40 % in adults. There are two types of FSGS, primary (idiopathic) and secondary forms. The specific cause of primary FSGS has been ill-defined. Secondary FSGS is with recognized etiologic associations, including genetic mutations in podocyte-associated proteins, viruses, and drug toxicities. For the initial treatment of FSGS, corticosteroid and immunosuppressive therapy is recommended.","Urinary system disease"
"H01390","Mitochondrial neurogastrointestinal encephalomyopathy","Mitochondrial neurogastrointestinal encephalopathy (MNGIE) is an autosomal recessive neurodegenerative disorder associated with thymidine phosphorylase deficiency resulting in high levels of plasma thymidine and a characteristic clinical phenotype. The disease is characterized clinically by ptosis, progressive external ophthalmoparesis, gastrointestinal dysmotility, cachexia, peripheral neuropathy, and leukoencephalopathy. MNGIE is caused by TYMP mutations. Rare cases of MNGIE-like phenotype have been linked to RRM2B and POLG mutations.","Inherited metabolic disease; Neurodegenerative disease; Mitochondrial disease"
"H00242","Liddle syndrome","Liddle syndrome (LIDLS) is a rare form of autosomal dominant hypertension characterized by hypokalemic metabolic alkalosis, low-renin activity, and suppressed aldosterone secretion. The mutations in the epithelial Na+ channel gene cause failure of the protein endocytosis and accumulation of active channels at the cell surface, leading persistent absorption of Na+ and resulting in large blood volume and high blood pressure.","Cardiovascular disease"
"H00070","Galactosemia","Galactosemia (GALAC) is an autosomal recessive disorder caused by a defect in one of the enzyme genes for galactose metabolism. Newborns with the enzyme deficiency cannot properly metabolize milk sugar. Without treatment, toxic metabolites can cause severe growth problems including cataracts.","Inherited metabolic disease"
"H01364","3-Hydroxyacyl-CoA dehydrogenase deficiency","3-Hydroxyacyl-CoA dehydrogenase (HADH, SCHAD) deficiency is an autosomal recessive metabolic disorder, resulting from mutations in the HADH gene. HADH deficiency is one of the mitochondrial fatty acid oxidation disorder that has been the most recently described only in a few patients. The clinical phenotype of most patients that have been described is recurrent hypoglycemia associated with hyperinsulinism.","Inherited metabolic disease; Mitochondrial disease"
"H01156","STAR syndrome","STAR syndrome is an X-linked dominant disorder caused by mutations in the cyclin family member FAM58A characterized by syndactyly, telecanthus, and anogenital and renal malformations. The cardinal features of this syndrome are a characteristic facial appearance with apparent telecanthus and broad tripartite nasal tip, variable syndactyly of toes 2-5, hypoplastic labia, anal atresia, and urogenital malformations.","Congenital malformation"
"H00084","Graft-versus-host disease","Graft-versus-host disease (GVHD) is a lethal complication of allogeneic hematopoietic stem cell transplantation (HSCT) where immunocompetent donor T cells attack the genetically disparate host cells. GVHD pathophysiology can be summerized in a three-step process. Step 1 involves the development of an inflammatory milieu resulting from damage in the host tissues induced by the preparative chemotherapy or radiotherapy regimen. Damaged tissues secrete inflammatory cytokines, including interleukin 1 (IL-1), and tumor necrosis factor (TNF-alpha ). During step 2, antigen-presenting cells (APCs) trigger the activation of donor-derived T cells, which induce further T-cell expansion, induce cytotoxic T lymphocytes (CTL) and natural killer (NK) cells responses and prime additional mononuclear phagocytes to produce TNF-alpha and IL-1. Also, nitric oxide (NO) is produced by activated macrophages, and it may contribute to the tissue damage seen during step 3. During step 3, the effector phase, activated CTL and NK cells mediate cytotoxicity against target host cells through Fas-Fas ligand interactions and perforin-granzyme B.","Immune system disease"
"H01532","Gout","Gout is a kind of arthritis associated with hyperuricemia. It is triggered due to precipitation and deposition of inflammatory monosodium urate crystals in synovial and other tissues, accompanied by severe pain. The most common symptom include swelling, tenderness, warmth and redness. Mostly, the joint at the base of the big toe is affected, gout progresses with more frequent attacks that involve multiple joints. Joint pain that used to resolve in a week to 10 days could become a milder, but constant pain. Eventually, untreated gout can cause other comorbidities such as high blood pressure, diabetes, chronic kidney disease and cardiovascular disease. The incidence of the disease is more common in 40s men than women, but gout in women after menopause appears increased risk. Recently, the onset in 20s increases. The development of gout is not only associated with sex, age, race and genetics, but also diet and lifestyle are contributed to increasing prevalence of the disease. Epidemiology studies reported that the excessive intake of alcohol and purine rich food, which excessively produce uric acid, leads to accumulation of uric acid.","Musculoskeletal disease"
"H02185","Spondylometaphyseal dysplasia","The spondylometaphyseal dysplasias (SMD) are a group of short-stature disorders distinguished by abnormalities in the vertebrae and the metaphyses of the tubular bones. Aside from the most common SMD Kozlowski type (SMDK) and the second most common SMD corner fracture type (SMDCF), there are several rare subtypes and numerous unclassifiable cases of SMD.","Congenital malformation"
"H01700","Hypopituitarism","Hypopituitarism is a chronic endocrine illness, and is the partial or complete insufficiency of anterior pituitary hormone secretion. Anterior pituitary is composed of five cell types that secrete growth hormone (GH), prolactin (PRL), follicle-stimulating hormone (FSH) and luteinizing hormone (LH), thyroid stimulating hormone (TSH) and corticotropin hormone (ACTH). Clinical manifestations of hypopituitarism are variable, often insidious in onset and dependent on the degree and severity of hormone deficiency. However, it is associated with increased mortality and morbidity. A variety of diseases may cause hypopituitarism and, accordingly, this disorder can be divided into two types depending on its cause. Primary hypopituitarism is caused by disorders of the pituitary gland itself and may be due to the loss, damage, or dysfunction of pituitary hormone-secreting cells. On the other hand, secondary hypopituitarism is the result of diseases of the hypothalamus or pituitary stalk interrupting the nerve or vascular connections to the pituitary gland, thereby reducing the secretion of the pituitary hormones. Hypopituitarism can be easily diagnosed by measuring basal pituitary and target hormone levels. MR imaging of the hypothalamo-pituitary region may provide essential information. The most common causes of primary hypopituitarism are pituitary adenoma and complications from surgery or radiation therapy for the treatment of pituitary adenoma. In rare cases, hypopituitarism has been observed when the infection occurs. Sheehan's syndrome is hypopituitarism caused by the postpartum hemorrhage of the pituitary gland. In still rarer cases, solitary or complicated pituitary hormone deficiency syndromes may occur due to genetic causes and typically affect children. The treatment of hypopituitarism typically involves a replacement of the deficient hormone but care must be taken because several studies have reported an increased incidence of cardiovascular disorders and number of deaths among these patients.","Endocrine disease"
"H02178","MASA syndrome","MASA syndrome (mental retardation, aphasia, shuffling gait, and adducted thumbs) is an X-linked disorder. The main clinical features are summarised by the acronym. Mutations in the gene for neural cell adhesion molecule L1 (L1CAM) have been reported from families of MASA syndrome, X-linked recessive spastic paraplegia, and X-linked aqueductal stenosis or hydrocephalus (HSAS) and these syndromes form part of a clinical spectrum resulting from a heterogenous group of mutations in L1CAM.","Congenital malformation; Nervous system disease"
"H00845","Familial amyloidosis","The amyloidoses are a group of diseases in which proteins that are normally soluble deposit extracellularly in tissues as insoluble fibrils. The fibrils have a characteristic beta-pleated sheet configuration that renders them avid for Congo red dye. In the familial amyloidoses, a gene mutation inherited in an autosomal-dominant manner results in a single amino acid substitution that renders a plasma protein amyloidogenic. Mutations in the TTR gene are the most common cause of familial amyloidosis. The clinical features of familial amyloidosis vary depending on the underlying amyloidogenic protein and the particular amino acid affected by the mutation, ranging from peripheral and autonomic neuropathy to cardiomyopathy.","Nervous system disease"
"H01997","Pyruvate dehydrogenase E1-alpha deficiency","Defects in the pyruvate dehydrogenase (PDH) complex are an important cause of primary lactic acidosis. It can also present as a more chronic neurodegenerative disease with extensive cerebral atrophy and structural anomalies in the brain, as Leigh syndrome. The great majority of PDH complex deficiencies result from mutations in the X-linked pyruvate dehydrogenase (E1) alpha subunit gene.","Inherited metabolic disease"
"H00079","Asthma","Asthma is a complex syndrome with many clinical phenotypes in both adults and children. Its major characteristics include a variable degree of airflow obstruction, bronchial hyperresponsiveness, and airway inflammation. Inhaled allergens encounter antigen presenting cells (APC) that line the airway. Upon recognition of the antigen and activation by APC, naive T cells differentiate into TH2 cells. Activated TH2 stimulate the formation of IgE by B cells. IgE molecules bind to IgE receptors located on mast cells. The crosslinking of mast-cell-bound IgE by allergens leads to the release of biologically active mediators (histamine, leukotrienes) by means of degranulation and, so, to the immediate symptoms of allergy. Mast cells also release chemotactic factors that contribute to the recruitment of inflammatory cells, particularly eosinophils, whose proliferation and differentiation from bone marrow progenitors is promoted by IL-5. The activation of eosinophils leads to release of toxic granules and oxygen free radicals that lead to tissue damage and promote the development of chronic inflammation.","Immune system disease"
"H01399","Bacillus thuringiensis infection","Bacillus thuringiensis is a close taxonomic relative of Bacillus cereus and an insect pathogen that is widely used as a biopesticide. Additionally, this bacterium is known to induce myonecrosis in immunosuppressed mice after cutaneous infection. Human infection is unusual, and apart from gastrointestinal tract infections or those following laboratory contamination, there are only two clinical reports of B. thuringiensis infection. Both the cases were isolated from severe human tissue necrosis by burn wounds or severe war wounds.","Infectious disease"
"H01963","Duchenne muscular dystrophy","Duchenne muscular dystrophy (DMD) is a progressive, lethal X-linked neuromuscular disorder principally affecting males. It is caused by mutations in the DMD gene, which codes for dystrophin. Patients suffer from progressive muscle weakness, are wheelchair-bound before the age of 12 and often die before the third decade of their life.","Nervous system disease; Musculoskeletal disease"
"H01709","Glucocorticoid-induced osteonecrosis","Glucocorticoid-induced osteonecrosis is a common and severe adverse event. Glucocorticoid use is one of the most important causes of osteonecrosis. In patients receiving long-term therapy, glucocorticoids induce fractures in 30 to 50% and osteonecrosis in 9 to 40%. The pathogenesis of glucocorticoid-induced osteonecrosis is not fully understood but postulated mechanisms include hyperlipidemia, fat emboli and intravascular coagulation that reduce the supply of blood to the bones. Since not all patients who are treated with steroids develop osteonecrosis, the presence of additional risk factors or individual variation of glucocorticoids sensitivity has been suggested. The risks of this disease include advancing age, prolonged duration of treatment, increased daily dosage and cumulative dose, low body mass index, underlying disease, and polymorphisms in the glucocorticoid receptor. Bisphosphonates are first-line options for glucocorticoid-induced osteoporosis and may also be useful in glucocorticoid-induced osteonecrosis. It has been indicated that bisphosphonates may rapidly reduce pain, and delay joint collapse in patients with osteonecrosis.","Musculoskeletal disease"
"H00274","Papillon-Lefevre syndrome","Papillon-Lefevre syndrome (PLS) is an autosomal recessive disorder caused by deficiency of cathepsin C, a lysosomal cysteine proteinase that functions by removing dipeptides from the amino termini of its substrates. The disease is characterized by palmoplantar keratoderma and juvenile periodontitis.","Congenital disorder of metabolism; Congenital malformation"
"H00046","Cholangiocarcinoma","Cholangiocarcinoma is a highly malignant neoplasm that carries a poor prognosis and lacks effective therapy. It is the second most common primary hepatic tumor, and it is increasing in incidence and carries a high mortality. The tumor arises from the ductular epithelium of the biliary tree, either within the liver (intrahepatic cholangiocarcinoma: ICC) or more commonly from the extrahepatic bile ducts (extrahepatic cholangiocarcinoma). Several studies have demonstrated mutations resulting in overexpression of K-ras and p53 genes. These genetic alterations are associated with a more aggressive phenotype in this cancer. Many reports have implicated overexpression of the tyrosine kinase proto-oncogenes c-erbB-2 (HER-2/neu) and c-Met, as well as cyclo-oxygenase-2 (COX-2) activity in intrahepatic cholangiocarcinoma.","Cancer"
"H01194","X-linked chondrodysplasia punctata","Chondrodysplasia punctata (CDP) is a congenital disorder characterized by a skeletal abnormality, characterized by punctate calcification of the cartilage of the epiphyses, larynx and trachea. Different forms of CDP exist, the most common of which is inherited as an autosomal recessive trait (Rhizomelic CDP). CDP may also be inherited in a recessive and dominant X-linked fashion. The X-linked recessive CDP (CDPX1) characterized by facial anomalies with severe nasal hypoplasia, short stature, and distal phalangeal hypoplasia. Mutations in ARSE which encodes arylsulfatase E, showing a high sequence homology to steroid sulfatase. In X-linked dominant CDP (CDPX2), aberrant punctate calcification in cartilage is most prominent around the vertebral column, pelvis, and long bones. Additionally, CDPX2 patients may have asymmetric rhizomesomelia, sectorial cataracts, patchy alopecia, ichthyosis, and atrophoderma. It has been found that defects in D8-D7 sterol isomerase (EBP) cause CDPX2 and suggest a role for sterols in bone development.","Congenital malformation"
"H02375","Cardiac valvular defect, developmental","Cardiac valvular defect, developmental (CVDD) is non-syndromic severe congenital valve malformation. The identification of loss-of-function mutations in the PLD1 gene in two unrelated families with CVDD has been reported.","Congenital malformation"
"H00422","Glycoproteinoses","Glycoproteinoses is a group of autosomal recessive lysosomal storage diseases caused by deficient activty of enzymes that play important roles in the degradation of glycoproteins such as N-linked or O-linked oligosaccharides. The lack of a single enzyme leads to the complete blockage of the catabolic chain and results in the accumulation of undegraded oligosaccharides in lysosomes. Glycoproteinoses share many clinical features such as mental retardation, coarse facies, and dysostosis multiplex. Cathepsin A-deficiency causes combined sialidase and beta-galactosidase deficiency (Sialidosis and Galactosialidosis) due to its function in stabilising these two hydrolases.","Inherited metabolic disease; Lysosomal storage disease; Nervous system disease"
"H00610","Treacher Collins syndrome","Treacher Collins syndrome (TCS) is a rare congenital birth disorder characterized by severe craniofacial defects. Autosomal dominant TCS1 and TCS2 are caused by mutations in the TCOF1 and POLR1D genes, respectively. Autosomal recessive TCS3 is caused by mutations in the POLR1C gene. The majority of TCS cases are caused by a mutation in TCOF1 gene which encodes a putative nucleolar phosphoprotein known as treacle. It has suggested that treacle is involved in the production of ribosomal RNA within cells. POLR1C and POLR1D encode subunits present in RNA polymerase I and III. Both of these polymerases are involved in ribosomal RNA transcription.","Ribosomopathy"
"H02147","X-linked recessive nephrolithiasis with renal failure","X-linked recessive nephrolithiasis with renal failure (XRN) is a form of X-linked hypercalciuric nephrolithiasis. It is characterized by recurrent nephrolithiasis, nephrocalcinosis, and progressive renal failure, associated with mutations in a renal chloride channel gene, CLCN5.","Urinary system disease"
"H02381","Cleft palate, psychomotor retardation, and distinctive facial features","Cleft palate, psychomotor retardation, and distinctive facial features (CPRF) is a new genetic disorder that phenotypically resembles the Kabuki syndrome [DS:H00570] but with distinctive facial features, skeletal anomalies and, cognitive impairment. It has been reported that de novo mutations in KDM1A cause this disease. KDM1A is a histone demethylase that has been shown to play diverse and key roles in regulating gene expression during development.","Congenital malformation"
"H01504","Vogt-Koyanagi-Harada syndrome","Vogt-Koyanagi-Harada syndrome (VKHS), initially described as an uveomeningoencephalitic syndrome, is a rare systemic autoimmune disease that targets melanocyte-rich tissues, such as the eye, inner ear, meninges, skin and hair. This disease is characterized by panuveitis, often associated with neurologic and cutaneous manifestations, including headache, hearing loss, vitiligo, and poliosis. VKHS is more common in individuals of pigmented skin, such as Asians, Middle Easterners, Hispanics and Native Americans. Although the exact etiology of VKHS remains unclear, it has also been postulated that such an autoimmune response might be triggered by an infectious agent in a genetically susceptible individual. Several studies have demonstrated that HLA-DR4 is strongly associated with VKHD.","Immune system disease; Nervous system disease"
"H01736","Persistent truncus arteriosus","Persistent truncus arteriosus (PTA) is a rare congenital condition in which a solitary arterial trunk arises from the base of the heart and supplies the coronary, pulmonary and systemic arteries. It is recognized as the most severe phenotype of outflow tract defect, and survival into adulthood is dismal without surgery. It is often associated with an unfavorable prognosis because complete surgical repair is not always possible. Mutations in the NKX2-6 gene and GATA6 gene have been found in patients with PTA. The association between truncus arteriosus and chromosome 22q11 deletion is well recognized.","Cardiovascular disease"
"H00280","Enterotoxigenic Escherichia coli (ETEC) infection","Enterotoxigenic Escherichia coli (ETEC) infection is one of the main causes of infantile diarrhea in developing countries and an important etiologic agent for traveler's diarrhea. ETEC strains colonize the small intestine, secrete heat-labile (cholera toxin-like) and heat-stable enterotoxins, and cause watery diarrhea.","Infectious disease"
"H01352","Mitochondrial trifunctional protein deficiency","Mitochondrial trifunctional protein (TFP) deficiency is a rare autosomal recessive disorder that is caused by mutations in HADHA and HADHB. TFP is a multienzyme complex of the fatty acid beta-oxidation cycle. Human TFP is an octamer composed of four alpha-subunits harboring long-chain enoyl-CoA hydratase and long-chain L-3-hydroxyacyl-CoA dehydrogenase (LCHAD) and four beta-subunits encoding long-chain 3-ketoacyl-CoA thiolase (LCKAT). This disease includes a lethal neonatal phenotype with cardiomyopathy and Reye-like syndrome, an infantile hepatic phenotype with recurrent hypoketotic hypoglycemia, and a childhood or adolescent-onset neuromyopathic phenotype with peripheral neuropathy and recurrent rhabdomyolysis.","Inherited metabolic disease; Mitochondrial disease"
"H01160","Schizencephaly","Schizencephaly is a clinically and etiologically heterogeneous cerebral malformation presenting as unilateral or bilateral hemispheric cleft with direct connection between the inner and outer liquor spaces. Gray matter-lined clefts in the cerebral cortex and a range of neurological presentations are characteristic. Mutations in SIX3, SHH, and EMX2 have been reported.","Congenital malformation"
"H01964","Becker muscular dystrophy","Becker muscular dystrophy (BMD) is a X-linked neuromuscular disorder principally affecting males. It is caused by mutations in the DMD gene, which codes for dystrophin. In Becker muscular dystrophy, the distribution of muscle wasting and weakness is closely similar to that in Duchenne muscular dystrophy [DS:H01963], but the course of the disease is more benign.","Nervous system disease; Musculoskeletal disease"
"H01158","Alopecia universalis","Alopecia universalis is the most severe form of alopecia areata, characterized by generalized scalp and body atrichia with papular lesions. Mutations in the gene HR coding for the Hairless protein are associated with alopecia universalis. It is inherited in autosomal recessive manner.","Skin disease"
"H00842","Epidermodysplasia verruciformis","Epidermodysplasia verruciformis (EV) is a rare autosomal recessive genodermatosis, which is characterized by persistent human papillomavirus infection. The clinical features are lifelong eruption of pityriasis versicolor-like macules, flat wart-like papules and development of cutaneous carcinomas.","Skin disease"
"H01990","Muenke syndrome","Muenke syndrome is an autosomal dominant disorder characterized by coronal suture craniosynostosis, hearing loss, developmental delay, carpal and tarsal fusions, and the presence of the mutation P250R in FGFR3 gene.","Congenital malformation"
"H00628","Congenital bile acid synthesis defect","Congenital bile acid synthesis defects (CBAS) involve congenital deficiencies in enzymes responsible for catalyzing key reactions in bile acid synthesis. CBAS type 1, 2 ,3 and 4 are due to mutations in HSD3B7, AKR1D1, CYP7B1, and AMACR, respectively. Inherited mutations that impair bile acid synthesis cause a spectrum of human disease ranging from liver failure in early childhood to progressive neuropathy in adults.","Congenital disorder of metabolism"
"H00889","Lujan-Fryns syndrome","Lujan-Fryns syndrome (LFS) is a X-linked mental retardation (XLMR) syndrome, caused by mutations in the MED12 gene. LFS is characterised by tall stature with asthenic habitus, macrocephaly, a tall narrow face, maxillary hypoplasia, a high narrow palate, a small or receding chin, long hands with hyperextensible digits, hypernasal speech, hypotonia, mild-to-moderate mental retardation, behavioural aberrations and dysgenesis of the corpus callosum.","Congenital malformation"
"H01167","Granulibacter infection","Granulibacter is a gram-negative acetic acid bacterium that is recently reported to be a human opportunistic pathogen. Granulibacter has been isolated from patients with chronic granulomatous disease, in which phagocytes are not able to produce bactericidal superoxide anions. Bacteremia has also been observed in a non-immunocompromised patient with a history of intravenous drug abuse.","Infectious disease"
"H00287","Pyogenic sterile arthritis, pyoderma gangrenosum, and acne syndrome","Pyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome is a rare autoimflammatory disease with early onset, developing erosive arthritis. It is inherited in an autosomal dominant fashion. Patients typically develop cystic acne, abscesses and cutaneous ulcers, including pyoderma gangrenosum-like lesions. PAPA syndrome is caused by gain-of function mutations in PSTPIP1, a protein capable of associating with pyrin. Mutated PSTPIP1 reduces the inhibitory role of pyrin on inflammasome activation and therefore, potenciates the IL-1beta pathway. Elevated TNFalpha levels are also described.","Immune system disease"
"H01355","Kearns-Sayre syndrome","Kearns-Sayre Syndrome is a multisystem disorder characterized by ophthalmoplegia, pigmentary retinopathy, heart block, and cerebellar ataxia. This disease is caused by various large-scale deletions of mitochondrial DNA.","Nervous system disease; Congenital disorder of metabolism"
"H01731","Fragile X tremor/ataxia syndrome","Fragile X tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder affecting carriers of premutation CGG repeat expansions (range: 55-200) in the fragile X mental retardation 1 (FMR1) gene. Common manifestations of FXTAS are progressive intention tremor, cerebellar gait ataxia, parkinsonism, working memory impairment, and frontal executive dysfunction. FXTAS occurs predominantly in men over age 50 years.","Chromosomal abnormality"
"H02386","Phaeohyphomycosis","Phaeohyphomycosis is an infectious disease caused by many species of dematiaceous fungi. It is associated with a wide range of inflammatory responses. Over 100 species and 60 genera of dematiaceous fungi have been confirmed as agents of phaeohyphomycosis. They are commonly found in the soil and are generally distributed worldwide. Exposure is thought to be from inhalation or minor trauma.","Infectious disease"
"H01503","Zygomycosis","The class Zygomycetes is divided into two orders, Mucorales and Entomophthorales. These two orders produce different infections. Genera from the order Mucorales cause an angioinvasive infection called mucormycosis. Mucormycosis can present as rhinocerebral, pulmonary, disseminated, cutaneous and gastrointestinal involvement. Genera from the order Entomophthorales cause a chronic subcutaneous infection called entomophthoramycosis in immunocompetent patients.","Infectious disease"
"H00617","Desmosterolosis","Desmosterolosis is a very rare disorder of cholesterol biosynthesis. Multiple congenital malformations including developmental delay, brain malformations, skeletal anomalies, and facial deformities are caused by impaired cholesterol synthesis due to mutations in the enzyme 24-dehydrocholesterol reductase (DHCR24).","Congenital malformation"
"H02140","Boucher-Neuhauser syndrome","Boucher-Neuhauser syndrome (BNS) is a rare syndrome characterized by the triad of early-onset autosomal-recessive cerebellar ataxia (ARCA), hypogonadotropic hypogonadism, and chorioretinal dystrophy. Gait ataxia in BNS has been typically reported between the first and third decades of life; later ages of onset are rare. BNS has recently been linked to autosomal-recessive mutations in the PNPLA6 gene.","Nervous system disease"
"H02372","Cystoisosporiasis","Cystoisosporiasis is a human enteritis caused by Cystoisospora belli. Cystoisospora belli is an obligate intracellular protozoa in phylum Apicomplexa. The transmission is through ingestion of sporulated oocysts contaminating food or water. It can cause severe diarrhea in immunocompromised patients, with a high rate of recurrence and risk of dissemination.","Infectious disease"
"H00425","Lysosomal cysteine protease deficiencies","Defects in lysosomal cysteine proteases (Cathepsins) are autosomal recessive lysosomal storage diseases. To date only following two human diseases cathepsin deficiencies have been described, though there are eleven lysosomal cystein proteases. Deficiency of cathepsin C leads to Papillon-Lefevre syndrome characterized by palmoplantar hyperkeratosis and severe early onset periodontitis. Deficiency of cathepsin K leads to pycnodysostosis characterized by osteosclerosis and short stature. Recent findings suggest a more expanded role for cathepsins in human biology.","Inherited metabolic disease; Congenital malformation"
"H00041","Kaposi sarcoma","Kaposi sarcoma (KS) is an angioproliferative disease classified into classic KS, endemic KS, iatrogenic KS, and HIV-associated KS (HIV-KS), however, share the same histological traits and are all associated with infection by the human herpesvirus 8 (HHV8; also known as KSHV). Evidence indicates that KS progression occurs upon the deregulated expression of anti-apoptotic genes (Bcl-2), oncogenes (c-myc, c-int, ras) and oncosuppressor genes (TP53), and is associated with the long-lasting expression of HHV8 latency genes (LANA, v-cyc D, v-FLIP, Kaposin). All these genes are, in fact, expressed or altered in most KS spindle cells in the nodular-late stage of KS. Bcl-2 acts as a major KS progression factor, and TP53 and c-myc may also have a role in disease progression. HHV8 latency gene products may be involved in KS progression due to their capability of promoting cell growth by direct effects or antiapoptotic effects.","Cancer"
"H01193","Familial tumoral calcinosis","Familial tumoral calcinosis (FTC) refers to a group of disorders inherited in an autosomal recessive fashion, distinguished by the development of ectopic and vascular calcified masses that occur in settings of hyperphosphatemia (hFTC) and normophosphatemia (nFTC). hFTC is characterized by increased re-absorption of phosphate through the renal proximal tubule, resulting in elevated phosphate concentration and deposition of calcified deposits in cutaneous and subcutaneous tissues, occasionally, in visceral organs. hFTC has been shown to result from mutations in three genes: fibroblast growth factor-23 (FGF23), KL encoding Klotho, and GALNT3, which encodes a glycosyltransferase responsible for FGF23 O-glycosylation; defective function of any one of these three proteins results in hyperphosphatemia and ectopic calcification. nFTC is characterized by absence of metabolic abnormalities. nFTC has been found to be associated with absence of functional SAMD9, a putative tumor suppressor and anti-inflammatory protein.","Inherited metabolic disease"
"H00273","Pycnodysostosis","Pycnodysostosis is an autosomal recessive skeletal disorder caused by deficiency of cathepsin K in the metabolism of the skeletal system, causing defects in bone resorption and bone remodeling. Pycnodysostosis is characterized by short stature, osteosclerosis, acroosteolysis, separated cranial sutures with open fontanelles, bone fragility, and loss of mandibular angle.","Inherited metabolic disease; Lysosomal storage disease"
"H01301","Hemorrhagic destruction of the brain, subependymal calcification, and cataracts","Hemorrhagic destruction of the brain, subependymal calcification, and cataracts is an autosomal-recessive syndrome with severe hemorrhagic destruction of the brain as a cardinal feature. A mutation in JAM3 that encodes tight-junction protein causes this syndrome.","Nervous system disease"
"H01133","Reynolds syndrome","Reynolds syndrome is a rare disease associating primary biliary cirrhosis (PBC) and systemic scleroderma (SSc). It is typically classified as an autoimmune disorder since there are specific autoantibodies associated with both facets of the disease (antimitochondrial antibodies for PBC and anticentromere/antitopoisomerase for SSc), and suggestive microscopical abnormalities in the skin and liver. A mutation in the Lamin B receptor gene has been discovered in the white blood cells, suggesting that nuclear signalling defects could be a cause in Reynolds syndrome.","Skin and connective tissue disease; Digestive disease"
"H01557","Hepatic angiosarcoma","Angiosarcoma represents 1 to 2% of soft tissue tumors. It originates from endothelial cells of small blood vessels and may affect a variety of organs, including the retroperitoneum, skeletal muscle, subcutis, liver, heart and breast. Primary hepatic angiosarcomas (HAS) are much rare tumors, with worse prognosis compared with other angiosarcomas. HAS has been found to be caused by occupational exposure to vinyl chloride (VC) monomer since 1970, and the number of VC-associated HAS cases reported up to the end of 1998 was 197 worldwide. Exposure of VC connects with a series of mechanistic events leading to carcinogenic outcome; mutations of K-ras and p53 are also detected.","Cancer"
"H00485","Robinow syndrome","Robinow syndrome (RS) is a rare genetically heterogeneous condition characterized by hypertelorism, nasal features (large nasal bridge, short upturned nose, and anteverted nares), midface hypoplasia, mesomelic limb shortening, brachydactyly, clinodactyly, micropenis, and short stature. Both autosomal recessive and autosomal dominant inheritance have been described. The phenotypic presentation in both types of RS overlaps; however, subtle variances in the severity of craniofacial, musculoskeletal, cardiovascular, and urogenital characteristics may be present. In general, autosomal recessive RS (RRS) patients have more severe dysmorphology than autosomal dominant RS (DRS), especially in the musculoskeletal system.","Congenital malformation"
"H01765","Eosinophilic sinusitis","Eosinophilic chronic rhinosinusitis (ECRS) is an inflammatory pathological condition of the nose and paranasal sinuses. Chronic rhinosinusitis (CRS) is a common disease worldwide, and CRS may be divided into ECRS and non-ECRS subtypes based on the presence of tissue eosinophilic infiltration or not. There are significant geographic and ethnic differences in the tissue eosinophilic infiltration, which is predominant in Western white patients and less common in East Asians, despite an increasing tendency for its prevalence in East Asia countries. ECRS commonly demonstrates more severe symptoms, polyp diseases with a higher incidence of bilateral polyps and sinonasal diseases on computed tomography, and the increase in blood eosinophils. Patients with ECRS exhibit clinical characteristics that include long term nasal congestion, mucus production, olfactory disturbances, bilateral nasal polyposis, and intermittent acute exacerbation of secondary bacterial infections. Since there is no approved medication to treat patients with ECRS with nasal polyps completely, surgery is often needed to clear the sinonasal passage, and repeated endoscopic sinus surgery (ESS) is often required. The effectiveness of low-dose, long-term erythromycin treatment (macrolide therapy) was reported for the treatment of CRS in Japan.","Immune system disease; Respiratory disease; Skin and connective tissue disease"
"H00471","Split-hand/foot malformation","Split hand/foot malformation (SHFM) is a congenital limb malformation characterized by median clefts of hands and foot. Disrupted formation of the apical ectodermal ridge during development results in central ray deficiency in SHFM patients.","Congenital malformation"
"H02326","Keipert syndrome","Keipert syndrome is a rare, X-linked disorder characterized by craniofacial and digital abnormalities and variable learning difficulties and sensorineural deafness. It has been reported that pathogenic variants in GPC4 cause this disease.","Congenital malformation"
"H02114","Spastic paraplegia, optic atrophy, and neuropathy","Spastic paraplegia, optic atrophy, and neuropathy (SPOAN) is an autosomal recessive neurodegenerative disorder clinically defined by congenital optic atrophy, progressive spastic paraplegia with onset in infancy, and progressive motor and sensory axonal neuropathy. A mutation in KLC2 gene has been reported to be responsible for the SPOAN phenotype.","Nervous system disease"
"H01791","Smith-Magenis syndrome","Smith-Magenis syndrome (SMS) is a complex neurobehavioral disorder caused by haploinsufficiency of the retinoic acid-induced 1 (RAI1) gene on chromosome 17p11.2. SMS is characterised by intellectual disability, self-injurious behaviours, sleep disturbance, obesity, and craniofacial and skeletal anomalies. Most SMS features are due to RAI1 haploinsufficiency, while the variability and severity of the disorder are modified by other genes in the 17p11.2 region.","Chromosomal abnormality"
"H00643","Tooth and nail syndrome","Witkop syndrome, also known as tooth and nail syndrome, is a form of ectodermal dysplasia manifested by hypodontia and nail dysplasia. Several teeth are congenitally missing and nails are spoon-shaped and easily broken. Mutations are identified in MSX1 gene.","Congenital malformation"
"H00227","Congenital amegakaryocytic thrombocytopenia","Congenital amegakaryocytic thrombocytopenia (CAMT) is an autosomal recessive bone marrow failure syndrome, characterized by thrombocytopenia due to defective megakaryocytopoiesis. The disorder is induced by defective expression or function of the thrombopoietin (THPO) receptor caused by mutations in the MPL gene.","Hematologic disease"
"H00015","Malignant pleural mesothelioma","Malignant mesothelioma (MM) is a rare but very aggressive tumor that arises from mesothelial cells lining the pleural, peritoneal and pericardial cavities. Malignant pleural mesothelioma (MPM) is the most common type, accounting for about 70% of all MM cases. Past asbestos exposure represents the major risk factor for MPM, as the link between asbestos fibres and MPM has been largely proved by epidemiological and experimental studies. Recently, simian virus 40 (SV40) has been implicated in the aetiology of MPM. The accumulation of numerous clonal chromosomal deletions in most MMs suggests a multistep process of tumorigenesis, characterized by the loss and/or inactivation of multiple tumor suppressor genes (TSGs). Cytogenetic and loss of heterozygosity (LOH) analyses of MMs have demonstrated frequent deletions of specific sites within chromosome arms 1p, 3p, 6q, 9p, 13q, 15q, and 22q. Furthermore, TSGs within two of these regions, i.e., p16/CDKN2A-p14ARF at 9p21 and NF2 at 22q12, are frequently altered in MMs. Mutations of the p53 gene (TP53) are occasionally observed in MMs.","Cancer"
"H00829","Multiple familial trichoepithelioma","Multiple familial trichoepithelioma is a benign epidermal tumor characterized by grouped nodules and papules on the face. The lesions are derived from immature hair follicles. It is inherited in autosomal dominant fashion and is related to Brooke-Spiegler syndrome and Familial cylindromatosis.","Skin and connective tissue disease"
"H00688","Familial advanced sleep phase syndrome","Familial advanced sleep phase syndrome (FASPS) is characterized by a stable sleep schedule with a 4-hour advance than the conventional or desired time. FASPS is associated with mutations in PER2, whose level oscillates with a nearly 24 hour period. Recently, it has been reported that FASPS is also caused by mutations in CSKD1D gene and PER3 gene.","Nervous system disease"
"H01568","3C syndrome","The 3C syndrome, also known as Ritscher-Schinzel syndrome, is a rare, presumably autosomal recessive syndrome characterized by craniofacial, cerebellar, and cardiac anomalies. Cardiac manifestations include ventricular septal defect, atrial septal defect, tetralogy of Fallot, double outlet right ventricle, hypoplastic left heart, aortic stenosis, pulmonic stenosis, and other valvular anomalies. Central nervous system anomalies include Dandy-Walker malformation, cerebellar vermis hypoplasia, and enlargement of the cisterna magna. Craniofacial abnormalities seen are cleft palate, ocular coloboma, prominent occiput, low-set ears, hypertelorism, down-slanting palpebral fissures, depressed nasal bridge, and micrognathia. The phenotypic manifestations can vary and cardiac and cerebellar manifestations are not always present. A recent study identified homozygous sequence variants affecting the KIAA0196 gene, which encodes the WASH (Wiskott-Aldrich Syndrome Protein and SCAR Homolog) complex protein strumpellin as causal to a form of 3C syndrome. Another study showed that a missense variant in CCDC22 is associated with a form of X-linked intellectual disability with features of 3C syndrome.","Congenital malformation"
"H01930","Au-Kline syndrome","Au-Kline syndrome is a new syndrome due to loss-of-function variants in the heterogeneous nuclear ribonucleoprotein K gene (HNRNPK). Patients present with intellectual disability, facial dysmorphism and skeletal/connective tissue abnormalities. Facial dysmorphism and multiple congenital anomalies overlap with Kabuki syndrome.","Congenital malformation"
"H00816","Agenesis of the corpus callosum with peripheral neuropathy","Agenesis of the corpus callosum with peripheral neuropathy (ACCPN) is a severe neurodegenerative disorder that is transmitted as an autosomal recessive trait. It is associated with mental retardation, progressive peripheral neuropathy caused by axonal degeneration, and complete or partial agenesis of the corpus callosum. ACCPN is found in French Canadian population and could be resulted from a single founder mutation.","Nervous system disease"
"H00218","Cystic fibrosis","Cystic fibrosis (CF) is an autosomal recessive disorder of the exocrine glands caused by mutation of CFTR gene which encodes an ABC transporter for salt homeostasis. CF is a common lethal single-gene disorder in Caucasians with an incidence of 1 in 1500 to 1 in 6500, whereas it is rare among Orientals (1:90000). The common clinical features are chronic pulmonary infection with Pseudomonas aeruginosa, respiratory distress, and pancreatic insufficiency. A part of patients with CF present with a gastrointestinal blockage known as meconium ileus.","Inherited metabolic disease; Digestive disease; Respiratory disease"
"H02319","IMAGE syndrome","IMAGE syndrome (intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita and genital anomalies) is an autosomal dominant undergrowth developmental disorder with life-threatening consequences and caused by mutations in CDKN1C.","Endocrine and metabolic disease"
"H00012","Polycythemia vera","Polycythemia vera (PV) is a clonal myeloproliferative disease characterized by an erythroid dominant trilineage proliferation of hematopoietic precursor cells. PV belongs to the family of chronic myeloproliferative disorders (MPD), which includes hematological diseases that share clinical and biological similarities, such as a hematopoietic stem cell origin: PV, essential thrombocythemia (ET), primary myelofibrosis (PMF), chronic myeloid leukemia (CML), some types of hypereosinophilic syndrome (HES), systemic mast cell disease (SMD) and other rare disorders. Recently, a specific point mutation in the Janus kinase 2 (JAK2) gene was described in a majority of PV patients and thus constitutes a sensitive diagnostic marker for the disease.","Cancer"
"H00220","Factor V deficiency","Factor V deficiency is an autosomal recessive hemorrhagic disorder, which is identified as an inherited resistance to the anticoagulant function of activated protein C.","Hematologic disease"
"H02113","Infantile cerebellar-retinal degeneration","Infantile cerebellar-retinal degeneration (ICRD) is a disorder characterized by profound psychomotor retardation and progressive visual loss, including optic nerve and retinal atrophy. Recently, missense mutations in a TCA enzyme, mitochondrial aconitase (ACO2), catalysing interconversion of citrate into isocitrate, have been reported in a sibship with infantile-onset encephalopathy, optic nerve involvement, and cerebellar atrophy.","Nervous system disease"
"H01796","Uncombable hair syndrome","Uncombable hair syndrome (UHS) is a rare anomaly of the hair shaft characterized by dry, frizzy, spangly, and often fair hair that is resistant to being combed flat. Both simplex and familial UHS-affected cases with autosomal dominant as well as recessive inheritance have been described. Recently, the identification of causative mutations were reported. No proven therapy exists. In the typical case, improvement may occur over time and spontaneous regression has been reported. Scanning electron microscopy of hair samples provides definitive evidence for diagnosis of clinically suspected UHS and eliminates other hair abnormalities from the differential diagnosis.","Skin and connective tissue disease"
"H00644","Ectodermal dysplasia/skin fragility syndrome","Ectodermal dysplasia/skin fragility syndrome is a very rare genodermatosis that develops skin fragility with tearing and blisters and congenital ectodermal dysplasia. Progressive keratosis of the palms and soles is always seen in the patients. This conditon is caused by mutations in PKP1, a desmosomal plaque-associated protein.","Congenital malformation"
"H00476","Multiple epiphyseal dysplasia","Multiple epiphyseal dysplasia (EDM) is a genetically heterogeneous condition where ossification of epiphyses is delayed. Mutations causing MED have been identified in COMP, DTDST, MATN3, COL9A1, COL9A2, and COL9A3. Mutations in the COL2A1 gene cause multiple epiphyseal dysplasia with myopia and conductive deafness (EDMMD).","Congenital malformation"
"H02321","Early-onset myopathy, areflexia, respiratory distress, and dysphagia","Early-onset myopathy, areflexia, respiratory distress, and dysphagia (EMRDD) is an autosomal recessive myopathy characterized by severe weakness, respiratory impairment, scoliosis, joint contractures, and an unusual features on muscle biopsy. Mutations in MEGF10, a regulator of satellite cell myogenesis, cause EMRDD.","Musculoskeletal disease"
"H01762","Muscle glycogen storage disease","Glycogen storage diseases (GSD) are inherited metabolic disorders of glycogen metabolism. They are divided into types 0 to XV, according to enzyme or transporter deficiency and organ distribution. Disorders of glycogen degradation may affect primarily the liver, the muscle, or both. GSD has been known to mainly be a liver disease with the exception of Pompe (GSD II), McArdle (GSD V), or Tarui (GSD VII) diseases. Recently, however, various muscular disorders involving different types of muscles have been described to be caused by defective glycogen metabolism. In the Muscle GSDs, the consequence of a block in skeletal muscle glycogenolysis, or in the glycolysis, is an impairment of muscular performance, owing to an increase in glycogen storage that disrupts contractile function and/or a reduced substrate turnover, which inhibits skeletal muscle ATP production.","Inherited metabolic disease; Musculoskeletal disease"
"H01550","Bunyamwera fever","Bunyamwera fever is an infectious disease caused by Bunyamwera virus (BUNV), an orthobunyavirus in the order Bunyavirales of -ssRNA viruses, and transmitted by Aedes and Anopheles mosquitoes. BUNV was first isolated in 1943 in Uganda.","Infectious disease"
"H00482","Brachydactyly","Brachydactyly (BD) comprises hereditary limb malformations characterized by apparent shortening of digits. Bone dysostosis is seen in middle phalanges in type A; distal phalanges in type B; distal phalanx of the thumb in type D; metacarpals in type E. Type C characterized by shortening of multiple phalanges and hyperphalangy. Brachydactyly is caused by improper development of the bones.","Congenital malformation"
"H01134","Rhabdoid predisposition syndrome","Rhabdoid predisposition syndrome (RPS) is familial cases of highly malignant, aggressive, embryonal neoplasms manifested in early infancy and childhood that may originate from virtually any tissue, generally resulting in atypical teratoid rhabdoid tumors (AT/RTs) in the central nervous system and malignant rhabdoid tumors in the kidney or retroperitoneum. The vast majority demonstrate biallelic somatic inactivation of the SMARCB1 tumor suppressor within tumor cells. Mutations in SMRCA4 gene have also been identified.","Cancer"
"H01908","Carey-Fineman-Ziter syndrome","Carey-Fineman-Ziter syndrome (CFZS) is a rare multiple congenital anomalies syndrome defined by a combination of Pierre Robin syndrome and Moebius syndrome, associated with hypotonia and various other malformations. Pierre Robin syndrome is characterized by a triad of micrognathia, glossoptosis and a U-shaped cleft palate. Moebius syndrome is characterized by congenital palsy of the 6th and 7th cranial nerves. It has been reported that autosomal recessive mutations in MYMK cause CFZS. Myomaker, encoded by MYMK, is expressed on the cell surface of myoblasts during fusion. Fusion of myoblasts is essential for the formation of multi-nucleated muscle fibres.","Congenital malformation"
"H01306","FRA12A mental retardation","FRA12A mental retardation is a rare form of mental retardation caused by expansion of CGG repeat. This repeat is in the 5' untranslated region of the gene DIP2B. It has been suggested that deficiency of DIP2B, a brain-expressed gene, may mediate the neurocognitive problems associated with FRA12A.","Mental and behavioural disorder"
"H00449","Oculodentodigital dysplasia","Oculodentodigital dysplasia (ODDD) is an inherited disorder involving characteristic facial appearance and abnormalities of eyes, teeth, and limbs. The disease is inherited in both an autosomal dominant and recessive fasion. ODDD is caused by mutations in the gap junction alpha 1 gene.","Congenital malformation"
"H00811","Distal arthrogryposis","Distal arthrogryposis (DA) are a distinct group of syndromes with congenital contractures primarily involving the hands and feet, which often are associated with abnormal facies. To date, 10 different DA syndromes have been characterized and classified. DA2A and DA2B are also referred to as Freeman-Sheldon syndrome and Sheldon-Hall syndrome, respectively. The most of causative genes have implicated proteins of the contractile apparatus of the fast-twitch myofibers.","Congenital malformation"
"H01339","Asymptomatic bacteriuria","The term asymptomatic bacteriuria is generally used to distinguish colonization from infection and to emphasize that the presence of bacteria at mucosal surfaces does not always cause symptoms and tissue damage. Asymptomatic bacteriuria has been attracting attention as a model to study mechanisms underlying the development of commensalism. Escherichia coli strain 83972 was isolated from the urine of a Swedish patient who was colonized for at least 3 years without displaying clinical signs of a urinary tract infection.","Infectious disease"
"H01937","Multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly","Multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly (MARCH) is an autosomal-recessive lethal fetal ciliopathy caused by loss-of-function mutations in CEP55. Hydranencephaly is a congenital anomaly leading to replacement of the cerebral hemispheres with a fluid-filled cyst.","Congenital malformation"
"H00672","Pseudofolliculitis barbae","Pseudofolliculitis barbae is a common skin disorder occurring predominantly in males of African origin, characterized by acneiform papules and pustules that result in keloidal scarring localized to the facial and submental regions. It is caused when highly curved hair shafts repenetrate the skin. A single nucleotide polymorphism in KRT75, which leads to a disruptive Ala12Thr substitution, has been demonstrated in the disease.","Skin disease"
"H02125","Cardiac conduction disease with dilated cardiomyopathy","Cardiac conduction disease with dilated cardiomyopathy (CCDD) is an autosomal dominant syndrome characterized by conduction system disease, atrial tachyarrhythmia and dilated cardiomyopathy. TNNI3K mutation in this disease has been reported. The TNNI3K gene encodes the protein TNNI3 interacting kinase which is located at the sarcomere Z disc. It may play a crucial role in cardiac physiology.","Cardiovascular disease"
"H02317","SERKAL syndrome","SERKAL syndrome is an autosomal recessive syndrome that consists of female to male sex reversal and renal, adrenal, and lung dysgenesis and is associated with additional developmental defects. It is caused by loss-of-function mutations in WNT4.","Reproductive system disease"
"H00440","Rett syndrome","Rett Syndrome is a severe neurological disorder found almost exclusively in girls. It is characterized by acquired microcephaly, communication dysfunction, psychomotor regression, seizures and stereotypical hand movements. Mutations in MECP2 are identified in most patients with classic Rett syndrome. Recently, mutations in FOXG1 gene have been shown to cause congenital variant of Rett syndrome.","Nervous system disease"
"H01592","Medullary thyroid cancer","Medullary thyroid carcinoma (MTC) is a malignant tumor originating from thyroid parafollicular C cells and accounts for only <5% of thyroid cancers, but it causes a disproportionate number of thyroid cancer deaths due to its more aggressive clinical behavior compared with well-differentiated papillary and follicular thyroid carcinomas. A subset of MTC cases is hereditary and due to germline mutations in the RET tyrosine kinase receptor gene. Somatic mutations in either RET or RAS are also present in most sporadic tumors. In MTC, RET mutations lead to substrate-independent dimerization of the receptor causing constitutive activation, unrestricted signaling, and ultimately, cancer.","Cancer"
"H00024","Prostate cancer","Prostate cancer constitutes a major health problem in Western countries. It is the most frequently diagnosed cancer among men and the second leading cause of male cancer deaths. The identification of key molecular alterations in prostate-cancer cells implicates carcinogen defenses (GSTP1), growth-factor-signaling pathways (NKX3.1, PTEN, and p27), and androgens (AR) as critical determinants of the phenotype of prostate-cancer cells. Glutathione S-transferases (GSTP1) are detoxifying enzymes. Cells of prostatic intraepithelial neoplasia, devoid of GSTP1, undergo genomic damage mediated by carcinogens. NKX3.1, PTEN, and p27 regulate the growth and survival of prostate cells in the normal prostate. Inadequate levels of PTEN and NKX3.1 lead to a reduction in p27 levels and to increased proliferation and decreased apoptosis. Androgen receptor (AR) is a transcription factor that is normally activated by its androgen ligand. During androgen withdrawal therapy, the AR signal transduction pathway also could be activated by amplification of the AR gene, by AR gene mutations, or by altered activity of AR coactivators. Through these mechanisms, tumor cells lead to the emergence of androgen-independent prostate cancer.","Cancer"
"H00818","Birt-Hogg-Dube syndrome","Birt-Hogg-Dube syndrome is an autosomal dominant condition characterized by skin fibrofolliculomas, multiple pulmonary cysts, and renal cancer. Skin lesions usually appear after the age of 20 years with multiple white papules in the midface. The disease is caused by mutations in the FLCN gene coding for folliculin.","Other disease"
"H00216","Congenital adrenal hyperplasia","Congenital adrenal hyperplasia (CAH) is a group of monogenic autosomal recessive disorders due to an enzyme deficiency in steroid biosynthesis. All the adrenal hyperplasia syndromes are examples of mixed hypo- and hyperadrenocorticism.","Endocrine and metabolic diseases"
"H01102","Pituitary adenomas","Pituitary adenomas are an important and frequently occurring form of intracranial tumor. They are usually benign but can give rise to severe clinical syndromes due to hormonal excess, or to visual/cranial disturbances due to mass effect. The tumor can be clinically nonfunctioning or hormone secreting. Among the latter, prolactin (PRL) and growth hormone (GH)-secreting adenomas are the most common. The majority of pituitary adenomas arise sporadically, although a subset occurs as component tumors of well-characterized familial cancer syndromes, such as multiple endocrine neoplasia type 1 (MEN1), Carney complex (CNC), and MEN1-like syndrome (MEN4).","Endocrine and metabolic disease"
"H01330","Brazilian purpuric fever","Brazilian purpuric fever (BPF) is a pediatric disease caused by Haemophilus influenzae biogroup aegyptius (H. aegyptius) and is often fatal. This disease is characterized by purulent conjunctivitis and subsequent acute onset of nausea, vomiting, hemorrhagic skin lesions, fever, prostration, and shock. Vascular destruction is a distinctive trait.","Infectious disease"
"H00686","Manitoba oculotrichoanal syndrome","Manitoba oculotrichoanal (MOTA) syndrome is a rare condition characterized by aberrant anterior hairline, upper-eyelid colobomas, hypertelorism, cryptophthalmos, a bifid or notched nose, and anal anomalies. MOTA syndrome is inherited in an autosomal recessive manner.","Congenital malformation"
"H01754","Crouzon syndrome","Crouzon syndrome (CS) is an autosomal dominant disorder characterized by generalized craniosynostoses, maxillary hypoplasia, widely spaced but shallow orbits with prominent globes. Heterozygous mutations of FGFR2 cause three classical craniosynostosis syndromes, Apert, Crouzon and Pfeiffer. Crouzon syndrome is usually the mildest of the FGFR2-associated disorders and the clinical diagnosis is suggested by the combination of characteristic facies and absence of major abnormalities of the hands and feet. It has also been reported that a mutation of FGFR3 gene causes Crouzon syndrome with acanthosis nigricans.","Congenital malformation"
"H01566","Beriberi","Beriberi is the classical syndrome caused by thiamine (vitamin B1) deficiency. Beriberi has two major clinical manifestations, dry beriberi characterized by neurologic manifestations that include peripheral neuropathy and acute encephalopathy, and wet beriberi with cardiovascular involvement including high cardiac output heart failure. Rarely, a fulminant or pernicious variant, termed Shoshin beriberi may occur, and is characterized by cardiovascular collapse. Appropriate management of this form is mandatory since thiamine supplementation leads to rapid recovery while untreated forms are fatal.","Endocrine and metabolic disease"
"H00229","Sickle cell anemia","Sickle cell anaemia (SCA) is a recessive genetic disease caused by a single-point mutation in the beta globin gene in codon 6 (Glu6Val) that specifies one of the chains of haemoglobin. The disease is characterized by a chronic haemolytic anaemia with the sickle cells which show abnormal morphology due to the damage of the membrane skeletons and agglutinate under deoxygenated conditions.","Hematologic disease"
"H00827","Brooke-Spiegler syndrome","Brooke-Spiegler syndrome is an inherited disease characterized by multiple tumors of tissues derived from folliculo-sebaceous-apocrine unit, including cylindromas, trichoepitheliomas, and/or spiradenomas. It is an autosomal dominant condition.","Skin and connective tissue disease"
"H02328","Sifrim-Hitz-Weiss syndrome","Sifrim-Hitz-Weiss syndrome is characterized by developmental delay, intellectual disability, hearing loss, macrocephaly, distinct facial dysmorphisms, palatal abnormalities, ventriculomegaly, and hypogonadism as well as additional findings such as bone fusions. It has been reported that de novo mutations in CHD4 cause this disease. CHD4 is a core component of the NuRD complex, which possesses both chromatin remodeling and histone deacetylation activities.","Congenital malformation"
"H01559","Oropharyngeal cancer","Oropharyngeal cancer is a generic term that includes tumors arising within the anatomic confines of the posterior pharyngeal wall, soft palate, tonsillar region and posterior one-third (base) of the tongue. The vast majority of these tumors (>95%) includes squamous cell carcinomas of mucosal origin. Oropharyngeal squamous cell carcinomas (OPSCCs) are traditionally categorized as head and neck squamous cell carcinoma (HNSCC). High-risk human papillomavirus (HR-HPV) is now recognised as a causative agent in a subset of OPSCCs. HPV-driven OPSCC and tobacco- and alcohol-related OPSCC are biologically distinct entities. In the former, p53 and pRb are both inactivated at the protein level by, respectively, E6 and E7 viral oncoproteins. The majority of HPV-negative tumors, instead, harbor mutations in the TP53 gene, an increased epidermal growth factor receptor (EGFR) gene copy number and higher EGFR expression by immunohistochemistry (IHC).","Cancer"
"H01901","Barrett esophagus","Barrett esophagus (BE) is the premalignant lesion of esophageal adenocarcinoma (EAC) defined as specialized intestinal metaplasia (SIM) of the tubular esophagus. According to some studies, the incidence of the esophageal adenocarcinoma in patients with BE is of about 0.5% per year. The major pathogenetic factor in the development of BE is represented by the gastroesophageal reflux disease. BE is characterized by the replacement of the normal squamous epithelium with the columnar epithelium, when the healing of the lesion occurs. Because only a minority of patients (around 10-15%) with gastroesophageal reflux disease have BE, additional factors that play important roles in determining the development of BE must concur. Another frequent association with BE, is represented by nitrate, an increased age, Caucasian race, male sex and hiatal hernia. Recently, it has been reported that mutations in MSR1, ASCC1, and CTHRC1 are associated with this disease.","Digestive system disease"
"H01561","Chiari malformation","Chiari malformations, also known as Arnold-Chiari syndrome, is a group of syndromes consisting of different kinds of pathologic conditions of the posterior fossa development. They are congenital in most cases, caused by structural defects in the brain spinal cord which may involve genetic mutations or lack of proper vitamins or nutrients in the maternal diet. Less frequently, Chiari malformations are acquired after birth. Causes of acquired Chiari malformations involve injuries, exposure to harmful substances, infections. More rarely, chronic subdural hematoma can be the cause of progressive caudal descent of the cerebellar tonsils. Chiari malformations were classified by Hans Chiari in 1891, into four groups. Chiari malformation type I (CM I), the most frequent of Chiari malformations, is characterized by the inferior displacement of cerebellar tonsillas through the foramen magnum. This leads to different symptoms and clinical features, such as headaches, syringomyelia, and hydrocephalus. CM II is characterized by displacement of the parts of the inferior vermis, pons, and medulla oblongata together with elongation of the fourth ventricle. Most cases are associated with myelomeningocele. CM III is characterized by an occipital or cervical encephalocele along with the intracranial abnormalities seen with CM II malformation and a wide foramen magnum. It causes severe neurological defects. CM IV is characterized by marked cerebellar hypoplasia or aplasia.","Congenital malformation"
"H00681","Acne inversa","Acne inversa (AI), also known as hidradenitis suppurativa, is a chronic inflammatory disorder of hair follicles involving the apocrine gland-bearing areas of the body. Its characteristic features include recurrent formation of painful skin abscesses, fistulating sinuses, and disfiguring scars.","Skin disease"
"H01753","Antley-Bixler syndrome","Antley-Bixler syndrome (ABS) is a rare craniosynostosis syndrome characterized by radiohumeral synostosis. There is a wide spectrum of anomalies seen in ABS. Other features include midface hypoplasia, choanal stenosis or atresia, and multiple joint contractures. Two genetically distinctive forms have been observed. Type 1 ABS involves mutations in the FGFR2 gene without impairment of steroidogenesis. Type 1 ABS patients are with the most severe skeletal abnormalities but normal genitalia. Type 2 ABS involves mutations in the gene encoding cytochrome P450 oxidoreductase (POR), an enzyme which plays a direct role in steroidogenesis. Type 2 ABS is an autosomal recessive disorder, and it is associated with abnormal genitalia in both sexes due to impaired steroidogenesis. Mortality has been reported to be as high as 80% in the neonatal period, primarily due to airway compromise, and prognosis improves with increasing age.","Congenital malformation"
"H01337","Laribacter hongkongensis infection","Laribacter hongkongensis is a facultatively anaerobic, nonsporulating, gram-negative, spiral rod-shaped bacterium belongs to the Neisseriaceae family of the subclass of Proteobacteria. L. hongkongensis was isolated from the blood and empyema of a cirrhotic patient and associated with freshwater fish-borne gastroenteritis and traveler's diarrhea.","Infectious disease"
"H01105","Cranio-lenticulo-sutural dysplasia","Cranio-lenticulo-sutural dysplasia (CLSD) is a rare autosomal recessive syndrome characterized by late-closing fontanels, sutural cataracts, facial dysmorphisms, and skeletal defects. CLSD is caused by a SEC23A mutation leading to abnormal endoplasmic-reticulum-to-Golgi trafficking.","Congenital malformation"
"H01939","Glycogen storage disease type I","Glycogen storage disease type I (GSD-I), also known as von Gierke disease, is an autosomal recessive disorder caused by a deficiency in microsomal glucose-6-phosphatase (G6Pase) activity. There are four distinct subgroups of this disorder, Ia, Ib, Ic, and Id. GSD-Ia is caused by mutations in the G6Pase gene. Clinical manifestations include short stature, hepatomegaly, hypoglycemia, hyperuricemia, and lactic acidemia. GSD-Ib, Ic, and Id result from deficient activity of the phosphate/ pyrophosphate transporter of G6Pase complex and is associated with neutropenia as well as hepatomegaly and hypoglycaemia.","Inherited metabolic disease"
"H00211","Hemochromatosis","Hereditary hemochromatosis (HFE) is an autosomal recessive iron metabolism disorder characterized by increased intestinal iron absorption, which leads to progressive accumulation of iron in the body.","Inherited metabolic disease"
"H00023","Testicular cancer","Testicular germ cell tumor (TGCT) comprises about 98% of all testicular neoplasms and is thereby the most common malignancy among young males. Overall, three different entities of TGCT can be distinguished: teratomas and yolk sac tumors of newborns and infants, seminomatous and nonseminomatous germ cell tumors of adolescents and young adults, and spermatocytic seminoma of elderly men. Recent studies of TGCTs have suggested that overexpression of cyclin D2 is a very early, possibly the oncogenic, event in GC tumorigenesis.","Cancer"
"H02310","Renal tubular acidosis","Renal tubular acidosis (RTA) is characterized by metabolic acidosis, a severe disturbance of extracellular pH homeostasis, due to renal impaired acid excretion. RTA can be subcategorized into different disorders. Distal RTA (type 1) arises when the collecting duct fails to remove excess acid into the urine. Proximal RTA (type 2) is caused by an impairment of bicarbonate reabsorption in the proximal tubules. RTA type 3 is a mixed type that shares the features of both proximal and distal lesions. RTA type 4 is a heterogeneous group of disorders associated with hyperkalemia due to aldosterone deficiency or impairment in aldosterone molecular signaling.","Urinary system disease"
"H00447","HEM skeletal dysplasia","Hydrops ectopic calcification-moth-eaten (HEM) or Greenberg skeletal dysplasia is a lethal chondrodystrophy characterized by fetal hydrops, short limbs, and abnormal chondro-osseous calcification. It is inherited as an autosomal recessive trait. Homozygous mutation in LBR is the cause of HEM/Greenberg skeletal dysplasia.","Congenital malformation"
"H01595","Cutaneous lupus erythematosus","Cutaneous lupus erythematosus (CLE) is the skin-related form of lupus erythematosus (LE), with a broad spectrum of clinical manifestations and a variable course. CLE is a frequent finding in patients with systemic lupus erythematosus (SLE) and can also exist as a single entity without associated systemic autoimmunity (LE-specific skin disease). Despite ongoing research into the cause of CLE, it remains unclear how CLE relates to SLE pathogenesis. LE-specific skin disease includes the subtypes of CLE such as acute cutaneous LE (ACLE), subacute cutaneous LE (SCLE), chronic cutaneous LE (CCLE), and intermittent CLE (ICLE). ACLE is characterized by malar rash or maculopapular eruption on sun exposed areas. SCLE characteristically presents as annular or psoriasiform plaques in a photo distribution. CCLE can be further divided into discoid lupus erythematosus (DLE), LE profundus (LEP), chilblain LE (CLE), and LE tumidus (LET). The pathogenesis of CLE is multifactorial and involves genetic predisposition, environmental triggers, and abnormalities in the immune response. It has been reported that many genetic risk factors for CLE involve HLA or interferon-related pathways. Corticosteroids and antimalarials were considered as the most suitable and effective systemic drugs for CLE patients.","Immune system disease; Skin disease"
"H00675","Acrocapitofemoral dysplasia","Acrocapitofemoral dysplasia is an autosomal recessive skeletal dysplasia characterized by short stature with brachydactyly, a narrow thorax, and a relatively large head. Radiographically, cone-shaped epiphyses are present in the hands and hips.","Congenital malformation"
"H02122","Chronic atrial and intestinal dysrhythmia","Chronic atrial and intestinal dysrhythmia, termed CAID syndrome, is a cohesinopathy syndrome characterized by a unique combination of cardiac arrhythmias and intestinal pseudo-obstruction. It has been reported that a single homozygous mutation in SGOL1 predisposes to this generalized co-occurring cardiac and intestinal rhythm phenotype.","Cardiovascular disease; Gastrointestinal disease"
"H01906","Poikiloderma, hereditary fibrosing, with tendon contractures, myopathy, and pulmonary fibrosis","Poikiloderma, hereditary fibrosing, with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP) is a rare autosomal dominant disorder caused by mutations in FAM111B. Clinical manifestations are poikiloderma from early childhood and telangiectasia and pigmentary anomalies especially on the face and sun-exposed areas. Scalp hair, eyelashes, and eyebrows are typically sparse. Tendon contractures especially involve the ankles and feet and cause gait disturbance. The majority of affected individuals develop progressive weakness of the proximal and distal muscles of all four limbs. The majority of affected individuals develop progressive weakness of the proximal and distal muscles of all four limbs. Pulmonary involvement are noted during the second decade of life, and progressive dyspnea and restrictive impairment of lung function were linked to pulmonary fibrosis. Other features are exocrine pancreatic insufficiency, liver impairment, hematologic abnormalities, relative short stature, and cataract.","Skin and connective tissue disease; Musculoskeletal disease; Respiratory disease"
"H01308","Macrocephaly macrosomia facial dysmorphism syndrome","Macrocephaly macrosomia facial dysmorphism syndrome is characterized by overgrowth, learning disability, and dysmorphic features. Mutations in RNF135 cause this syndrome.","Congenital malformation"
"H01798","Autosomal dominant neovascular inflammatory vitreoretinopathy","Autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV) is an inherited autoimmune uveitis and vitreoretinal degeneration characterized by inflammatory cells in the vitreous and anterior chamber, photoreceptor degeneration, vitreous hemorrhages, epiretinal membranes (ERMs), and proliferative iris and retinal neovascularization. It is caused by mutations in CAPN5 gene, encoding an intracellular protease expressed in the retina. In most patients the diagnosis is difficult to make before age 40. Electroretinography can help make the diagnosis in younger individuals in whom the only other sign is the presence of vitreous cells.","Nervous system disease"
"H00478","Prader-Willi syndrome","Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are the most studied genomic-imprinting disorders mapped to chromosome 15q11-q13. Lack of a functional paternal copy of 15q11-q13 causes PWS. Additionally, it has been reported that MECP2 deficiency leads to decreased expression of UBE3A. PWS and AS have characteristic neurologic, developmental, and behavioral phenotypes plus other structural and functional abnormalities. The behavioral and endocrine disorders are more severe in PWS, including obsessive-compulsive symptoms and hypothalamic insufficiency.","Chromosomal abnormality"
"H00820","Bjornstad syndrome","Bjornstad syndrome is an autosomal recessive combination of congenital sensorineural hearing loss and pili torti. It is caused by mutations in BCS1L encoding a protein that is necessary for the assembly of complex III in the mitochondria.","Congenital disorder of metabolism"
"H00843","Hartnup disorder","Hartnup disorder is an autosomal recessive defect of neutral amino acid transport in kidney and intestine accompanied by the symptoms including pellagra-like photo-sensitive skin rash, cerebellar ataxia, and renal aminoaciduria. It is caused by hereditary abnormalities in the neutral amino acid transporter B0AT1 (SLC6A19) in apical membrane.","Inherited metabolic disease"
"H01991","Saethre-Chotzen syndrome","Saethre-Chotzen syndrome (SCS) is an autosomal dominant disease characterized by craniosynostosis, ptosis, and limb and external ear abnormalities. Mutations in the TWIST gene have been extensively reported in SCS. In addition, mutations in FGFR2 was also detected.","Congenital malformation"
"H00629","Acheiropodia","Acheiropodia is an extremely rare, severe congenital malformation caused by LMBR1 deletion. Patients show malformed upper and lower extremities with amputation of distal limbs and aplasia of hands and feet. It is inherited as an autosomal recessive trait.","Congenital malformation"
"H01159","Anterior segment dysgenesis","Anterior segment dysgenesis (ASGD) is a range of developmental defects in structures at the front of the eye. These defects are thought to result from abnormal migration or differentiation of the neural-crest derived mesenchymal cells that give rise to the cornea, iris, and other components of the anterior chamber during eye development. Human ASGD phenotypes are genetically heterogeneous resulting from mutations in different transcription factor genes and a cytochrome enzyme gene. ASGD is sometimes divided into subtypes including aniridia, Axenfeld and Rieger anomalies, iridogoniodysgenesis, Peters anomaly, and posterior embryotoxon.","Congenital malformation"
"H01965","Miyoshi myopathy","Miyoshi myopathy (MM) is a rare autosomal recessive distal myopathy characterized by weakness and atrophy that begins in the posterior compartment muscles of the legs. The onset of symptoms is in young adulthood and often begins with the inability to toe walk. Miyoshi myopathy 1 (MM1) is caused by mutations in the dysferlin gene. Recently, anoctamin 5 (ANO5) was also identified, causing Miyoshi myopathy 3 (MMD3).","Nervous system disease; Musculoskeletal disease"
"H02373","Sarcocystosis","Sarcocystosis is an infectious disease caused by species of Sarcocystis, an intracellular protozoan parasite. Sarcocystis was first reported in 1843. Humans can serve as definitive hosts, with intestinal sarcocystosis for two species acquired from eating undercooked meat: Sarcocystis hominis, from beef, and Sarcocystis suihominis, from pork. Humans may also serve intermediate hosts for non-human Sarcocystis spp. after the accidental ingestion of oocysts. This ingestion leads to muscular sarcocystosis.","Infectious disease"
"H00424","Defects in the degradation of sphingomyelin","Defects in the degradation of sphingomyelin is a group of autosomal recessive lysosomal storage diseases including Niemann-Pick disease (NPD), type A/B and Farber lipogranulomatosis. NPD caused by deficient acid sphingomyelinase (ASM) activity, and Farber lipogranulomatosis is caused by acid ceramidase deficiency, resulting in accumulation of sphingomyelin, ceramide and cholesterol in many organs. ASM and acid ceramidase are key enzymes of the two steps degradation of sphingomyelin and play important roles in normal membrane turnover.","Inherited metabolic disease; Lysosomal storage disease; Nervous system disease"
"H00616","Bowen-Conradi syndrome","Bowen-Conradi syndrome (BCS) is an autosomal-recessive disorder characterized by severely impaired prenatal and postnatal growth, profound psychomotor retardation. Most patients do not survive beyond the first year of life, as a result of complications associated with reduced mobility and failure to thrive. Recently, a missense mutation in EMG1 was reported to be the cause of BCS. EMG1 is a putative methyltransferase that is required for biogenesis of the 40S subunit of the ribosome.","Ribosomopathy"
"H02141","Autosomal dominant hypophosphatemic rickets","Autosomal dominant hypophosphatemic rickets (ADHR) is a rare genetic disorder, characterized by low serum phosphorus concentrations, rickets, osteomalacia, lower extremity deformities, short stature, bone pain and dental abscesses. The mutations in FGF23 cause ADHR. FGF23 is a circulatory hormone produced by osteocytes, but is also found in heart and liver. FGF23 helps maintain phosphorus homeostasis by inducing renal phosphate excretion.","Congenital disorder of metabolism"
"H00272","Multiple sulfatase deficiency","Multiple sulfatase deficiency (MSD) is a rare autosomal recessive lysosomal storage disorder caused by deficiency of sulfatase modifying factor 1 (SUMF1), which posttranslationally activates lysosomal sulfatases by generating formylglycine in their catalytic sites. MSD is known to combine sulfatase deficiency and clinical features of metachromatic leukodystrophy [DS:H00127]. The clinical course ranges from neonatal severe to mild juvenile cases.","Inherited metabolic disease; Nervous system disease; Lysosomal storage disease"
"H00040","Squamous cell carcinoma","Non-melanoma skin cancer, i.e. basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most frequent tumors and their number is still increasing world- wide. Approximately 200000 cases of SCC develop per year, causing about 2000 deaths. Unlike BCCs, which have no known precursor lesions, SCCs can emerge from actinic keratoses. As with BCC, risk for development of SCC is strongly influenced by the nature and dose of UV radiation and genetic backgrounds that regulate that interaction. Mutations in TP53 have been described in actinic keratoses, in situ SCC, and invasive SCC with UV signature lesions common, and a reported mutation rate as high as 45%. As with TP53, UV-induced mutations in HRAS and KRAS have also been characterized in both actinic keratoses and SCC. The reported frequency of RAS mutations in SCCs ranges from approximately 10% to almost 50%. Several recent studies have also reported mutations of p16 in up to 24% of SCCs. In addition to UV, a pathogenic role for human papillomavirus (HPV) in the development of SCC has also been proposed.","Cancer"
"H01192","Lysyl hydroxylase 3 deficiency","Lysyl hydroxylase 3 (LH3) deficiency is a connective tissue disorder, caused by defects in PLOD3 that encodes LH3. This disease is characterized by congenital malformations severely affecting many tissues and organs and revealing features of several collagen disorders. In addition to lysyl hydroxylase activity, LH3 has also collagen galactosyltransferase and glucosyltransferase activities. It has been reported that one mutation dramatically reduced the sugar-transfer activity of LH3.","Congenital malformation"
"H00286","Crohn disease","Crohn disease is a chronic, relapsing inflammatory bowel disease characterized by granulomatous inflammation, primarily localized to the terminal ileum. Most patients have involvement of the small intestine, but the other area of gastrointestinal tract may also be affected. In Western populations, over 50% of patients possess NOD2 mutations. Evidence exists that the NOD2 polymorphisms impair NF-kappaB activation and cytokine secretion in response to its ligand. The pathogenesis of Crohn's disease is also attributed to intestinal bacteria that may initiate mucosal inflammation in genetically susceptible individuals. Additional genes associated with the disease are recently being identified.","Immune system disease"
"H01354","Leigh syndrome","Leigh syndrome is a severe neurological disorder, characterized by bilaterally symmetrical necrotic lesions in the basal ganglia and brainstem. Most frequently the central nervous system is affected, with psychomotor retardation, seizures, nystagmus, optic atrophy, ataxia, or respiratory failure. Some patients also present with peripheral nervous system involvement or non-neurologic abnormalities. In the majority of cases, dysfunction of the mitochondrial respiratory chain complex or of the pyruvate dehydrogenase complex are responsible for the disease. Patterns of inheritance include X-linked recessive, autosomal recessive, and mitochondrial.","Inherited metabolic disease; Neurodegenerative disease; Mitochondrial disease"
"H01166","Sphingomonas paucimobilis infection","Sphingomonas paucimobilis is a yellow-pigmented, non-fermentative, gram-negative bacillus found in water. This bacterium has  been reported to cause nosocomial infections and is considered to originate from contaminated hospital environment and equipment.","Infectious disease"
"H00888","Nephrolithiasis/osteoporosis, hypophosphatemic","Nephrolithiasis/osteoporosis, hypophosphatemic is a genetically heterologous group of disorders characterized by the formation of renal calcium stones or bone demineralization due to impaired renal phosphate reabsorption. It is caused by either mutations in NPT2A, a sodium-phosphate cotransporter expressed in kidney and polarized osteoclasts, or in sodium-hydrogen exchanger regulatory factor (NHERF)1, that controls renal phosphate transport by trafficking NPT2A.","Urinary system disease; Musculoskeletal disease"
"H02387","Snijders Blok-Fisher syndrome","Snijders Blok-Fisher syndrome (SNIBFIS)  is a neurodevelopmental disorder with a broad phenotypic spectrum that includes intellectual disability and/or developmental delay, speech and language problems, hypotonia, and autism spectrum disorder. It has been reported that de novo mutations in POU3F3 cause this disease. POU3F3 is a well-known transcription factor involved in the development of the central nervous system.","Mental and behavioural disorder"
"H01502","Sjogren syndrome","Sjogren Syndrome (SS) is a chronic inflammatory systemic autoimmune disease characterized by lymphocytic infiltration of the exocrine glands leading to sicca symptoms of the eyes and mouth. Several systemic and extraglandular manifestations can develop, including fatigue, arthritis, and involvement of organs such as the skin, lungs, and kidneys. SS may occur as a primary disorder or in association with other systemic autoimmune diseases, traditionally defined as secondary SS, such as rheumatoid arthritis, and systemic lupus erythematosus. Salivary secretions from these patients exhibit elevated levels of antibodies and cytokines. This is accompanied by a reduction in oral phosphate levels and xerostomia due to reduced salivary flow, which can lead to infections, progressive caries, dysphagia and oral pain. Current tests for SS include sialometry, salivary scintigraphy, sialography, serological tests or minor salivary gland biopsies. Recently, salivary biomarkers of SS has been investigated. The etiology of SS is still unclear. Since there is a familial aggregation of primary SS, however, genetic factors have been suspected for a long time. Initially, HLA haplotypes were shown to be associated with primary SS. Recently, polymorphisms in the genes IRF5 and STAT4 have been convincingly identified and replicated in several studies as susceptibility factors.","Immune system disease; Skin and connective tissue disease"
"H01730","Myocardial infarction","Myocardial infarction (MI) or acute myocardial infarction (AMI) is a term for an event of heart attack. It is due to formation of plaques in the interior walls of the arteries resulting in reduced blood flow to the heart and injuring heart muscles because of lack of oxygen supply. The symptoms of MI include chest pain, which travels from left arm to neck, shortness of breath, nausea, epigastric discomfort, syncope, diaphoresis, and other factors. The diagnosis of MI is dependent on the sensitivity and specificity of the clinical criteria, electrocardiographic (ECG) findings, imaging studies and biomarkers used to detect death of cardiomyocytes. The treatment of MI includes, aspirin tablets, and to dissolve arterial blockage injection of thrombolytic or clot dissolving drugs such as tissue plasminogen activator, streptokinase or urokinase in blood within 3 h of the onset of a heart attack. Nitroglycerin and antihypertensive drugs such as beta-blockers and ACE inhibitors may also be used to lower blood pressure and to improve the oxygen demand of heart.","Cardiovascular disease"
"H01962","Congenital muscular dystrophy type 1D","Congenital muscular dystrophy type 1D (MDC1D) is a form of congenital muscular dystrophy with severe mental retardation and abnormal glycosylation of alpha-dystroglycan. MDC1D is caused by mutations in LARGE gene.","Nervous system disease; Musculoskeletal disease; Congenital disorder of metabolism"
"H01708","Diffuse idiopathic skeletal hyperostosis","Diffuse idiopathic skeletal hyperostosis (DISH), also known as Forestier disease, is a systemic noninflammatory disease characterized by ossification of the entheses. It affects mainly elderly men, and involves the ossification of the anterior longitudinal ligament (OALL). Although it is asymptomatic in some occasions, the disease may produce dysphagia, dysphonia, and exceptionally breathing difficulties due to airway compromise. In these cases, early surgery is recommended to alleviate airway obstruction. Although the hallmark of the DISH is considered to be the anterolateral aspect of the thoracic spine, various signs and symptoms is not limited to the spine and has often been reported to involve multiple peripheral locations as well. While the cause of DISH remains unclear, mechanical factors, genetic factors, environmental factors, drugs, and metabolic conditions have been hypothesized to be relevant. Most of the current theories focus on the pathologic OALL. There's no cure for DISH. Therapy for DISH is based on symptomatic and empiric treatment. In general, physical therapy, analgesics, antiinflammatory drugs, and muscle relaxants have been successful in managing the majority of patients with DISH.","Musculoskeletal disease"
"H02179","Rippling muscle disease","Rippling muscle disease (RMD) is an autosomal-dominant disorder of skeletal muscle characterized by signs of increased muscle irritability, such as percussion-induced rapid contraction (PIRC), percussion-induced muscle mounding (PIMM), and/or electrically silent muscle contractions (rippling muscle). Many cases of RMD are caused by mutations in caveolin-3, and aberrations in the tubular system are commonly observed.","Nervous system disease; Musculoskeletal disease"
"H01398","Primary hyperammonemic disorders (Urea cycle disorders)","Hyperammonemia is a metabolic condition characterized by elevated levels of ammonia in the blood, and may result in irreversible brain damage if not treated early and thoroughly. Hyperammonemia can be classified into primary or secondary hyperammonemias depending on the underlying pathophysiology. Detoxification of ammonia is mainly accomplished by the urea cycle in periportal hepatocytes. If the urea cycle is directly affected by a defect of any of the involved enzymes or transporters, this results in primary hyperammonemia.","Inherited metabolic disease"
"H00078","Frontotemporal lobar degeneration","Frontotemporal lobar degeneration (FTLD) is a heterogeneous syndrome with the common feature being a relatively selective degeneration of the frontal and temporal lobes. Multiple genes have been implicated in FTLD including microtubule associate protein tau (MAPT), progranulin (PGRN),Valosin-containing protein (VCP) and chromatin modifying protein 2B (CHMP2B). MAPT mutations are associated with tau pathology. Mutations in progranulin and valosin are associated with TDP-43 inclusions. The CHMP2B mutations are associated with ubiquitin-positive pathology.","Neurodegenerative disease"
"H00844","Familial benign chronic pemphigus","Familial benign chronic pemphigus, also known as Hailey-Hailey disease, is a rare, autosomal dominant skin disorder. The clinical features are uncomfortable skin blisters and vegetative lesions caused by friction. Lesions generally begin between 20 and 40 years of age. In two third of all cases, positive family history is detected. Mutations in ATP2C1 that encodes a secretory pathway Ca2+/Mn2+-ATPase in the Golgi apparatus impair desmosomal keratinocyte adhesion in Hailey-Hailey disease.","Congenital malformation"
"H01996","Pyruvate dehydrogenase phosphatase deficiency","Pyruvate dehydrogenase phosphatase (PDP) deficiency has previously been confirmed only in a few cases. PDP is an enzyme which regulates the activity of the pyruvate dehydrogenase complex. It has been reported that the mutations in PDP1 gene result in lactic acidemia, progressive neurodegeneration, and seizure activity, culminating in early death.","Inherited metabolic disease; Neurodegenerative disease"
"H01737","Epidermolysis bullosa","Inherited epidermolysis bullosa (EB) is a diverse group of disorders that encompass dozens of clinically and genotypically distinct diseases. It is characterized by mechanically fragile skin that readily blister. Most of the more severe subtypes are associated with clinically significant extracutaneous complications. Some subtypes may lead to death, even in early infancy. There are four major types of EB: EB simplex, junctional EB, dystrophic EB, and Kindler syndrome.","Congenital malformation"
"H02380","D-glyceric aciduria","D-glyceric aciduria is a rare inborn error of serine and fructose metabolism. Most affected individuals have presented with neurological symptoms. It has been reported that mutations in GLYCTK gene encoding D-glycerate kinase cause this disease.","Congenital disorder of metabolism"
"H01505","Inclusion body myositis","Inclusion body myositis (IBM) is the most frequent acquired myopathy after age 45. It is distinguished from other inflammatory myopathies by its selective pattern of muscle involvement and slowly progressive course, and by the combination of inflammatory and degenerative muscle pathology and multi-protein deposits in muscle tissue. It typically presents with chronic insidious proximal leg and/or distal arm asymmetric muscle weakness leading to recurrent falls and loss of dexterity. Creatine kinase (CK) is elevated in IBM and needle electromyography (EMG) mostly shows a chronic irritative myopathy. Muscle histopathology demonstrates endomysial inflammatory exudates surrounding and invading non-necrotic muscle fibers often times accompanied by rimmed vacuoles and protein deposits. IBM is refractory to all known immunosuppressive therapies. It has been shown in small short-term trials that individualised exercise programs can lead to improvement or maintenance of muscle strength and aerobic capacity.","Nervous system disease; Musculoskeletal disease"
"H01161","Aromatic L-amino acid decarboxylase deficiency","Aromatic L-amino acid decarboxylase (AADC) deficiency is an autosomal recessive disorders of monoamine neurotransmitter metabolism, clinically characterized by vegetative symptoms, oculogyric crises, dystonia, and severe neurologic dysfunction in infancy. Mutations in the gene encoding for the enzyme AADC (DDC) lead to a severe combined deficiency of serotonin and the two catecholamines dopamine and norepinephrine.","Nervous system disease"
"H00281","GM1 gangliosidosis","GM1-gangliosidosis is an autosomal recessive lysosomal storage disorder caused by deficient beta-galactosidase activity. The enzymatic defect results in the accumulation of GM1 ganglioside in nervous tissues and a highly variable storage of keratan sulfate and glycopeptides in visceral and skeletal tissues. There are three main clinical variants, infantile (type I), juvenile (type II), and adult (type III), categorized by severity of symptoms and variable residual enzymatic activity of beta-galactosidase.","Inherited metabolic disease; Lysosomal storage disease; Nervous system disease"
"H01353","Chromobacterium violaceum infection","Chromobacterium violaceum is a gram-negative, facultative anaerobic, opportunistic pathogenic bacterium that infects both humans and animals. The major symptoms in most of the cases with fatal results seem to be sepsis, multiple liver abscesses, and diffuse pustular dermatitis. Some studies have reported instances of untreated C. violaceum causing brain abscess and diarrhea. Recent findings indicate that the type III secretion system (T3SS) encoded by Chromobacterium pathogenicity islands 1 and 1a (Cpi-1/-1a) is critical for C. violaceum pathogenesis.","Infectious disease"
"H00047","Gallbladder cancer","Gallbladder cancer (GBC) is a relatively uncommon neoplasm, however its prognosis is poor with less than a 5% 5-year survival rate. There are considerable geographic differences in its incidence and etiology. Two main pathways of GBC pathogenesis have been identified. The most common is associated with gallstones and chronic inflammation of the gallbladder, whereas a second, less frequent pathway is associated with a congenital abnormality of the pancreatic bile-duct junction, which is particularly common in Japan. TP53 inactivation has an important and early role in GBC associated with gallstones and chronic inflammation. Although KRAS mutations are rarely detected in GBC associated with gallstones, they are frequent and early events in tumors associated with congenital abnormality of the pancreatic bile-duct junction.","Cancer"
"H01195","VACTERL/VATER association","The acronym VATER/VACTERL association refers to the rare, non-random co-occurrence of vertebral defects (V), anorectal malformations (A), cardiac defects (C), tracheo-esophageal fistula with or without esophageal atresia (TE), renal malformations (R), and limb defects (L). It is typically defined by the presence of at least three of these cardinal features. The aetiology has been identified only in a small fraction of patients to date, likely due to factors such as a high degree of clinical and causal heterogeneity, the largely sporadic nature of the disorder, and the presence of many similar conditions. Chromosomal abnormalities have been described in rare individual cases and proposed as possible causal factors, including: deletions of distal 13q, ring chromosome 12, and 6q; duplication on 9q; mutations in PTEN, HOXD13, and ZIC3; and a mitochondrial substitution.","Congenital malformation"
"H00275","Cystinosis","Cystinosis is an autosomal recessive lysosomal storage disorder caused by deficiency of lysosomal cystine transporter, which leads to intracellular cystine crystals, widespread cellular destruction, renal Fanconi syndrome in infancy, renal glomerular failure in later childhood, and other systemic complications. Since the introduction of cysteamine into the pharmacological management of cystinosis, well-treated adolescent and young adult patients have experienced normal growth and maintenance of renal glomerular function.","Inherited metabolic disease; Lysosomal storage disease"
"H00611","Popliteal pterygium syndrome (PPS)","Popliteal pterygium syndrome (PPS) is an autosomal dominant orofacial cleft syndrome caused by IRF6 mutations. Clinical manifestations of PPS include cleft lip and/or palate in association with webcausing popliteal connective tissue, syndactyly, and genital abnormalities.","Congenital malformation"
"H02146","Glass syndrome","Glass syndrome, also known as SATB2-associated syndrome (SAS), is a recently described syndrome characterized by developmental delay/intellectual disability with absent or limited speech development, craniofacial abnormalities including palatal and dental abnormalities, behavioral problems, and dysmorphic features. Alterations to the SATB2 gene can result from a variety of different mechanisms that include contiguous deletions, intragenic deletions and duplications, translocations with secondary gene disruption, and point mutations.","Chromosomal abnormality"
"H02374","Blastocystosis","Blastocystosis is an infectious disease caused by Blastocystis sp., an anaerobic intestinal parasite of humans and a wide range of animals. Blastocystis sp. is the only stramenopiles known to cause infection in humans. It is possible to recognize the fecal-oral transmission, through ingestion of contaminated food and water, and zoonotic spreads.","Infectious disease"
"H00423","Sphingolipidosis","The sphingolipidoses are a group of monogenic inherited diseases caused by defects in the system of lysosomal sphingolipid degradation, with subsequent accumulation of non-degradable storage material in one or more organs.","Congenital disorder of metabolism"
"H02389","Familial dyskinesia with facial myokymia","Familial dyskinesia with facial myokymia (FDFM) is an autosomal dominant disorder characterized by paroxysmal chorea, dystonia, and facial myokymia. Missense mutations in ADCY5 were reported as the cause of FDFM. ADCY5 is one of membrane-bound adenylyl cyclases. ADCY5 expression is particularly high in striatum and myocardium.","Nervous system disease"
"H00288","Familial Mediterranean fever","Familial Mediterranean fever (FMF) is the most prevalent hereditary periodic fever, affecting 0.1% in people of Mediterranean descent. It is also reported throughout the world's populations. FMF is an autosomal recessive disorder caused by missense mutations in the MEFV gene, which encodes the pyrin protein. Mutations in pyrin may lead to uncontrolled inflammation due to IL-1beta hyperactivation. FMF is characterized by recurrent inflammatory fevers with sterile peritonitis, pleuritis, arthritis, myalgia and erysipelas-like skin lesions. Renal amyloidosis is the most severe complication, leads to renal failure. These symptoms start before 20 years of age in about 90% of cases.","Immune system disease"
"H01168","Sea-blue histiocyte disease","Sea-blue histiocyte disease is a clinical entity characterized by splenomegaly, mild purpura secondary to thrombocytopenia, and most often with a relatively prolonged benign course. Numerous sea-blue histiocytes are observed in many organs including the bone marrow, liver, and spleen. This disorder is classified as either primary or secondary; most cases are secondary to lipid metabolic diseases. A mutation in the APOE gene has been reported.","Inherited metabolic disease"
"H01954","Glycogen storage disease type XIV","Glycogen storage disease type XIV(GSD-XIV), also known as congenital disorder of glycosylation type It, is an autosomal recessive disorder of glycogen metabolism. GSD-XIV is caused by mutations in the PGM1 gene, which encodes the phosphoglucomutase. The clinical manifestations include hepatopathy, bifid uvula, malignant hyperthermia, hypogonadotropic hypogonadism, growth retardation, hypoglycemia, myopathy, dilated cardiomyopathy, and cardiac arrest.","Inherited metabolic disease"
"H00886","Donnai-Barrow syndrome","Donnai-Barrow syndrome is a rare autosomal recessive disorder of multiple anomalies resulting from mutations in the LRP2 gene. It is characterized by agenesis of the corpus callosum, typical craniofacial features (ocular hypertelorism, enlarged fontanelle), ophthalmological abnormalities (high myopia, iris stromal hypoplasia), severe sensorineural deafness, congenital diaphragmatic hernia, and proteinuria. The diagnosis is confirmed by detection of mutations in LRP2.","Congenital malformation"
"H00872","Trismus-pseudocamptodactyly syndrome","Trismus-pseudocamptodactyly syndrome is a rare autosomal dominant distal arthrogryposis characterized by the inability to open the mouth (trismus) causing difficulty with mastication, and an unusual camptodactyly of the fingers that is apparent only while attempting dorsiflexion of the wrist (pseudocamptodactyly).","Congenital malformation"
"H00618","Amelogenesis imperfecta hypoplastic-hypomaturation with taurodontism","Amelogenesis imperfecta hypoplastic-hypomaturation with taurodontism (AIHHT) is a condition characterized by enamel defects and enlarged pulp chambers. Unlike its allelic disorder trichodentoosseous dysplasia, AIHHT patients do not show hair and bone abnormalities. AIHHT is an autosomal dominant trait.","Mouth and dental disease"
"H01157","Agrobacterium radiobacter infection","Agrobacteria are small, gram-negative bacilli widely distributed in soil. They are best known for the phytopathogenicity, causing tumorigenic disease in plants. However, Agrobacterium spp. are also recognized as rare human pathogens affecting mostly immunocompromised or chronically debilitated hosts and patients with indwelling catheters. Clinical manifestations include bacteremia, peritonitis, and deltoid muscle myositis.","Infectious disease"
"H00085","Agammaglobulinemias","There are three major categories of antibody deficiencies: (a) defects in early B cell development, (b) hyper-IgM syndromes (also called class switch recombination defects), and (c) common variable immunodeficiency (CVID). Category (a) consists of agammaglobulinaemias. Defects in early B cell development are characterized by the onset of recurrent bacterial infections in the first 5 years of life, profound hypogammaglobulinemia, markedly reduced or absent B cells in the peripheral circulation, and (in the bone marrow) a severe block in B cell differentiation before the production of surface immunoglobulin-positive B cells. Mutations in Btk, the gene responsible for X-linked agammaglobulinemia (XLA), account for approximately 85% of affected patients. Approximately half of the remaining patients have mutations in genes encoding components of the pre-B cell receptor (pre-BCR) or BCR, including mu heavy chain (IGHM); the signal transduction molecules Ig-alpha (CD79A) and Ig-beta (CD79B); and lambda 5 (IGLL1), which forms the surrogate light chain with Vpre-B. A small number of patients with defects in BLNK, a scaffold protein that assembles signal transduction molecules activated by cross-linking of the BCR, have been reported.","Primary immunodeficiency"
"H01365","Leber hereditary optic neuropathy and dystonia","Leber hereditary optic neuropathy and dystonia (LDYT) is a maternally-inherited mitochondrial disorder characterized by variable combinations of visual loss and progressive generalized dystonia. LDYT is a unique oxidative phosphorylation disorder caused by mutations in mitochondrial DNA.","Nervous system disease; Congenital disorder of metabolism"
"H02184","Metatropic dysplasia","Metatropic dysplasia is an autosomal dominant skeletal dysplasia characterized by short extremities, a short trunk with progressive kyphoscoliosis, and craniofacial abnormalities that include a prominent forehead, midface hypoplasia, and a squared-off jaw. Mutations in the gene encoding TRPV4, a calcium permeable ion channel, have recently been identified in nonlethal metatropic dysplasia.","Congenital malformation"
"H01701","Pituitary TSH hypersecretion","Pituitary TSH hypersecretion is disease of the anterior portion of the pituitary resulting in hypersecretion of thyroid stimulating hormone (TSH). It includes two forms of central hyperthyroidism, i.e. TSH-secreting pituitary adenoma (TSHoma) and resistance to thyroid hormone action (RTH). The incidence of hyperthyroidism due to a TSHoma is extremely low, 1-2% of all cases of hyperthyroidism. Most of the tumors are macroadenomas usually presenting with symptoms such as headache and/or visual field impairment while the symptoms of hyperthyroidism seem to be milder compared with those caused by primary hyperthyroidism. First-line treatment of TSHoma is pituitary adenomectomy followed by irradiation in the case of surgical failure. However, medical treatment with somatostatin analogs, such as octreotide and lanreotide, are effective in reducing TSH secretion.","Endocrine disease"
"H01533","Japanese encephalitis","Japanese encephalitis is an infection of the central nervous system caused by Japanese encephalitis virus (JEV), a flavivirus in the Flaviviridae family of +ssRNA viruses, and transmitted by Culex mosquitoes. JEV was first isolated in 1924 in Japan.","Infectious disease"
"H02170","Microphthalmia, syndromic","Microphthalmia can be defined as a reduced size of the globe in the orbit. More than 50% of individuals with microphthalmia have extraocular findings, most commonly involving the limbs, musculoskeletal system and the craniofacial region with anomalies of the face, ear and neck.","Congenital malformation"
"H00627","Premature ovarian failure","Premature ovarian failure (POF) is characterized by amenorrhea before the age of 40 years with elevated levels of gonadotrophin (LH and FSH) and low levels of gonadal hormones (estrogens and inhibins). The causes of POF can be categorized into genetic and environmental mechanisms. X chromosome defects such as Turner syndrome or trisomy X as well as many genes including BMP15 andFMR1 are associated with POF development. For the environmental causes, medical intervention including surgeries and chemotherapies may lead to POF. Autoimmune ovarian failure consists another large category of POF.","Reproductive system disease"
"H00415","Hepatitis E","Hepatitis E is an infectious disease caused by hepatitis E virus (HEV) belonging to the Hepeviridae family of +ssRNA viruses. HEV is transmitted through the fecal-oral route.","Infectious disease"
"H02342","Frontotemporal dementia and amyotrophic lateral sclerosis","Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are genetically heterogeneous disorders. Mutations in the several genes and a repeat expansion in the C9orf72 gene have been reported to be associated with both diseases (FTDALS). Genes linked to both diseases may converge into a common pathogenetic pathway, explaining the overlap of clinical symptoms.","Nervous system disease"
"H00071","Hereditary fructose intolerance","Hereditary fructose intolerance or fructosemia (fructose in the blood) is an autosomal recessive disorder caused by a defect in an aldolase gene (aldolase B), which is normally expressed in liver and kidney. Aldolase is the enzyme that converts fructose 6P (a six-carbon compound) to glycerone-P and glyceraldehyde-3P (two three-carbon compounds).","Inherited metabolic disease"
"H01391","Familial episodic pain syndrome","Familial episodic pain syndrome (FEPS) is an autosomal dominant neurological disorder characterized by episodes of debilitating pain in the upper body and the distal lower extremities, triggered by conditions of fatigue, fasting, and cold. Gain-of-function mutations in TRPA1, SCN10A, and SCN11A can be causative of FEPS.","Musculoskeletal disease"
"H00243","Hyperkalemic distal renal tubular acidosis (RTA type 4)","Renal tubular acidosis (RTA) is characterized by metabolic acidosis, a severe disturbance of extracellular pH homeostasis, due to renal impaired acid excretion. Type 4 RTA is a heterogeneous group of disorders associated with hyperkalemia due to aldosterone deficiency or impairment in aldosterone molecular signaling. Primary pseudohypoaldosteronism type 1 (PHA1) is characterized by salt-wasting, hyperkalemia, and metabolic acidosis in the presence of markedly elevated plasma renin activity and aldosterone concentration. In the autosomal dominant form, aldosterone resistance is due to heterozygous mutations in the mineralocorticoid receptor gene. In the autosomal recessive form, aldosterone resistance is caused by loss-of-function homozygous mutations in the genes encoding one of the three constitutive subunits (alpha, beta, and gamma) of the epithelial Na+ channel (SCNN1A, SCNN1B, and SCNN1G). Other inherited cause of type 4 RTA includes hyperkalaemia associated with hypertension and low or normal levels of plasma aldosterone. This syndrome is called pseudohypoaldosteronism type 2 (PHA2), or Gordon's syndrome, which results in a renal aldosterone resistance. Mutations in the genes encoding WNK1 and WNK4 kinases (WNK1 and WNK4), which regulate ion-transportors on renal tubules, were identified in patients with PHA2. Acquired hyperkalemic RTA is observed in the context of mineralocorticoid deficiency, systemic lupus erythematosus, and AIDS nephropathy. It is also often seen in a number of tubulointerstitial renal diseases. Finally, a great number of drugs may induce hyperkalemic RTA.","Urinary system disease"
"H02148","Low molecular weight proteinuria with hypercalciuria and nephrocalcinosis","Low molecular weight proteinuria with hypercalciuria and nephrocalcinosis is a form of X-linked hypercalciuric nephrolithiasis. It is renal proximal tubulopathy in Japanese children that has similarities to Dent disease. However, patients do not suffer from rickets or renal failure. Mutations of a renal chloride channel gene, CLCN5, have been reported.","Urinary system disease"
"H00049","Myxoid liposarcoma","Liposarcoma(LS) represents the most common soft-tissue sarcoma of adults and occurs most often in the thigh and retroperitoneum. LSs are subclassified into well-differentiated, myxoid, round cell, and pleomorphic types. The myxoid type, the most common subtype, accounts for approximately 40% to 54% of all liposarcomas. The karyotypic hallmark of myxoid LS is the t(12;16)(q13;p11), present cytogenetically in >90% of the cases. The translocation leads to the fusion of the DDIT3(CHOP) and FUS(TLS) genes at 12q13 and 16p11, respectively, and the generation of a FUS-DDIT3 hybrid protein. In 4 cases of myxoid LS, a variant chromosomal translocation has been described, t(12;22), in which DDIT3 fuses instead with EWSR1(EWS), a gene highly related to TLS.","Cancer"
"H00875","Megaloencephalic leukoencephalopathy with subcortical cysts","Megaloencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare leukodystrophy characterized by macrocephaly and a slowly progressive clinical course marked by spasticity and cognitive decline. Magnetic resonance imaging (MRI) shows bilateral extensive white-matter changes with cysts in the temporal regions. Based on the clinical and MRI features, MLC can be distinguished from other conditions (ie, Alexander disease [DS:H00065], Canavan disease [DS:H00074], glutaric acidemia type I [DS:H00178]) that present in infancy with megalencephaly. An autosomal recessive mutations in the MLC1 gene have been shown to cause this condition. Recently, mutations in HEPACAM gene are reported to be associated with MLC.","Nervous system disease; Congenital disorder of metabolism"
"H01953","Glycogen storage disease type XIII","Glycogen storage disease type XIII (GSD-XIII) is an autosomal recessive disorder of glycogen metabolism. GSD-XIII is caused by mutations in the ENO3 gene, which encodes the muscle beta-enolase. The typical presentation is exercise intolerance and myalgias.","Inherited metabolic disease"
"H00881","Li-Fraumeni syndrome","Li-Fraumeni syndrome (LFS) is a familial clustering of early onset tumors including sarcomas, breast cancers, brain tumors and adrenocortical carcinomas (ADR). Initially considered as a rare syndrome, LFS and its variants are increasingly recognized as one of the most frequent and diverse forms of predisposition to cancer. Most cases identified and characterized to date are associated with dominantly inherited germ line mutations in the tumor suppressor gene TP53 (p53). In a subset of non-p53 patients with LFS, CHEK2 has been identified as another predisposing locus. LFS is diagnosed on the basis of the confirmed clinical diagnostic criteria.","Other disease"
"H01739","Polycystic ovary syndrome","Polycystic ovary syndrome (PCOS) is a common heterogeneous endocrine disorder characterized by elevated androgen levels, menstrual irregularities, and/or small cysts on one or both ovaries. Clinical manifestations include oligomenorrhea or amenorrhea, hirsutism, and frequently infertility. Clinical signs of PCOS include elevated luteinizing hormone (LH) and gonadotropin-releasing hormone (GnRH) levels, whereas follicle-stimulating hormone (FSH) levels are muted or unchanged. As a result of the increase in GnRH, stimulation of the ovarian theca cells, in turn, produces more androgens. Risk factors for PCOS in adults includes insulin resistance (IR), type 2 diabetes, obesity, and cardiovascular disease. PCOS can be described as an oligogenic disorder in which the interaction of a number of genetic and environmental factors determine the heterogeneous, clinical, and biochemical phenotype. Management of clinical manifestations of PCOS includes oral contraceptives for menstrual irregularities and hirsutism. Treatment options for infertility include clomiphene, laparoscopic ovarian drilling, gonadotropins, and assisted reproductive technology.","Endocrine system disease; Reproductive system disease"
"H01396","Moyamoya disease","Moyamoya disease is a rare cerebrovascular disease characterized by a progressive stenosis or occlusion of the terminal portion of the internal carotid artery. This disease is associated with the compensatory development of abnormally thin and fragile collateral vessels at the base of the brain.","Cardiovascular disease"
"H00244","Pseudohypoparathyroidism","Pseudohypoparathyroidism refers to a heterogeneous group of autosomal dominant disorders characterized by hypocalcemia and hyperphosphatemia due to resistance to parathyroid hormone. The disease phenotype of type Ia is characterized by Albright hereditary osteodystrophy (AHO) and resistance PTH and many other hormones, while that of type Ib shows hypothyroidism due to resistance to TSH restricted to renal tubule cells.","Endocrine and metabolic disease"
"H00076","Cockayne syndrome","Cockayne syndrome (CS) is a rare recessive disorder characterized by progressive multisystem abnormalities such as postnatal growth deficiency, progressive pigmentary retinopathy, sensorineural hearing loss, dental caries and neurological degeneration. CS has thus been classified as a segmental premature-aging syndrome. CSA caused by mutation in the gene encoding the group 8 excision-repair cross-complementing protein (ERCC8) is early childhood onset in the second year of life, CSB caused by mutation in the ERCC6 gene is late childhood onset with mild symptoms. ERCC8 encodes a Walker domain (WD)-repeat protein involved in the transcription-coupled repair system of the actively transcribed DNA. ERCC6 protein is at the interface of transcription and DNA repair and is involved in transcription-coupled and global genome-DNA repair, as well as in general transcription.","Neurodegenerative disease"
"H01998","Pyruvate dehydrogenase E1-beta deficiency","Defects in the pyruvate dehydrogenase (PDH) complex are an important cause of primary lactic acidosis. Recently, patients with PDH deficiency attributable to mutations in PDHB (E1 beta subunit) has been reported. Primary defects in the E1 beta subunit of the PDH complex appear to be extremely rare.","Inherited metabolic disease"
"H00412","Hepatitis B","Hepatitis B is an infectious disease caused by hepatitis B virus (HBV) belonging to the Hepadnaviridae family of dsDNA-RT viruses. Both acute and chronic hepatitis B can be caused by blood-borne HBV infections. The risk of developing chronic hepatitis B is directly related to the age of first infection, much higher for infants. Chronic hepatitis B may eventaully lead to cirrhosis and hepatocellular carcinoma.","Infectious disease"
"H02345","Autosomal recessive peripheral neuropathy (PNRIID)","Autosomal recessive peripheral neuropathy with or without impaired intellectual development (PNRIID) is characterized by sensorymotor polyneuropathy and distal muscle weakness. It could be associated with mild intellectual disability, strabismus, and ophthalmoparesis. It has been reported that PNRIID is caused by mutations in the MCM3AP, encoding the germinal center associated nuclear protein (GANP).","Nervous system disease"
"H02177","Androgen insensitivity syndrome","Androgen insensitivity syndrome (AIS) is typically characterized by evidence of feminization of the external genitalia at birth, abnormal secondary sexual development in puberty, and infertility in individuals with a 46,XY karyotype. AIS represents a spectrum of defects in androgen action. Pathogenesis is the result of mutations in the X-linked androgen receptor (AR) gene, which encodes for the ligand-activated androgen receptor.","Endocrine and metabolic disease"
"H00620","Axenfeld-Rieger syndrome","Axenfeld-Rieger syndrome (RIEG) is a rare autosomal dominant disorder mainly affecting the anterior segment of the eyes congenitally. The ocular features include malformations of aniridia, coloboma of the iris, and ectopic pupils. Open-angle glaucoma can lead to blindness and is the main target of treatment in RIEG. Defects in other organ systems, typically the craniofacial, dental, and umbilical abnormalities, are also part of the disorder.","Congenital malformation"
"H01534","Western equine encephalitis","Western equine encephalitis is an infection of the central nervous system caused by Western equine encephalitis virus (WEEV), an alphavirus in the Togaviridae family of +ssRNA viruses, and transmitted by Culex mosquitoes. WEEV was first isolated in 1930 in California, USA.","Infectious disease"
"H02183","Parastremmatic dwarfism","Parastremmatic dwarfism is a rare disorder, caused by TRPV4 mutations. Clinical symptoms include shortening of the trunk because of platyspondyly and scoliosis, as well as flexum deformity in both knees. The term 'parastremmatic' is used from the Greek parastremma (distorted limb).","Congenital malformation"
"H01706","Delayed endolymphatic hydrops","Delayed endolymphatic hydrops (DEH) is a disorder, characterized by episodic vertigo that develops some time after the onset of a profound, typically unilateral sensorineural hearing loss. DEH can be differentiated from Meniere's disease. The age of onset of symptoms is typically in later childhood and adolescence or between 40 and 60 years of age. DEH probably is caused by atrophy or fibrous obliteration of the endolymphatic resorptive system of the membranous labyrinth. It has been reported that genetic factors may sometimes be the cause of this disease. Two types of DEH exist: the ipsilateral type, in which the ear with profound hearing loss suffers progressive endolymphatic hydrops, and the contralateral type, in which the formation of progressive endolymphatic hydrops takes place in the ear opposite to the previously deafened ear. DEH requires conservative treatment, such as that typically used for Meniere's disease, including the appropriate concomitant use of diuretics, such as isosorbide or steroids for at least 3-6 months. When recurrent episodic vertigo cannot be remedied through conservative treatment, labyrinthectomy and vestibular neurectomy on the deaf ear are curative for ipsilateral DEH. However, no such surgical treatment is available for the contralateral type.","Nervous system disease"
"H01362","Dermatitis herpetiformis","Dermatitis herpetiformis (DH) is a chronic, polymorphic, pruritic skin disease that develops mostly in patients with latent gluten-sensitive enteropathy. There is an association with the genotypes HLA DR3, HLA DQw2, found in 80-90% of cases. Owing to the granular immunoglobulin (Ig) A deposition at the tips of the papillary dermis and to the subepidermal blister formation associated with neutrophilic accumulations underlying the basement membrane, DH is considered to be an autoimmune blistering disease.","Immune system disease"
"H01150","Phenylobacterium infection","Phenylobacterium is a gram-negative rod bacterium. The first case of cutaneous infectious granuloma caused by this bacterium was reported in 2010.","Infectious disease"
"H00082","Graves disease","Graves disease is a common form of chronic autoimmune thyroid disease (AITD), and is characterized by overstimulation of the thyroid gland with agonistic anti-thyrotropin (TSH) receptor autoantibodies. This overstimulation leads to follicular hypertrophy and hyperplasia, causing thyroid enlargement, as well as increases in thyroid hormone production and the fraction of triiodothyronine (T3) relative to thyroxine (T4) in thyroid secretion. Thyroid autoimmune diseases are regarded as polygenic disorders resulting from the combination of a genetic predisposition in conjunction with an environmental trigger. Two main approaches have been employed to locate susceptibility loci for AITD, namely case control candidate gene studies and genome-wide linkage screens. Case control candidate gene studies have been employed to investigate numerous genes for association with AITD, but to date, only the human leucocyte region (HLA) on chromosome 6p21 and the cytotoxic T lymphocyte associated 4 (CTLA-4) gene on chromosome 2q33 have been consistently shown to be associated with disease.","Immune system disease"
"H00022","Bladder cancer","The urothelium covers the luminal surface of almost the entire urinary tract, extending from the renal pelvis, through the ureter and bladder, to the proximal urethra. The majority of urothelial carcinoma are bladder carcinomas, and urothelial carcinomas of the renal pelvis and ureter account for only approximately 7% of the total. Urothelial tumours arise and evolve through divergent phenotypic pathways. Some tumours progress from urothelial hyperplasia to low-grade non-invasive superficial papillary tumours. More aggressive variants arise either from flat, high-grade carcinoma in situ (CIS) and progress to invasive tumours, or they arise de novo as invasive tumours. Low-grade papillary tumors frequently show a constitutive activation of the receptor tyrosine kinase-Ras pathway, exhibiting activating mutations in the HRAS and fibroblast growth factor receptor 3 (FGFR3) genes. In contrast, CIS and invasive tumors frequently show alterations in the TP53 and RB genes and pathways. Invasion and metastases are promoted by several factors that alter the tumour microenvironment, including the aberrant expression of E-cadherins (E-cad), matrix metalloproteinases (MMPs), angiogenic factors such as vascular endothelial growth factor (VEGF).","Cancer"
"H00210","Wilson disease","Wilson disease is an autosomal recessive disorder caused by mutation of a P-type ATPase important for copper excretion into bile, leading to copper accumulation in the liver. Toxic concentration of copper affects brain and kidney as well as liver.","Inherited metabolic disease; Nervous system disease; Liver disease"
"H00674","Anemia due to disorders of nucleotide metabolism","Abnormalities in erythrocyte nucleotide metabolism are associated with hereditary nonspherocytic hemolytic anemia. Deficiency of adenylate kinase and pyrimidine 5'-nucleotidase shorten the red cell lifespan.","Hematologic disease"
"H02123","Celiac disease","Celiac disease is a chronic gluten intolerance that occurs in genetically predisposed individuals. The ingestion of gluten causes chronic inflammation of the small intestinal mucosa, leading to nutrient malabsorption. Susceptibility to celiac disease is strongly associated with particular HLA class II alleles. However, non-HLA genetic factors are likely to be required for the development of the disease. It has been reported that CTLA4 and MYO9B gene polymorphisms are associated with predisposition to celiac disease.","Digestive system disease"
"H02311","Molybdenum cofactor deficiency","Molybdenum cofactor deficiency (MOCOD) is a rare  autosomal recessive disorder that leads to early childhood death. Mutations have been identified in three genes: MOCS1, MOCS2, and GEPH. These mutations result in the simultaneous loss of all MoCo-dependent enzyme activities, that include sulfite oxidase, xanthine dehydrogenase, and aldehyde oxidase. MOCOD results in neonatal seizures and other neurological symptoms identical to those of sulphite oxidase deficiency [DS:H01237].","Congenital disorder of metabolism"
"H00446","Craniofacial-deafness-hand syndrome","Craniofacial-deafness-hand syndrome is inherited as an autosomal dominant or X-linked mutation characterized by a flat facial profile, hypoplastic nose, and a sensorineural hearing loss. A missense mutation in the PAX3 has been detected in patients with the disease.","Other congenital malformation"
"H01594","Myasthenia gravis","Myasthenia gravis (MG) is an autoimmune disorder characterized by a defective transmission of nerve impulses to muscles leading to muscle weakness and fatigability. Some, but not all, muscles are affected and not necessarily symmetrically. Increased weakness with continued muscle activity represents a diagnostic clue for MG, but these clinical features can vary. MG is B-cell mediated, and is associated with antibodies directed against the acetylcholine receptor (AChR), muscle-specific kinase (MUSK), lipoprotein-related protein 4 (LRP4), or agrin in the postsynaptic membrane at the neuromuscular junction. Patients should be classified into subgroups to help with therapeutic decisions and prognosis. Subgroups based on serum antibodies and clinical features include early-onset, late-onset, thymoma, MUSK, LRP4, antibody-negative, and ocular forms of myasthenia gravis. Agrin-associated MG might emerge as a new entity. The prognosis is good with optimum symptomatic, immunosuppressive, and supportive treatment. The evolution of MG is unpredictable, but it is generally characterized by the occurrence of relapses, sometimes subsequent to remissions and a worsening trend. For 85% of MG patients, the maximum severity is reached within less than 3 years.","Immune system disease; Nervous system disease"
"H00680","Primary failure of tooth eruption","Primary failure of tooth eruption (PFE) is a condition in which tooth retention occurs without mechanical interference. Defects in PTHR1 are the cause of PFE.","Mouth and dental disease"
"H01752","ATR-X syndrome","X-linked alpha-thalassemia/mental retardation syndrome (ATR-X syndrome) is a rare syndromic form of X-linked mental retardation. It is characterized by severe mental retardation in males, characteristic facial appearance, alpha thalassaemia, genital anomalies, skeletal abnormalities, and characteristic posture and/or behavior. ATR-X syndrome is caused by a mutation in the ATRX gene, a critical factor involved in heterochromatin formation at mammalian centromeres and telomeres.","Congenital malformation"
"H01560","Alkhumra hemorrhagic fever","Alkhumra hemorrhagic fever is a severe, often fatal, infectious disease caused by Alkhumra hemorrhagic fever virus (AHFV), a flavivirus in the Flaviviridae family of +ssRNA viruses, and transmitted by Ixodoidea ticks. AHFV was first isolated in 1994-1995 in the Al Khumra district, Jeddah, Saudi Arabia. Full genome sequencing has indicated that AHFV is a distinct variant of Kyasanur Forest disease virus.","Infectious disease"
"H01938","Hypermanganesemia with dystonia","Hypermanganesemia with dystonia (HMNDYT) is an autosomal recessive disorder of manganese (Mn) homeostasis. Loss-of-function mutations in SLC30A10, a Mn efflux transporter, or SLC39A14, a Mn influx transporter, increase Mn levels in blood and brain, and induce severe neurotoxicity.","Hematologic disease"
"H01104","Loiasis","Loiasis is an infection with Loa loa, a filarial parasite found in central Africa transmitted by Chrysops fly bites. Loiasis is often asymptomatic.","Infectious disease"
"H01336","Encephalitozoon infection","The genus Encephalitozoon are spore-forming obligate intracellular microsporidian parasites that infect a wide range of organisms, including protists, invertebrates, humans, and many other vertebrates and known as opportunistic pathogen associated with immunocompromised individuals. Major symptoms include a life-threatening chronic diarrhea and systemic disease. The transmission routes may involve person-to-person as well as waterborne or foodborne, especially in developing countries with poor sanitation. E. intestinalis is recognized as one of the most frequently identified microsporidia in humans.","Infectious disease"
"H00479","Metaphyseal dysplasias","Metaphyseal dysplasias are very rare skeletal disorders with short limb/short stature phenotypes. Defects in metaphyseal development leads to enlarged metaphyses of long bones that tend to fracture in these diseases.","Congenital malformation"
"H01799","Vibratory urticaria","Vibratory urticaria is a rare type of physical skin reactivity characterized by the occurrence of local erythematous, edematous, cutaneous and subcutaneous lesions that result from stimuli of a vibratory nature. A local stimulus of sufficient intensity will also result in generalized or facial erythema accompanied by a transient headache. The histamine release that is associated with urticarias has implicated aberrant degranulation of mast cells in their pathogenesis. A missense variant in ADGRE2 gene has been found in families with vibratory urticaria, implicating the encoded adhesion G-protein-coupled receptor (GPCR) as a mechanosensor in mast cells.","Skin and connective tissue disease"
"H00821","Age-related macular degeneration","Macular degeneration is the physical breakdown of the central portion of the retina called the macula. Age-related macular degeneration (AMD/ARMD) is the leading cause of blindness. AMD is a complex disease caused by the combination of genetic predisposition and environmental factors. Using genome linkage scan and association studies, multiple potentially causative genes have been identified. In AMD, there are two phenotypes, atrophic/ dry and neovascular/ wet. The former is characterized by the geographic atrophy due to death of retinal pigment epithelium, and the latter is usually characterized by the abnormal growth of new blood vessels under the macula, which causes severe loss of vision. While wet AMD can be treated by the inhibition of vascular endothelial growth factor or photodynamic therapy, so far there are no available treatments for dry AMD.","Nervous system disease"
"H01309","Sarcoidosis, early-onset","Early-onset sarcoidosis (EOS) is a special subtype of sarcoidosis, a systematic inflammatory disease with unknown etiology. It occurs in children younger than 4 years of age and is characterized by a distinct triad of skin, joint, and eye disorders without apparent pulmonary involvement. Mutations in the gene encoding NOD2 in humans have been associated with EOS. NOD2 is an intracellular microbial sensor of the innate immune system that can act as a potent activator and regulator of inflammation.","Immune system disease"
"H01907","Acid-labile subunit deficiency","Acid-labile subunit (ALS) deficiency is characterized by severe reduction of IGF-I and IGFBP-3 that remain low after GH treatment, associated with mild growth retardation. ALS, encoded by the IGFALS gene, is mainly produced by the liver. The patients were found to be carriers for IGFALS gene mutations. ALS protein is a key component of the circulating IGF ternary complex. The main role of ALS is the extension of IGF-I half life by protecting it from degradation and preventing the passage of IGF-I to the extravascular compartment.","Endocrine disease"
"H01331","Dental caries","Dental caries occurs due to demineralization of enamel and dentine (the hard tissues of the teeth) by organic acids formed by bacteria in dental plaque through the anaerobic metabolism of sugars derived from the diet. The 2 primary bacteria involved in caries formation are mutans streptococci and lactobacilli. When sugars or other fermentable carbohydrates are ingested, the resulting fall in dental plaque pH caused by organic acids increases the solubility of calcium hydroxyapatite in the dental hard tissues and demineralization occurs as calcium is lost from the tooth surface. The pH at which demineralization occurs is often referred to as the critical pH and is approximately 5.5.","Infectious disease"
"H01103","Alpha-1-antitrypsin deficiency","Alpha-1-antitrypsin (A1AT) deficiency is a genetic disorder characterized by low plasma levels of A1AT. The condition is associated with emphysematous lung disease and also with liver disease. A1AT is the archetype of the serine protease inhibitor. Mutations in the A1AT gene lead to misfolding of the protein and accumulation within the endoplasmic reticulum of hepatocytes. The accumulation of mutant A1AT protein has a directly toxic effect on the liver, resulting in hepatitis and cirrhosis. And the decrease in circulating A1AT results in protease-antiprotease imbalance at the lung surface and emphysema ensues.","Inherited metabolic disease; Lung disease; Liver disease"
"H01567","Thiamine pyrophosphokinase deficiency","Thiamine pyrophosphokinase (TPK) deficiency is a recently described rare disorder that present as episodic encephalopathy or Leigh syndrome like early-onset global developmental delay. TPK deficiency is one of thiamine metabolism dysfunction syndrome caused by mutations TPK1. TPK produces thiamine pyrophosphate (TPP). TPP is a cofactor for enzymes important in a range of fundamental processes such as cellular respiration. It has been reported that early thiamine supplementation prevented encephalopathic episodes and improved developmental progression.","Inherited metabolic disease"
"H00687","Fraser syndrome","Fraser syndrome or cryptophthalmos is a rare autosomal recessive disorder characterized by major features such as cryptophthalmos with completely fused eyelids, partial syndactyly, renal abnormalities, and genital malformations.","Congenital malformation"
"H01755","Apert syndrome","Apert syndrome is a rare autosomal dominant disorder characterized by craniosynostosis, severe syndactyly of hands and feet, and dysmorphic facial features. Other frequent complications include cleft palate and learning disability. Over 98% of cases are caused by specific missense mutations of FGFR2, either Ser252Trp or Pro253Arg.","Congenital malformation"
"H02316","Adrenal insufficiency, NR5A1 related","NR5A1, also termed steroidogenic factor 1 (SF-1), is a nuclear receptor and a key transcriptional regulator of genes involved in the hypothalamic-pituitary-steroidogenic axis. There are some known mutations of the NR5A1 gene in humans. A few of them were originally identified in patients with adrenal insufficiency. In 46,XY individuals, NR5A1-related phenotypes may range from disorders of sex development (DSD) to oligo/azoospermia, and in 46,XX individuals, from 46,XX ovotesticular and testicular DSD to primary ovarian insufficiency.","Endocrine and metabolic disease"
"H00441","Progressive osseous heteroplasia","Progressive osseous heteroplasia (POH) is a genetic disorder where heterozygous inactivating mutations in the GNAS gene have been identified. Patients with POH characteristically develop extensive bone formation within the superficial dermal layer of the skin.","Musculoskeletal disease"
"H01593","Osteoporosis","Osteoporosis is a common disease characterised by a generalised reduction in bone mineral density (BMD), microarchitectural deterioration of bone tissue and an increased risk of fracture. Since BMD values fall progressively with age, the prevalence of osteoporosis increases with age. It has been estimated that approximately 50% of all women will have osteoporosis by the age of 80. Studies in twins and families indicate that genetic factors play an important role in the regulation of BMD and other determinants of osteoporotic fracture risk. Osteoporosis is a polygenic disorder, determined by the effects of several genes, each with relatively modest effects. Population-based studies and case-control studies have similarly identified polymorphisms in several candidate genes that have been associated with bone mass or osteoporotic fracture, including the vitamin D receptor, oestrogen receptor and collagen gene. Bisphosphonates, and in some patients denosumab, are first-line drugs for osteoporosis.","Musculoskeletal disease"
"H00673","Weill-Marchesani syndrome","Weill-Marchesani syndrome (WMS) is a rare connective tissue disorder characterized by short stature, brachydactyly, ectopia lentis and spherophakia. Decreased joint flexibility is one of the features of this syndrome.","Congenital malformation"
"H02124","Interstitial lung and liver disease","Interstitial lung and liver disease (ILLD) is an autosomal recessive severe childhood form of pulmonary alveolar proteinosis. The main symptom is respiratory insufficiency, often leading to death in childhood or adolescence as a result of lung fibrosis. In addition to lung fibrosis, non-life-threatening liver involvement might be present, as indicated by elevated enzymes, steatosis, fibrosis, or cirrhosis. The mutations in MARS associated with ILLD have been reported.","Respiratory disease"
"H00217","Pulmonary alveolar proteinosis","Pulmonary alveolar proteinosis (PAP) is a rare but potentially treatable disease, characterized by impaired surfactant metabolism that leads to accumulation in the alveoli of proteinaceous material rich in surfactant protein and its component. PAP is classified into 2 main types, congenital and acquired. The acquired form is subdivided into the autoimmune form and the secondary form. The vast majority of PAP occurs as an autoimmune PAP. In autoimmune PAP, patients generate antibodies against the granulocyte macrophage colony stimulating factor (GM-CSF) protein. Whole-lung lavage is the most widely accepted therapy for symptomatic PAP. Recent data suggest that exogenous GM-CSF therapy has potential in the treatment of autoimmune PAP. Congenital PAP is also known as pulmonary surfactant metabolism dysfunction (SMDP).","Respiratory disease"
"H00819","Stargardt disease","Stargardt disease (STGD) is the most common type of hereditary macular dystrophy. It is characterized by decreased central vision, atrophy of the macula and underlying retinal pigment epithelium (RPE), and frequent presence of prominent flecks in the posterior pole of the retina. Histopathologically, eyes with STGD reveal abnormal accumulations of lipofuscin in the RPE. To date, mutations in four genes have been identified as causing STGD, including ABCA4, ELOVL4, PROM1, and CNGB3.","Nervous system disease"
"H00025","Penile cancer","Penile cancer is a disease with a high morbidity and mortality. Its prevalence is relatively rare in developed countries but more common in South America and East Africa. Squamous cell carcinoma (SCC) is the predominant tumor type in penile cancer, accounting for 95% of cases. Penile cancers are thought to arise from the progression of precursor lesions and can be subdivided into human papilloma virus (HPV) positive and HPV negative cases. Most common disrupted pathways, both in HPV-mediated and HPV-independent penile carcinogenesis, involve the p14ARF/MDM2/p53 and/or p16INK4a/cyclin D/Rb pathways. HPVs exert their oncogenic effect by expressing the oncoproteins E6 and E7, which bind to and inactivate the p53 and Rb tumor suppressor gene products, respectively. HPV independent mechanisms of pathway inactivation include silencing of the p16INK4a gene by promoter hypermethylation, somatic mutations of the p53 gene, over-expression of MDM2 and mutation of p14ARF. Several other molecular events include alterations in the activity and/or expression of ras and myc genes, cyclo-oxygenase-2 (COX) pathway and prostaglandin E2 synthase. These alterations have been described in both HPV-positive and -negative penile cancers.","Cancer"
"H01558","Parathyroid carcinoma","Parathyroid carcinoma (PC) is a highly aggressive endocrine tumor, with an annual incidence of less than 1 per million. Over 90% of patients present with excess parathyroid hormone (PTH), representing <1-5% of all patients with primary hyperparathyroidism. PC is associated with mutations in the HRPT2/CDC73 gene and with decreased parafibromin and calcium-sensing receptor (CASR) expression. Negative parafibromin staining together with a CDC73 gene mutation increases the likelihood of malignancy and also predicts the clinical outcome, namely local invasion and/or metastases and mortality. An increased mortality is predicted by either of these abnormality combined with down regulation of the calcium-sensing receptor (CaSR) expression.","Cancer"
"H01900","Encephalopathy due to defective mitochondrial and peroxisomal fission","Encephalopathy due to defective mitochondrial and peroxisomal fission (EMPF) is a very rare lethal disorder characterized by cerebral dysgenesis, hypotonia, seizures, lactic acidosis, elevated very long chain fatty acids, and abnormally elongated mitochondria and peroxisomes. It has been described that patients have mutations in DNM1L gene, which has a critical role in regulating the fission of both mitochondria and peroxisomes. Recently, it has been reported that mutations in mitochondrial fission factor (MFF) also cause Leigh-like encephalopathy, optic atrophy and peripheral neuropathy.","Inherited metabolic disease; Nervous system disease; Mitochondrial disease"
"H00826","Blepharophimosis-ptosis-epicanthus inversus syndrome","Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a rare autosomal dominant disease. The cardinal feature of this disease is a complex eyelid/ocular malformation such as blepharophimosis, ptosis, epicanthus inversus and telecanthus. The horizontal shortening of the palpebral aperture can lead to amblyopia. It is caused by mutations in FOXL2 gene that is involved in palpebral and ovarian development. Some of the female patients have premature ovarian failure (POF) and this condition is classified as BPES type I. BPES with normal ovarian function is referred to as BPES type II.","Congenital malformation"
"H00228","Thalassemia","Thalassemia is the most common hereditary blood disease caused by mutation of genes encoding hemoglobin alpha and beta chains. The anemia that is associated with thalassemia is caused by ineffective erythropoiesis which results from apoptosis of erythroid precursors or hemolysis due to the chain imbalances.","Hematologic disease"
"H02329","Hepatic lipase deficiency","Hepatic lipase deficiency is a rare autosomal recessive disorder, characterized by elevated levels of triglycerides and cholesterol. Some patients have premature cardiovascular disease. Missense mutations in LIPC have been identified to be responsible for this disease.","Endocrine and metabolic disease"
"H01551","Interstitial cystitis","Interstitial cystitis (IC), also referred to as bladder pain syndrome (BPS), is a chronic non-infectious inflammatory condition characterized by recurring discomfort, pain or pressure in the bladder and the surrounding pelvic region. IC/BPS most often affect females compared with males. The affected individuals experience urinary frequency and urgency. The duration of irritative symptoms associated with unpleasant sensation are longer than six weeks duration. At present, there are two major subtypes of IC/BPS: those with or without Hunner lesion, which are also known as ulcerative or non-ulcerative IC/BPS, respectively.","Urinary system disease"
"H00483","Angel shaped phalangoepiphyseal dysplasia","Angel shaped phalangoepiphyseal dysplasia (ASPED) is one type of osteochondrodysplasia characterized by angel shaped middle phalanges and generalized epiphyseal dysplasia that disproportionately affects the middle phalanx and distal hip joint.","Congenital malformation"
"H01763","Porphyria","Porphyria is an inborn error of heme biosynthesis porphyrin metabolism caused by deficiency of enzymes of porphyrin metabolism. The intermediates of this pathway (porphyrinogens, porphyrins and their precursors) are produced in excess and accumulate in tissues, resulting in neurological and/or photocutaneous symptoms, and hematological disturbances. Porphyrias are divided into erythropoietic and hepatic according to the predominant porphyrin-accumulating tissue. Erythropoietic porphyrias include erythropoietic protoporphyria (EPP), congenital erythropoietic porphyria (CEP), and the very rare hepatoerythropoietic porphyria (HEP). Hepatic porphyrias include ALA-dehydratase deficiency porphyria (ADP), acute intermittent porphyria (AIP), porphyria cutanea tarda (PCT), hereditary coproporphyria (HCP), and variegate porphyria (VP). Recently, a new type of erythroid porphyria, X-linked dominant protoporphyria (XLDPP) has been reported.","Inherited metabolic disease"
"H01307","Nonsyndromic congenital nail disorder","Nonsyndromic congenital nail disorder (NDNC) is rare and has been reported in only a small number of families. There is variable expression of nail phenotypes among individuals. It have identified that mutations in the RSPO4 and FZD6, components of the Wnt pathway, cause the hypoplastic nail disorders. Hereditary leukonychia is caused by mutations in PLCD1. Defects in COL7A1 can cause heterogeneous clinical phenotypes extending from simple toe nail dystrophy without skin fragility to typical dominant dystrophic epidermolysis bullosa.","Skin disease"
"H01909","Hypoinsulinemic hypoglycemia with hemihypertrophy","Hypoinsulinemic hypoglycemia with hemihypertrophy (HIHGHH) is characterized by hemihypertrophy without any other features of Beckwith-Wiedemann syndrome [DS:H00713] and persistent hypoketotic, hypofattyacidemic hypoinsulinaemic hypoglycemia with no detectable incompletely processed high molecular weight IGF-II precursor proteins or insulin autoantibodies. There is not evidence of increased glucose clearance from the circulation. Patients have been found to carry a de novo mutation in the serine/threonine kinase AKT2.","Inherited metabolic disease"
"H01135","Ribose 5-phosphate isomerase deficiency","Ribose 5-phosphate isomerase (RPI) deficiency is a very rare enzymopathy of the pentose phosphate pathway with one sole diagnosed case. The patient presented with progressive leukoencephalopathy and peripheral neuropathy. Systematic metabolic profiling identified elevated levels of arabitol and ribitol in affected brain regions and body fluids. RPI gene-sequence analysis revealed a frameshift and a missense mutation.","Inherited metabolic disease; Nervous system disease"
"H00221","Combined deficiency of factors V and VIII","Combined deficiency of factors V and VIII (F5F8D) is caused by mutations in LMAN1 or MCFD2, which form a complex working as an cargo receptor for transport of coagulation factors V and VIII from ER to Golgi.","Hematologic disease"
"H00013","Small cell lung cancer","Lung cancer is a leading cause of cancer death among men and women in industrialized countries. Small cell lung carcinoma (SCLC) is a highly aggressive neoplasm, which accounts for approximately 25% of all lung cancer cases. Molecular mechanisms altered in SCLC include induced expression of oncogene, MYC, and loss of tumorsuppressor genes, such as p53, PTEN, RB, and FHIT. The overexpression of MYC proteins in SCLC is largely a result of gene amplification. Such overexpression leads to more rapid proliferation and loss of terminal differentiation. Mutation or deletion of p53 or PTEN can lead to more rapid proliferation and reduced apoptosis. The retinoblastoma gene RB1 encodes a nuclear phosphoprotein that helps to regulate cell-cycle progression. The fragile histidine triad gene FHIT encodes the enzyme diadenosine triphosphate hydrolase, which is thought to have an indirect role in proapoptosis and cell-cycle control.","Cancer"
"H00477","Pseudoachondroplasia","Pseudoachondroplasia (PSACH) is a condition with short-limb, short stature, joint pain, and early-onset osteoarthrosis caused by epiphyseal ossification delay. PSACH is caused by mutations in COMP.","Congenital malformation"
"H02320","Vacuolar myopathy with CASQ1 aggregates","Vacuolar myopathy with CASQ1 aggregates (VMCQA) is an autosomal dominant benign vacuolar myopathy and hyperCKemia. VMCQA is the protein aggregate myopathy with benign evolution and muscle inclusions composed of excess CASQ1. Mutations in the CASQ1 gene  have been found in patients with VMCQA.","Musculoskeletal disease"
"H02112","Persistent hyperplastic primary vitreous","Persistent hyperplastic primary vitreous (PHPV), also known as persistent fetal vasculature, is a rare congenital developmental malformation of the eye, caused by the failure of regression of the primary vitreous. PHPV typically presents unilaterally without association with systemic findings, but sometimes PHPV may be associated with rare systemic syndromes. Most cases of PHPV are sporadic, but it can be inherited as an autosomal dominant or recessive trait.","Nervous system disease"
"H01797","Webb-Dattani syndrome","Webb-Dattani syndrome is an autosomal recessive disorder characterized by secondary (post-natal) microcephaly with fronto-temporal lobe hypoplasia, multiple pituitary hormone deficiency, seizures, severe visual impairment, and abnormalities of the kidneys and urinary tract. A homozygous frameshift mutation in the basic HLH transcription factor ARNT2 has been revealed in affected individuals.","Congenital malformation"
"H00645","Incontinentia pigmenti","Incontinentia pigmenti is an X-linked dominant genodermatosis mostly affecting females. Cutaneous manifestations are present along the lines of Blaschko and are subdivided into four stages: vesicular, verrucous, hyperpigmented, and atrophic. Other tissues of ectodermal origin are also affected, showing hair abnormalities, dental anomalies, and ophthalmologic and neurologic alterations. Familial incontinentia pigmenti is caused by mutations in the NEMO gene.","Congenital malformation"
"H01936","Hyperbiliverdinemia","Hyperbiliverdinaemia (HBLVD) is a clinical sign that has been infrequently reported in cases of liver cirrhosis or liver carcinoma, usually indicating a poor long-term prognosis. Under physiological circumstances, the concentrations of biliverdin are much lower than those of bilirubin. However, in rare cases, impairment of the biliverdin/bilirubin pathway has been reported to result in green jaundice and a green discoloration of body fluids. It has been reported that hyperbiliverdinaemia is caused by a genetic defect in the BLVRA gene in conjunction with decompensated liver cirrhosis.","Metabolic disease; Hematologic disease"
"H01338","Myosclerosis","Myosclerosis is an autosomal recessive disorder caused by nonsense mutation of COL6A2. This disease is one of the collagen VI myopathies, characterized by difficulty in walking in early childhood, toe walking, and progressive contractures of calf muscles. In the early 30s the muscles are slender with a firm woody consistency and associated with contractures that restrict range of motion of many joints.","Nervous system disease; Musculoskeletal disease"
"H00448","Familial osteochondritis dissecans","Osteochondritis dissecans is defined as a separation of articular cartilage and subchondral bone from the joint surface, affecting the knee, ankle and elbow joints. The disease is caused by heterozygous missense mutation in Aggrecan (ACAN) which is a major cartilage component.","Musculoskeletal disease"
"H00810","Progressive myoclonic epilepsy","Progressive myoclonic epilepsy (EPM) is a syndrome complex characterized by progressive myoclonus, cognitive impairment, ataxia, and other neurologic deficits. PME is a disease that afflicts previously normal children with ever-worsening and soon-intractable myoclonus and epilepsy, usually associated with neurodegeneration, and eventual dementia and early death. PME include Lafora disease, Unverricht-Lundborg disease, the neuronal ceroid lipofuscinoses, type I sialidosis (cherry-red spot myoclonus), Dentatorubro-pallidoluysian atrophy (DRPLA), and type III Gaucher disease. Almost all the autosomal recessively inherited PMEs are lysosomal diseases, with the exception of Lafora disease in which neither the accumulating material nor the gene products are in lysosomes. PME also occurs in various forms of mitochondrial encephalomyopathies, especially in myoclonic epilepsy with ragged-red fibers (MERRF).","Nervous system disease"
"H02115","Congenital aural atresia","Congenital aural atresia (CAA) is an autosomal dominant defect that is characterized by hypoplasia of the external auditory canal, often in association with dysmorphic features of auricle, middle ear, and, occasionally, the inner ear structures. Recently, heterozygous mutations in TSHZ1 was described to cause CAA in human. TSHZ1 has been shown to be important for murine middle-ear development.","Congenital malformation"
"H01790","Emanuel syndrome","Emanuel syndrome (ES) is a rare anomaly characterized by a distinctive phenotype, consisting of characteristic facial dysmorphism, microcephaly, severe mental retardation, developmental delay, renal anomalies, congenital cardiac defects, and genital anomalies in boys. Patients have a supernumerary derivative chromosome caused by a parental balanced translocation between chromosomes 11 and 22.","Chromosomal abnormality"
"H00642","Lacrimo-auriculo-dento-digital syndrome","Lacrimo-auriculo-dento-digital (LADD) syndrome is an autosomal dominant disorder characterizd by hypoplasia or aplasia of the lacrimal and salivary glands, cup shaped pinnae with sensorineural deafness, dental abnormalities with small teeth, and radial ray abnormalities in hands.","Congenital malformation"
"H00470","Acromesomelic dysplasia, Maroteaux type","Acromesomelic dysplasia, Maroteaux type is an autosomal recessive skeletal dysplasia that affects postnatal skeletal growth. Affected indivisials show marked short stature and limb shortening. Homozygous loss-of-function mutations in NPR2 have been identified.","Congenital malformation"
"H02327","KBG syndrome","KBG syndrome is characterized by intellectual disability, skeletal malformations, and macrodontia. It has been reported that mutations in ANKRD11 cause this disease.","Congenital malformation"
"H00828","Familial cylindromatosis","Familial cylindromatosis is a rare, autosomal dominant disorder characterized by the development of multiple benign tumors originating from the skin appendages. It is linked to CYLD gene, whose loss of function impairs epidermal differentiation.","Skin and connective tissue disease"
"H00014","Non-small cell lung cancer","Lung cancer is a leading cause of cancer death among men and women in industrialized countries. Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer and represents a heterogeneous group of cancers, consisting mainly of squamous cell (SCC), adeno (AC) and large-cell carcinoma. Molecular mechanisms altered in NSCLC include activation of oncogenes, such as K-RAS, EGFR and EML4-ALK, and inactivation of tumorsuppressor genes, such as p53, p16INK4a, RAR-beta, and RASSF1. Point mutations within the K-RAS gene inactivate GTPase activity and the p21-RAS protein continuously transmits growth signals to the nucleus. Mutations or overexpression of EGFR leads to a proliferative advantage. EML4-ALK fusion leads to constitutive ALK activation, which causes cell proliferation, invasion, and inhibition of apoptosis. Inactivating mutation of p53 can lead to more rapid proliferation and reduced apoptosis. The protein encoded by the p16INK4a inhibits formation of CDK-cyclin-D complexes by competitive binding of CDK4 and CDK6. Loss of p16INK4a expression is a common feature of NSCLC. RAR-beta is a nuclear receptor that bears vitamin-A-dependent transcriptional activity. RASSF1A is able to form heterodimers with Nore-1, an RAS effector. Therefore loss of RASSF1A might shift the balance of RAS activity towards a growth-promoting effect.","Cancer"
"H00226","Glanzmann thrombasthenia","Glanzmann thrombasthenia is a rare autosomal recessive bleeding syndrome affecting the megakaryocyte lineage and characterized by lack of platelet aggregation. This disease is caused by mutation in the integrin family receptor genes encoding platelet glycoprotein alpha-IIb or platelet glycoprotein IIIa.","Hematologic disease"
"H01132","Aplastic anemia","Aplastic anemia (AA) is a rare disease in which the reduction of the circulating blood cells results from damage to the stem cell pool in bone marrow. Most cases of acquired aplastic anemia are the consequence of an immune-mediated destruction of hematopoiesis. Autoreactive cytotoxic T cells play a key role in the pathogenesis of AA by myelosuppressive cytokines including interferon-gamma. It has been reported that polymorphisms in IFNG are related to AA. A minority of patients with AA has heterozygous mutations in genes encoding the telomerase components TERT or TERC. Immunosuppressive therapy (IST) is one of the main treatment modalities for AA, although most patients with telomerase mutations do not respond adequately to IST.","Hematologic disease"
"H01764","Polysplenia syndrome","Polysplenia syndrome (PSS) is a rare subtype of heterotaxy syndrome with multiple spleens. It has been reported that most patients die before 5 years of age because the disease is often associated with congenital anomalies, such as cardiovascular anomalies. Some patients have a normal heart or only minor cardiac defects, are often diagnosed incidentally in patients being treated for other disease. The patient has bilateral bilobed lungs with hyparterial bronchi, abnormal location of abdominal solid organs and malrotation of bowels with multiple spleens. The etiology of PSS is not known yet. The causative factors of PSS are thought to be association of embryonic, genetic and teratogenic components.","Congenital malformation"
"H01556","Meningioma","Meningiomas are the second-most common central nervous system tumor in adults. These tumors arise from arachnoid cells of the meninges, the covering layer of the brain. The majority of meningiomas tend to be benign, localized, and non-invasive. However, some meningiomas tend to be more aggressive with tendencies toward invasion of the surrounding brain, high propensity for recurrence, and in rare cases extracranial metastasis. Hereditary factors and ionizing radiation play an important role in the initiation of at least some meningiomas. Inactivation of the NF2 tumor suppressor gene is likely responsible for the initiation of more than half of all meningiomas and may cause a mesenchymal-like cytomorphology. Recently, novel mutations have been discovered in non-NF2 meningiomas. The somatic mutations in components of the SHH-GLI1 and AKT1-MTOR signaling pathways indicates the potential for cross talk of these pathways in the development of meningiomas.","Cancer"
"H00484","Multiple synostosis syndrome","Proximal symphalangism is a condition characterized by variable fusion of the proximal interphalangeal joints. Multiple synostosis syndrome (SYNS) is a more severe form of proximal symphalangism with additional bone fusions involving carpal, tarsal, and other joints.","Congenital malformation"
"H00219","Hemophilia","Hemophilia A and B are X-linked recessive disorders which are the most common hereditary hemorrhagic disorders caused by a deficiency or dysfunction of blood coagulation factor VIII (FVIII) and factor IX (FIX), respectively. Von Willebrand disease is caused by quantitative and/or qualitative defects of von Willebrand factor and inherited in both autosomal dominant and recessive manner.","Hematologic disease"
"H00817","Branchiooculofacial syndrome","Branchiooculofacial syndrome (BOFS) is an autosomal dominant condition characterized by branchial cleft sinus defects associated with rotated auricles with stenotic auditory canals and conductive hearing loss. Branchial skin lesions covering branchial remnants are noted. Ocular anomalies and characteristic facial appearance including cleft lip/cleft palate together constitute the disease.","Congenital malformation"
"H02318","Palmoplantar hyperkeratosis with squamous cell carcinoma of skin and sex reversal","Palmoplantar hyperkeratosis with squamous cell carcinoma of skin and sex reversal (PPK-SCC) is a form of 46,XX disorder of sex development. It is a rare autosomal recessive disorder caused due to biallelic loss of function mutations in RSPO1 gene. RSPO1 is one of the most important genes controlling female gonadal differentiation.","Reproductive system disease"
"H01569","CHOPS syndrome","CHOPS syndrome is a congenital disorder involving multiple abnormalities. The symptoms include cognitive impairment, coarse facies, heart defects, obesity, pulmonary involvement, short stature, and skeletal dysplasia. The gain-of-function mutations in the AFF4 gene, encoding a critical component of the super elongation complex (SEC), cause CHOPS syndrome. While CHOPS syndrome and Cornelia de Lange syndrome are clinically recognizable distinct entities there is some phenotypic overlap between these two diagnoses.","Congenital malformation"
"H00689","Delayed sleep phase syndrome","Delayed sleep phase syndrome (DSPS) is characterized by a 3 to 6-hour delayed sleep schedule relative to the desired. The single nucleotide polymorphism (Ala129Thr) in Arylalkylamine N-acetyltransferase (AANAT), a rate-limiting enzyme in melatonin synthesis, has been identified in patients with delayed sleep phase disorder.","Nervous system disease"
"H01931","Lethal-type popliteal pterygium syndrome","Lethal-type popliteal pterygium syndrome (LPPS), described as an autosomal-recessive form of popliteal pterygium syndrome (PPS) and also known as Bartsocas-Papas syndrome (BPS), is characterized by a more severe phenotype than that associated with the autosomal-dominant form. LPPS is characterised by multiple popliteal pterygia, cutaneous syndactyly, lack of nails, ankyloblepharon, filiform bands between the jaws, hypoplastic external genitalia, cleft lip and/or palate, and fetal or neonatal lethality, although, in the latter case, survival into childhood and beyond has been reported. It has been shown that recessive mutations in RIPK4 cause LPPS.","Congenital malformation"
"H01720","Southeast Asian ovalocytosis","Southeast Asian ovalocytosis (SAO) is a very common condition in the aboriginal peoples from Papua New Guinea, Indonesia, Malaysia, the Philippines, and southern Thailand, in areas where malaria is endemic, with prevalence varying between 5% and 25%. SAO is now known to be caused by a 27 base-pair deletion in SLC4A1, which codes for band 3, a 911 amino acid protein that is both a structural component of the red cell membrane cytoskeleton and the chloride-bicarbonate anion-exchanger in this membrane. SAO is believed to have evolved because these parts of Southeast Asia historically have had a high incidence of Plasmodium falciparum malaria, against which SAO offers clinical protection. Individuals with SAO are characterized as having oval-shaped red blood cells with increased membrane rigidity and decreased anion transport, but no clinical symptoms beyond sporadic associations with anemia in both adults and neonates. The diagnosis is made accidentally as a result of a peripheral blood smear examination, showing the characteristic rounded elliptocytes (ovalocytes).","Hematologic disease"
"H01512","Langerhans cell histiocytosis","Langerhans cell histiocytosis (LCH) is a rare histiocytic disorder characterized by a clonal proliferation of specialized cells with characteristics resembling antigen-presenting cells that reside in the skin and mucosa. Its clinical presentation is variable and ranges from isolated skin or bone disease to a life-threatening multisystem condition. Historically, it has been hypothesized that the disease originated from epidermal Langerhans cells. However, new evidence supports a model in which LCH occurs as a consequence of a misguided differentiation programme of myeloid dendritic cell precursors. In LCH, there is a very high frequency of activating mutations in MAPK signaling pathway genes, most notably BRAF-V600E, as well as MAP2K1. Genetic, molecular and functional data implicate activation of the MAPK (ERK) signalling pathway at critical stages in myeloid differentiation as an essential and universal driver of LCH pathology.","Cancer"
"H02397","Neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features","Neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features (NEDMAGA) is an autosomal dominant disorder caused by a recurrent de novo nonsense variant in ZSWIM6. Patients have severe-profound intellectual disability and additional central and peripheral nervous system symptoms but an absence of frontonasal or limb malformations.","Mental and behavioural disorder"
"H01176","Uncomplicated urinary tract infection","Staphylococci are widespread as commensals of humans and animals where they colonize the skin or mucous membranes. Staphylococcus saprophyticus is a coagulase-negative Staphylococcus, gram-positive uropathogen and frequently isolated from young female outpatients presenting with uncomplicated urinary tract infections. S. saprophyticus causes uncomplicated urinary tract infection (UTI) but no severe bacterial infectious disease as caused by S. aureus. The urease of S. saprophyticus is known to be a virulent factor for the persistent infection in the urinary tract. All of the virulence factors of S. aureus, such as coagulase, hemolysins, enterotoxins, extracellular matrixbinding proteins, and exoenzymes, are absent in the S. saprophyticus genome. Besides S. saprophyticus is a leading gram-positive uropathogen of uncomplicated UTI, a restricted group of gram-negative bacteria, including Escherichia coli, Proteus mirabilis, and Klebsiella spp. is often observed to cause uncomplicated UTI.","Infectious disease"
"H00898","Myopathy with lactic acidosis and sideroblastic anaemia","Myopathy with lactic acidosis and sideroblastic anaemia (MLASA) is a rare autosomal recessive oxidative phosphorylation disorder specific to skeletal muscle and bone marrow. MLASA has been associated with a missense mutation in pseudouridylate synthase 1 (PUS1), an enzyme located in both nucleus and mitochondria, which converts uridine into pseudouridine in several cytosolic and mitochondrial tRNA positions and increases the efficiency of protein synthesis in both compartments. Recentry, it has been reported that a mutation of the mitochondrial tyrosyl-tRNA synthetase gene, YARS2, also causes MLASA. Myopathy with succinate dehydrogenase and aconitase deficiency has been found to be caused by mutations in the gene encoding the iron-sulphur cluster scaffold protein (ISCU). ISCU is essential for the activity mitochondrial iron-sulphur proteins such as succinate dehydrogenase and aconitase.","Congenital disorder of metabolism"
"H01344","Nijmegen syndrome","Nijmegen Breakage syndrome (NBS) is a rare autosomal recessive disorder characterized by microcephaly, growth retardation, immunodeficiency, radiosensitivity, and cancer predisposition. Due to a founder mutation in the NBN gene, the disease is encountered most frequently among Slavic populations. Recently, a disease due to RAD50 deficiency has been reported. The patient displayed symptoms similar to NBS, microcephaly, mental retardation, bird-like face, and short stature. The MRE11/RAD50/NBN (MRN) complex plays a key role in recognizing and signaling DNA double-strand breaks.","Immune system disease"
"H00296","Defects in RecQ helicases","RecQ helicases have crucial roles in the maintenance of genome stability. In humans, it is known that deficiencies in three of the five human RecQ helicases cause genetic disorders characterized by cancer predisposition, premature aging and developmental abnormalities. These disorders are Bloom's syndrome (BS), Werner's syndrome (WS), and Rothmund-Thomson syndrome (RTS), which are caused by mutations in BLM, WRN and RECQ4, respectively. Despite the apparent structural and biochemical similarities between the BLM, WRN and RECQ4 proteins, the phenotypes of BS, WS and RTS are different, suggesting that each disease pathway is functionally distinct to some extent. BS is characterized by most prominently, a predisposition to all types of cancers. WS is characterized by the premature development of features that resemble aging. RTS is characterized by skin and skeletal abnormalities, signs of premature aging, and cancer predisposition, especially to osteosarcomas. Recent research has shown many connections between all three proteins and the regulation of excess HR (Homologous recombination). It was also indicated that BLM is involved in repair of stalled DNA replication forks, and that WRN is required for telomere maintenance. Mutations in RECQL4 also associate with 2 additional syndromes, Rapadilino and Baller-Gerold syndrome.","Congenital malformation"
"H01182","Biotinidase deficiency","Biotinidase deficiency is an autosomal recessive metabolic disorder in which the biotinidase is defective and the biotin is not recycled. Patients often exhibit feeding or breathing difficulties, skin rash, alopecia, hypotonia and seizures. Biotin treatment can ameliorate or prevent symptoms.","Inherited metabolic disease"
"H00050","Synovial sarcoma","Synovial sarcomas account for 7% to 10% of all human soft-tissue sarcomas. The tumors arise at any age, but affect mainly young adults and more commonly males. Clinically, they appear as deep-seated slowly growing masses. In more than half of the cases, metastases develop, primarily to the lungs but also to the lymph nodes and bone marrow. A specific translocation, t(X; 18)(p11.2; q11.2), is found in more than 90% of reported synovial sarcoma, including biphasic, monophasic, and poorly differentiated tumors. The breakpoints of the t(X; 18) have been cloned and shown to involve the fusion of the SYT gene at 18q11 to either of two highly homologous genes at Xp11 called SSX1 and SSX2. The SYT-SSX1 fusion is associated with biphasic morphology and a worse prognosis, whereas the SYT-SSX2 fusion tends to show monophasic morphology and better outcome.","Cancer"
"H00262","Spina bifida","Spina bifida is among the phenotypes of the larger condition known as neural tube defects (NTDs). It is a group of congenital defects of closure of one or more vertebral arches. NTDs can occur in two major forms: spina bifida aperta, which is the open-lesion NTD, and the closed-lesion NTD, more commonly known as spina bifida occulta. The genetic studies have shown the relationships of folate-related genes. Spina bifida aperta may be referred to as either myeloschisis or myelomeningocele. Myelomeningocele is when the spinal cord protrudes from the spinal canal into a fluid-filled sac resulting from incomplete closure of the primary neural tube. Myeloschisis is when the incomplete closure of the primary neural plate results in a cleft spinal cord with the edges flush with the defect. Myelomeningocele is usually associated with a type II Chiari hindbrain malformation, ventriculomegaly, and hydrocephalus.","Congenital malformation"
"H02151","Hereditary congenital facial paresis","Hereditary congenital facial paresis (HCFP) belongs to the congenital cranial dysinnervation disorders. HCFP is characterized by the dysfunction of the seventh cranial nerve and can be associated with hearing loss, strabismus, and orofacial anomalies. Genetic heterogeneity for this disorder has been suggested. The only known causative gene for HCFP is HOXB1.","Congenital malformation"
"H00606","Early infantile epileptic encephalopathy","Early infantile epileptic encephalopathy (EIEE) is characterized by frequent tonic spasms of early onset within a few months of life, and a suppression-burst pattern in electroencephalography (EEG). Many causes have been considered for EIEE. It has been reported that 75% of the cases subsequently evolve to West syndrome, and later a much smaller number progress to Lennox-Gastaut syndrome.","Nervous system diseases"
"H00434","Camurati-Engelmann disease","Camurati-Engelmann disease (CED) is an autosomal dominant disorder characterized by hyperostosis of the diaphysis of long bones and the skull. The onset of CED is during early childhood with muscle weakness and limb pain. The mutations in TGF-beta 1 LAP domain modulate TGF-beta 1 activity and leads to increased proliferation of osteoblasts in CED.","Congenital malformation"
"H02363","Ververi-Brady syndrome","Ververi-Brady syndrome (VERBRAS) is characterized by by mild developmental delay, mildly impaired intellectual development and speech delay, and mild dysmorphic facial features. It has been suggested that mutations in QRICH1 cause VERBRAS.","Congenital malformation"
"H01149","Ring dermoid of cornea","The ring dermoid of the cornea (RDC) is an autosomal dominantly inherited syndrome characterised by bilateral annular limbal dermoids with corneal and conjunctival extension. A mutation in PITX2 has been identified in the individuals affected by the RDC. PITX2 encodes a homeodomain transcription factor required for normal development of multiple organs, including eye, heart, and pituitary.","Nervous system disease"
"H01975","Welander distal myopathy","Welander distal myopathy (WDM) is an autosomal dominant disorder with late onset predominantly affecting distal extensor muscles of the hands and the feet. The disorder is considered as the most common of the distal myopathies but is almost only seen in Sweden and some parts of Finland. WDM is caused by mutations in TIA1 gene which encodes a key component of stress granules.","Nervous system disease; Musculoskeletal disease"
"H00639","Ectodermal dysplasia, ectrodactyly, and macular dystrophy","Ectodermal dysplasia with ectrodactyly and macular dystrophy (EEM syndrome) is the rare association of several clinical features caused by defects in CDH3. The ectodermal defect is characterized by hypotrichosis with sparse and short scalp hair, eyebrows, and eyelashes. Digit deficiency/syndactyly in hands is often more severe than the feet. Bilateral retinal degeneration appears as prominent pigmentation of the retina.","Congenital malformation"
"H01981","Carnitine palmitoyltransferase I deficiency","Carnitine palmitoyltransferase 1 (CPT1) deficiency is a rare autosomal recessive disorder of mitochondrial fatty acid oxidation. CPT1 controls the import of long-chain fatty acids into the mitochondria. Defects in the liver isoform of CPT1 (CPT1A) present with recurrent attacks of fasting hypoketotic hypoglycemia.","Inherited metabolic disease; Mitochondrial disease"
"H00853","Cenani-Lenz syndactyly syndrome","Cenani-Lenz syndactyly syndrome is an autosomal-recessive congenital malformation syndrome characterized by syndactyly and/or oligodactyly and kidney anomalies. The cause of Cenani-Lenz syndactyly syndrome is LRP4, a low-density lipoprotein receptor that modulates Wnt signaling.","Congenital malformation"
"H00433","Holt-Oram syndrome","Holt-Oram syndrome (HOS) is an autosomal-dominant disorder characterized by bilateral forelimb anomalies and congenital heart diseases. All patients with HOS have abnormal carpal bones and about 85% to 95% develop cardiac malformation including atrial septal defect and ventricular septal defect. The disease is caused by mutations of the T-box transcription factor TBX5.","Congenital malformation"
"H02364","Heart and brain malformation syndrome","Heart and brain malformation syndrome (HBMS) is a multiple congenital anomaly syndrome, characterized by craniofacial dysmorphism, congenital heart disease, and brain malformation. Mutations in SMG9, encoding an essential component of nonsense-mediated decay (NMD) machinery, cause this disease.","Congenital malformation"
"H02156","Lamb-Shaffer syndrome","Lamb-Shaffer syndrome is a neurodevelopmental disorder characterized by developmental delay, mild to moderate intellectual disability, speech delay, and mild characteristic facial appearance. It is caused by haploinsufficiency of SOX5 at 12p12.1. SOX5 encodes a transcription factor involved in the regulation of chondrogenesis and the development of the nervous system.","Chromosomal abnormality"
"H00601","Hutchinson-Gilford progeria syndrome","Hutchinson-Gilford progeria syndrome (HGPS) is a rare hereditary disorder characterized by premature aging. Children born with HGPS begin to develop micrognathia, alopecia, prominent scalp vein, and wrinkled, aged-looking skin within the first year of life. Severe premature atherosclerosis can cause the death at an average age of 13.5 years. Mutations in lamin A/C, an important structural component of the nuclear envelope, have been reported.","Congenital disorder of metabolism"
"H00265","Hereditary sensory and autonomic neuropathy","Hereditary sensory and autonomic neuropathies (HSAN) are a clinically and genetically heterogeneous group of disorders of low prevalence. They are characterized by neuronal atrophy and degeneration, predominantly affecting peripheral sensory and autonomic neurons. Hallmark features are progressive sensory loss, chronic skin ulcers, and other skin abnormalities. Autonomic features vary between different subgroups.","Nervous system disease"
"H01185","Cerebral amyloid angiopathy","Cerebral amyloid angiopathy (CAA) is characterized by the deposition of congophilic material in the vessels of the cortex and leptomeninges. Although CAA most commonly appears in a sporadic form associated with aging, several familial forms of CAA reported to date. Hereditary cystatin C amyloid angiopathy (HCCAA) is a rare, fatal amyloid disease in young people in Iceland caused by a mutation in cystatin C, which is an inhibitor of several cysteine proteinases. It has also been reported that mutations in APP are linked to CAA.","Neurodegenerative disease"
"H00057","Parkinson disease","Parkinson disease (PD) is a progressive neurodegenerative movement disorder that results primarily from the death of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). Both environmental factors and mutations in familial PD-linked genes such as SNCA, Parkin, DJ-1, PINK1 and LRRK2 are associated with PD pathogenesis. These pathogenic mutations and environmental factors are known to cause disease due to oxidative stress, intracellular Ca2+ homeostasis impairment, mitochondrial dysfunctions and altered protein handling compromising key roles of DA neuronal function and survival. The demise of DA neurons located in the SNc leads to a drop in the dopaminergic input to the striatum, which is hypothesized to impede movement by inducing hypo and hyper activity in striatal spiny projection neurons (SPNs) of the direct (dSPNs) and indirect (iSPNs) pathways in the basal ganglia, respectively.","Neurodegenerative disease"
"H01343","Pantoea ananatis infection","Pantoea ananatis, a gram-negative, motile rod belonging to the family Enterobacteriaceae, is known as an emerging phytopathogen infecting a wide range of important crop and forest plants, and has been reported as an occasional clinical isolate. It has been considered a presumptive and opportunistic human pathogen that associated with septicemia following penetrating trauma with plant material, nosocomial infections due to exposure to contaminated hospital materials, and secondary complications of preexisting illnesses.","Infectious disease"
"H00291","Familial chilblain lupus (FCL)","Familial chilblain lupus (FCL) is a rare, inherited form of cutaneous lupus with prominent skin manifestations in acral parts of the body. Two families with autosomal dominant-inherited chilblain lupus have been reported. First symptoms manifest in early childhood, developing hypergammaglobulinemia and rheumatoid factor antibody production. In FCL, missense mutations in TREX1 that decrease its exonuclease activity were described. The failure of DNA degradation can result in aberrant immune response.","Immune system disease"
"H01171","Poor drug metabolism","Many administered drugs are first activated by phase I drug-metabolizing enzymes, such as cytochrome P450 (CYP). There are some defective activity mutants due to CYP polymorphisms. In these cases, drugs are not metabolized, the high drug levels in blood are maintained, and toxic effects appear in the patients.","Inherited metabolic disease"
"H01515","Scarlet fever","Scarlet fever, also called scarlatina, is caused by Streptococcus pyogenes (GroupA Streptococcus, GAS). The important diagnostic signs of scarlet fever include fever, sore throat, rash and bright red tongue with a 'strawberry' appearance. Scarlet fever can affect people of all ages, but it is usually attacking children under 10.","Infectious disease"
"H02390","Autosomal recessive neuromyotonia and axonal neuropathy","Autosomal recessive neuromyotonia and axonal neuropathy (NMAN) is a syndrome characterized by myokymia, myotonia, muscular wasting and increased perspiration. It has been reported that loss-of-function mutations in HINT1 cause this disease. HINT1 ubiquitously expressed in mammalian tissues, and it is a tumor suppressor that participates in several apoptotic pathways.","Nervous system disease"
"H01727","Primary alveolar hypoventilation syndrome","Primary alveolar hypoventilation syndrome (PAHS) is a rare disorder which shows hypoxemia and hypercapnia without apparent associated pulmonary, neuromuscular, and central nervous diseases. PAHS is characterized by exacerbation of hypoxemia during sleep. Disorders of both automatic and chemical control of ventilation are considered as a cause of this syndrome. PAHS occuring during infancy is called congenital cenral alveolar hypoventilation syndrome (CCHS). Although the relationship between CCHS and adult onset PAHS is unclear, the familial occurrence of PAHS may suggest an underlying genetic mechanism. It has been represented that some adult onset PAHS may be a mild type of CCHS. Recently, noninvasive positive pressure ventilation (NIPPV) has become available for PAHS.","Respiratory disease"
"H00068","Leber hereditary optic atrophy","Leber hereditary optic neuropathy (LHON) is a maternally transmitted inherited genetic disease underlying mutation of mitochondrial DNA (mtDNA). It is primarily an ophthalmological disorder, presenting predominantly in young adult males and characterized by acute or subacute bilateral optic atrophy that results in the loss of central vision. In most of the patients with LHON, visual dysfunction is the only manifestation of the disease. The incidence of LHON in Western Europe is 1/30000-1/50000; at least 1 in 14000 males is affected.","Nervous system disease; Congenital disorder of metabolism"
"H01986","Legius syndrome","Legius syndrome (LS) is a mild neurofibromatosis type 1-like syndrome. Multiple cafe-au-lait spots and macrocephaly are present. LS is caused by germline loss-of-function SPRED1 mutations. SPRED1 is a negative regulator of the MAPK signalling cascade by suppressing Raf phosphorylation.","Congenital malformation"
"H00854","Wolfram syndrome","Wolfram syndrome (WFS) is a rare hereditary neurodegenerative disorder also known as DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). Two different categories of WFS (WFS1 and 2) are recognized, each with its own subset of variable symptoms, and resulting from mutations in the WFS1 and CISD2 genes, respectively. The WFS1 encodes an endoplasmic reticulum membrane-embedded protein. ERIS, the protein that CISD2 encodes, also localizes to the endoplasmic reticulum.","Endocrine and metabolic disease"
"H01388","Hyperprolactinemia","Hyperprolactinemia unrelated to pregnancy is a disorder characterized by excess production of prolactin (PRL) and may result in infertility, hypogonadism, and galactorrhea. Such nonphysiological hyperprolactinemia is caused mainly by drugs or by tumors in the anterior pituitary gland, which are usually identifiable by means of magnetic resonance imaging (MRI). Some cases are due to prolactinomas and lesions in the pituitary stalk. A human germline PRLR mutation has been found in familial isolated hyperprolactinemia.","Endocrine disease"
"H02169","Hennekam lymphangiectasia-lymphedema syndrome","Hennekam lymphangiectasia-lymphedema syndrome (HKLLS) is characterized by congenital lymphedema, lymphangiectasia, unusual facial morphology, and variable intellectual disabilities. Mutations in CCBE1, an extracellular matrix protein essential for the development of the lymphatic vasculature, have been found responsible for the syndrome. As a second cause for HKLLS, the mutations in FAT4 has been described.","Congenital malformation"
"H01718","Kawasaki disease","Kawasaki disease (KD) is an acute systemic vasculitis of childhood that does not have a known cause or aetiology. KD is a self-limited illness that is not associated with the production of autoantibodies or the deposition of immune complexes, and it rarely recurs. The disease is believed to result from an aberrant inflammatory response to an infectious trigger in a genetically predisposed individual. Classic (typical) Kawasaki disease is diagnosed based on the presence of a fever lasting five or more days, accompanied by four out of five findings: bilateral conjunctival injection, oral changes such as cracked and erythematous lips and strawberry tongue, cervical lymphadenopathy, extremity changes such as erythema or palm and sole desquamation, and polymorphous rash. Incomplete (atypical) Kawasaki disease occurs in persons with fever lasting five or more days and with two or three of these findings. The standard treatment of acute KD is intravenous immunoglobulin (IVIG) infusion and aspirin. However, 10-20% of patients show resistance to IVIG therapy and present higher risk of coronary vasculitis. If there is no response to treatment, patients are given a second dose of IVIG with or without corticosteroids or other adjunctive treatment.","Cardiovascular disease; Hematologic disease; Skin and connective tissue disease"
"H01972","Autoimmune polyendocrinopathy syndrome type 1","Autoimmune polyendocrine syndrome type 1 (APS1) is a multiorgan autoimmune disorder caused by mutations in AIRE, the autoimmune regulator gene. It is characterized by multiple autoimmune endocrinopathies, chronic mucocutaneous candidiasis, and ectodermal dystrophies. APS1 has been reported to be inherited in an autosomal recessive manner. However, a novel mutation was recently described to be inherited in a dominant fashion.","Primary immunodeficiency"
"H00253","Neurohypophyseal diabetes insipidus (NPDI)","Central Diabetes Insipidus is a heterogeneous condition characterized by polyuria and polydipsia caused by defect of antidiuretic hormone secreted from the pituitary gland.","Endocrine disease; Kidney disease"
"H01381","Antithrombin III deficiency","Inherited Antithrombin (AT) deficiency is an autosomal dominant disorder, that is associated with an increased risk for venous thromboembolism (VTE) and pregnancy loss. AT is a potent inactivator of thrombin and factor Xa and the major inhibitor of blood coagulation. This disease is divided into type I deficiency, in which both the functional activity and antigenic levels AT are proportionately reduced, and type II deficiency, in which normal antigen levels are found in association with low AT activity due to a dysfunctional protein. Type II deficiencies can be further subclassified into three types, depending on the location of the mutations. Type IIa is caused by mutations that affect AT's reactive site. Type IIb is characterized by an abnormality of the heparin-binding domain. Type IIc variants are a pleiotropic group of mutations near the reactive loop site.","Hematologic disease"
"H02504","Gastrointestinal ulceration, recurrent, with dysfunctional platelets","Gastrointestinal ulceration, recurrent, with dysfunctional platelets (GURDP) is an inherited cytosolic phospholipase A2 (cPLA2) deficiency due to mutations in PLA2G4A. Patients have severe peptic ulcers and bleeding beginning at an early age. cPLA2 catalyzes the hydrolysis of phospholipids to arachidonic acid and lysophospholipids that are precursors of numerous bioactive lipids.","Digestive system disease"
"H00061","Prion disease","Prion diseases, also termed transmissible spongiform encephalopathies (TSEs), are a group of fatal neurodegenerative diseases that affect humans and a number of other animal species. The etiology of these diseases is thought to be associated with the conversion of a normal protein, PrPC, into an infectious, pathogenic form, PrPSc. The conversion is induced by prion infections (for example, variant Creutzfeldt-Jakob disease (vCJD), iatrogenic CJD, Kuru), mutations (familial CJD, Gerstmann-Straussler-Scheinker syndrome, fatal familial insomnia (FFI)) or unknown factors (sporadic CJD (sCJD)), and is thought to occur after PrPC has reached the plasma membrane or is re-internalized for degradation. The PrPSc form shows greater protease resistance than PrPC and accumulates in affected individuals, often in the form of extracellular plaques. Pathways that may lead to neuronal death comprise oxidative stress, regulated activation of complement, ubiquitin-proteasome and endosomal-lysosomal systems, synaptic alterations and dendritic atrophy, corticosteroid response, and endoplasmic reticulum stress. In addition, the conformational transition could lead to the lost of a beneficial activity of the natively folded protein, PrPC.","Neurodegenerative disease"
"H02352","Vaccinia","Vaccinia is an infectious disease caused by vaccinia virus, an orthopoxvirus in the Poxviridae family of dsDNA viruses. Vaccinia virus has been used as a smallpox vaccine. Several serious complications such as encephalitis, progressive vaccinia, eczema vaccinatum, and generalized vaccinia and disseminated vaccinia have been reported.","Infectious disease"
"H00405","Marburg disease","Marburg disease is a severe infectious disease caused by marburgviruses within the genus Marburgvirus in the family Filoviridae of -ssRNA viruses. Related viruses in Filoviridae are the causative agent of Ebola hemorrhagic fever. Marburgvirus was discovered in 1967 in Germany.","Infectious disease"
"H00637","Ulnar-mammary syndrome","Ulnar-mammary syndrome (UMS) is an autosomal dominant disorder caused by haploinsufficiency of the TBX3 gene. It is characterized by bilateral hypoplasia or aplasia of upper limbs on the ulnar side, mammary and apocrine gland hypoplasia, and genital abnormalities. Delayed puberty is one of the recognized features in UMS.","Congenital malformation"
"H02160","Craniosynostoses","Craniosynostosis (CRS) is the premature fusion of the cranial sutures and secondary distortion of skull shape.","Congenital malformation"
"H01523","Wiskott-Aldrich syndrome","The Wiskott-Aldrich syndrome (WAS) is a rare X-linked recessive immunodeficiency disorder, caused by mutations in the Wiskott-Aldrich syndrome protein (WASP) gene, and characterised by thrombocytopenia, small platelets, eczema, and recurrent infections associated with increased risk of autoimmunity and malignancy disorders. Recent research suggested that the WIPF1-encoded protein WIP binds to the region of WASP which is frequently mutated in patients with this disease, and WIP mutations themselves lead to an immunological disorder resembling Wiskott-Aldrich syndrome.","Primary immunodeficiency"
"H01711","Spinal stenosis","Spinal stenosis is an abnormal narrowing of the spinal canal that mainly occurs in the cervical and lumbar regions. Cervical stenosis presents with axial neck pain, radiculopathy, myelopathy, or a combination of these presentations. Axial pain refers to pain that occurs along the spinal column, while radiculopathy refers to complaints in a dermatomal or myotomal distribution often occurring in the arms. Patients may complain of numbness, pain or loss of function. Myelopathy refers to a cluster of complaints and findings due to intrinsic damage to the spinal cord itself. Patients might report numbness, coordination and gait issues, grip weakness and bowel and bladder complaint. Lumbar spinal stenosis is a major cause of pain and functional disability for the elderly. Neurogenic claudication symptoms are a hallmark of lumbar spinal stenosis, where patients develop low back or leg pain when walking or standing that is relieved by sitting or lumbar flexion. The treatment of lumbar spinal stenosis generally begins with conservative management such as physical therapy, home exercise programs, and oral analgesics. Once these therapies fail, patients commonly move forward with interventional pain treatment options such as epidural steroid injections (ESIs), nerve block, or surgery as the next step. Coexisting lumbar and cervical stenosis (tandem spinal stenosis) is an infrequent presentation with mixed presentation of upper motor neuron and lower motor neuron signs. But very few reports of tandem spinal stenosis are available.","Musculoskeletal disease"
"H02194","North American Indian childhood cirrhosis","North American Indian childhood cirrhosis (NAIC) is a severe autosomal-recessive intrahepatic cholestasis found in aboriginal children from northwestern Quebec. It typically presents with transient neonatal jaundice, in a child who is otherwise healthy, and progresses to biliary cirrhosis and portal hypertension. It has reported that a missense mutation in Cirhin causes NAIC. Cirhin/UTP4 is known to be required for ribosome biogenesis.","Digestive system disease"
"H01375","Glucose 6-phosphate dehydrogenase deficiency","Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked, hereditary disorder due to mutations in the G6PD gene, resulting in protein variants with different levels of enzyme activity, that are associated with a wide range of biochemical and clinical phenotypes. G6PD deficiency is the most common enzymatic disorder in humans. It is estimated that about 400 million people are affected by this deficiency. More than 400 biochemical variants of G6PD deficiency have since been defined, and grouped into five classes based on enzyme activity and clinical manifestations. The most common clinical manifestations are neonatal jaundice and acute haemolytic anaemia, which in most patients is triggered by an exogenous agent. A G6PD-deficient patient lacks the ability to protect red blood cells against oxidative stresses from certain drugs, infections, metabolic conditions, and ingestion of fava beans.","Inherited metabolic disease; Hematologic disease"
"H00095","Ectodermal dysplasia associated immunodeficiency","Ectodermal dysplasia (ED) refers to a group of inherited disorders involving absence or dysplasia of the ectodermal appendages. Clinically, it is characterized by absence, abnormality, or deficient function of ectodermal derivatives, including skin, teeth, hair, eccrine glands, or nails. In the hypohidrotic/ anhidrotic form of ED (HED/EDA) the patient has no sweat glands, sparse scalp hair and rare conical teeth. Patients with EDA and immunodeficiency (EDA-ID) present some or all of these features, together with severe infectious diseases. EDA-ID principally affects boys, suggesting X-linked recessive inheritance (XL-EDA-ID). This was confirmed in 2000 and beyond with the identification of disease-causing hypomorphic mutations in NEMO, which is located on the X chromosome and encodes IKK-gamma. A novel autosomal dominant of EDA-ID, recently identified in one child, was found to be caused by a hypermorphic mutation of the gene encoding I{kappa}B{alpha}. Similar to XL-EDA-ID patients, from the age of two months he suffered from multiple and severe infections with several Gram-positive and Gram-negative bacteria, leading to chronic bronchopneumonitis and gastroenteritis, with failure to thrive.","Immune system disease"
"H01147","Methylobacterium infection","Methylobacterium species are fastidious, pink-pigmented, gram-negative bacilli that rarely cause human infections. It has been reported to that the bacterium can cause catheter-related infection in both immunocompromised and immunocompetent patients.","Infectious disease"
"H00608","46,XY disorder of sex development due to testosterone secretion defect","46,XY disorders of sex development (46,XY DSD) are characterized by ambiguous or female external genitalia, caused by incomplete intrauterine masculinization, and the presence or absence of Mullerian structures. Several enzymatic defects that result in insufficient production of testosterone have been reported. And impaired differentiation of Leydig cell, which secretes testosterone, can lead to 46,XY DSD.","Reproductive system disease"
"H00862","Tourette syndrome","Tourette's syndrome (TS) is a developmental neuropsychiatric disorder characterized by chronic motor and vocal tics. Rare functional variants in the neuronal transmembrane molecule SLITRK1 have been associated with TS. The SLITRK1 gene is expressed in brain regions and it appears to play a role in dendritic growth. Another possible rare genetic cause of TS is a mutation in the HDC gene. The HDC gene encodes for L-histidine decarboxylase, which is the rate-limiting enzyme that catalyzes the biosynthesis of histamine from histidine.","Mental and behavioural disorder"
"H01178","Myiasis","Myiasis is a parasitic infestation of vital tissue of the skin and mucous membranes by dipterous larvae. Human myiasis is a rare clinic condition but more prevalent in humid tropical and subtropical regions. Myiasis may be classified into three types: (i) primary myiasis in which the larva invades healthy tissue of the host, (ii) secondary myiasis where the adult female is attracted to and lays its eggs on wounded skin, and (iii) accidental myiasis caused by ingestion of contaminated food. Among many species of Diptera that cause larval infection in humans, Dermatobia hominis, the human botfly, is responsible for the painful, boil-like lesion of furuncular myiasis.","Infectious disease"
"H00896","Lymphangioleiomyomatosis","Lymphangioleiomyomatosis (LAM) is a rare lung disease, primarily affecting women. Abnormal proliferation of smooth muscle-like cells (LAM cells) within the lung is responsible for cystic destruction of the lung parenchyma and leads to chronic respiratory failure. Another characteristic feature of the disease is the development of fluid-filled lymphatic cystic structures (lymphangioleiomyomas) in the axial lymphatics and of angiomyolipomas in the kidneys. Its presentation is sporadic or associated with tuberous sclerosis complex, a dominant autosomal neurocutaneous syndrome. Both disorders have their origin in mutations of the tuberous sclerosis genes TSC1 and TSC2, which are involved in the regulation of cell signs critical for energy control and cell nutrition processes.","Cancer; Cardiovascular disease; Immune system disease"
"H01944","Glycogen storage disease type VI","Glycogen storage disease type VI (GSD-VI), also known as Hers disease, is an autosomal recessive disorder of glycogen metabolism. GSD-VI is caused by mutations in the PYGL gene, which encodes liver glycogen phosphorylase. It manifests in infants, primarily with hepatomegaly and growth retardation.","Inherited metabolic disease"
"H00298","Yersiniosis","Yersiniosis (non-plague) is an infectious disease caused by two species, Yersinia enterocolitica and Y. pseudotuberculosis, which is zoonotic, capable of being transmitted from infected animals to man. Routes of transmission include fecal-oral spread via ingestion of contaminated food as the most common route and consumption of contaminated water supplies. Yersiniosis occurs more commonly in regions with temperate rather than tropical or subtropical climates.","Infectious disease"
"H02399","Primary amoebic meningoencephalitis (PAM)","Primary amoebic meningoencephalitis (PAM) is a perilous and devastating waterborne disease caused by Naegleria fowleri. N. fowleri is a free-living, thermophilic amoeba distributed worldwide in soil and warm freshwater. PAM is a rare but fatal disease usually affecting children and young adults all around the world. This acute infection is developed by the entry of N. fowleri through nasal cavity.","Infectious disease"
"H00092","T-B-Severe combined immunodeficiency","Severe combined immunodeficiency (SCID) comprises a heterogeneous group of monogenic disorders that result in early-onset severe infections by a range of pathogens (such as bacteria, viruses and fungi). Typically, patients with SCID have a severe defect in T-cell differentiation, along with direct or indirect impairment of B-cell development and function. Adenosine deaminase (ADA) deficiency accounts for about half of the autosomal recessive forms of SCIDs. It is one of the most severe immunodeficiencies and is associated with severe depletion of B cells, T cells, and NK cells. V(D)J- recombination deficiency caused by defects in recombinase-activating gene 1 (RAG1), RAG2 and Artemis (DCLRE1C) leads to a T-B-SCID phenotype that is characterized by an arrest of B- and T-cell maturation at the stage of pro-B and pre-T cells, respectively, whereas natural killer (NK)-cell maturation is not affected. V(D)J recombination generates the diversity of B- and T-cell primary immune repertoires.","Primary immunodeficiency"
"H01140","Sennetsu neorickettsiosis","Neorickettsia sennetsu, an obligate intracellular bacteria closely related to Ehrlichia and Anaplasma, causes an infectious mononucleosis-like disease. It is very likely linked to consumption of raw fish in tropical Asia. Patients with sennetsu neorickettsiosis experience acute febrile disease, malaise, myalgias, pharyngitis, anorexia, generalized lymphadenopathy, and peripheral blood mononucleosis.","Infectious disease"
"H01372","Vitiligo","Vitiligo is a common, multifactorial, polygenic disease in which autoimmune loss of melanocytes results in depigmented spots of skin, overlying hair, and mucous membranes. Some familial forms of vitiligo have recently been linked to polymorphisms in the innate immunity gene, NLRP1.","Skin and connective tissue disease"
"H01716","Idiopathic interstitial pneumonias","Idiopathic interstitial pneumonias (IIP) are a heterogeneous subset of interstitial lung diseases, characterized by unknown aetiology. Despite the varied nature of IIPs, the common histological feature is distortion of lung interstitium by highly variable combinations of inflammation and fibrosis. Patients experience common symptoms related to their chronic lung disease. Dyspnoea, cough, fatigue and depression contribute substantially to morbidity and are often difficult to manage. It has been reported that pulmonary rehabilitation plays a central role in symptom management and has beneficial effects. According to the current American thoracic society/European respiratory society (ATS/ERS), IIPs are categorised as major IIPs, rare IIPs and unclassifiable IIPs. There are six major IIPs, namely, idiopathic pulmonary fibrosis (IPF), nonspecific interstitial pneumonia (NSIP), respiratory bronchiolitis-interstitial lung disease (RB-ILD), desquamative interstitial pneumonia (DIP), cryptogenic organizing pneumonia (COP), and acute interstitial pneumonia (AIP). And they are divided into three major groups; chronic fibrosing IIP (IPF, NSIP), smoking-related IIP (RB-ILD, DIP), and acute/ subacute IIP (COP, AIP). The rare IIPs include idiopathic lymphoid interstitial pneumonia (LIP) and idiopathic pleuroparenchymal fibroelastosis. IPF accounts for the majority of IIP. It is considered to be lethal because prognosis is very poor and far worse than other types of IIP. An early and accurate diagnosis of IPF is critical.","Lung disease"
"H02193","Intrahepatic cholestasis of pregnancy","Intrahepatic cholestasis of pregnancy (ICP), also called obstetric cholestasis, is the most common pregnancy-specific liver disease. Classic symptoms include generalized pruritus that commonly includes the palms and soles, and biochemical evidence of elevated bile acids, with or without elevated liver function tests (LFTs). The etiology of ICP is influenced by a combination of genetic, endocrine, and environmental factors. Risk factors for ICP include multiple pregnancy, in vitro fertilization, advanced maternal age, history of prior affected pregnancy, positive family history, and hepatitis C infection.","Digestive system disease"
"H01524","DiGeorge syndrome","DiGeorge syndrome (DGS) is a primary immunodeficiency disease characterized by dysgenesis of the thymus and parathyroid glands, conotruncal cardiac anomalies, and other dysmorphic features. This syndrome is usually associated with hypocalcemia resulting from hypoparathyroidism. In most cases the initial symptom is tetany caused by hypocalcemia within 24-48 hours after birth, with symptoms by immune abnormality appearing later. Most patients with this syndrome have a genomic deletion of chromosome 22q11, including the DiGeorge critical region (DGCR). A small number of cases of DGS have defects in other chromosomes, notably 10p13. Approximately 17% of patients with the phenotypic features of this syndrome have no detectable genomic deletion. Several mutations in TBX1 have been identified recently in non-deleted patients, including missense and frameshift mutations.","Primary immunodeficiency; Developmental disorder"
"H00630","Rheumatoid arthritis","Rheumatoid arthritis (RA) is a common autoimmune disease that primarily manifests as chronic inflammatory arthropathy. Persistent synovitis leads to cartilage destruction, bone erosions and periarticular decalcification, subsequently resulting in impaired joint function. It is more common between the ages of 35 and 50 years, affecting three times more women than men. Susceptibility to RA is genetically determined with multiple genes contributing. Inheritance of HLA DRB1 alleles encoding a distinctive five-amino-acid sequence known as the 'shared epitope' (SE) is the best characterized genetic risk factor. The mechanism by which the SE alleles contribute to the development of RA is not very clear. It has been postulated that the presence of these conserved sequences in the antigen-binding groove alters the way antigenic peptides are bound to and presented to T-cell lymphocytes. This, in turn, may trigger abnormal immune responses and lead to RA.","Autoimmune disease"
"H02167","Lymphedema-distichiasis syndrome","Lymphedema-distichiasis syndrome (LD) is an autosomal dominant disorder, characterized by late childhood or pubertal onset lymphedema of the limbs and double row of eyelashes. LD has been reported to be caused by mutations in the forkhead transcription factor, FOXC2.","Congenital malformation"
"H02355","Deafness and myopia","Deafness and myopia (DFNMYP) is severe congenital myopia and sensorineural hearing loss in the absence of other systemic, ocular, or connective tissue manifestations. DFNMYP is caused by mutations in SLITRK6. SLITRK family proteins control neurite outgrowth and regulate synaptic development.","Nervous system disease"
"H00402","Severe acute respiratory syndrome","Severe acute respiratory syndrome (SARS) is a viral respiratory illness caused by SARS coronavirus. SARS first emerged in 2002 and gained global from 2002 to 2003. The main mode of transmission of SARS coronavirus is person-to-person spread through inhalation of respiratory droplets.","Infectious disease"
"H00066","Lewy body dementia (LBD)","Lewy Body dementia (LDB) is neurodegenerative disease characterized by dementia, mild parkinsonism, and fluctuations in attention and alertness. It is the second most-common degenerative dementia after Alzheimer's disease. Progressive accumulation of alpha-synuclein- and ubiquitin-positive Lewy Bodies is seen in the brainstem, the limbic system or cortical and subcortical regions, depending on disease subtype. The genetic risk factors include alpha-synuclein mutations and SNCA locus triplicationslocus triplications. Mutations of leucine-rich repeat kinase 2 (LRRK2) and the glucocerebrosidase (GBA) gene have also been implicated in familial DLB.","Neurodegenerative disease"
"H01988","Jackson-Weiss syndrome","Jackson-Weiss syndrome (JWS) is an autosomal dominant condition characterized by craniosynostosis, foot anomalies and great phenotypic variability. While mutations of multiple genes have been identified in syndromic craniosynostosis, the most frequently mutated gene is FGFR2. Mutations of FGFR1 have occasionally been identified in JWS.","Congenital malformation"
"H00254","Growth hormone deficiency","Growth hormone deficiency, formerly known as Pituitary dwarfism, is a heterogeneous condition characterized by growth retardation with short statue and normal body proportions caused by growth hormone deficiency.","Endocrine and metabolic disease"
"H01386","Asparagine synthetase deficiency","Asparagine synthetase deficiency is an autosomal recessive disorder characterized by congenital microcephaly, intellectual disability, progressive cerebral atrophy, and intractable seizures. Recessive mutations in the ASNS gene, encoding asparagine synthetase which catalyzes the synthesis of asparagine from glutamine and aspartate, are responsible for this syndrome.","Inherited metabolic disease; Nervous system disease"
"H02503","Richieri-Costa-Pereira syndrome","Richieri-Costa-Pereira syndrome (RCPS) is a rare autosomal recessive disorder characterized by short stature, Robin sequence, cleft mandible, and limb anomalies. This disorder is caused by decreased levels of EIF4A3, mostly due to an increased number of repeats at the 5'untranslated region (UTR) of EIF4A3.","Congenital malformation"
"H01729","Premature ventricular complexes","Premature ventricular complex (PVC) is characterized by the premature occurrence of a QRS complex that is bizarre in shape and lasts longer than 120 msec. The T wave is large and usually of opposite polarity to the QRS complex. A PVC is usually followed by a full compensatory pause. PVCs are commonly encountered in apparently healthy individuals with a reported incidence of approximately 1% on standard 12-lead electrocardiograms (ECG) and 40% to 75% on routine 24 hour to 48 hour Holter monitoring. The clinical presentation may range from asymptomatic to left ventricular (LV) dysfunction with congestive heart failure. In many patients, ectopic ventricular events manifest as asymptomatic, isolated PVCs that have a benign prognosis in those without structural heart disease. In others, PVCs may be frequent and highly symptomatic, presenting as palpitations, chest discomfort, or presyncope. Clinical evidence suggests that frequent PVCs (variably defined in the literature) are more strongly associated with concomitant cardiac disease. The decision to suppress PVCs is largely based on the presence of symptoms, interference with other therapy (e.g., cardiac resynchronization therapy), or suspicion of PVC-mediated cardiomyopathy. When necessary, treatment for PVCs involves beta-blockers, calcium channel blockers, or other antiarrhythmic drugs and catheter ablation in selected cases. Catheter ablation of frequent PVCs has been demonstrated to be effective at PVC suppression and is associated with improvement or normalization of ventricular function.","Cardiovascular disease"
"H00891","Combined oxidative phosphorylation deficiency","Combined oxidative phosphorylation deficiency (COXPD) is a group of multisystem disorders with variable manifestations resulting from a defect in the mitochondrial oxidative phosphorylation system. It has been reported that the mutations in the ribosomal protein gene (MRPS) cause severe antenatal-onset infantile disease. The patients with COXPD caused by mutations in mitochondrial translation elongation factor genes (GFM1, GFM2, TUFM, TSFM and C12orf65) have also been reported.","Inherited metabolic disease; Mitochondrial disease"
"H01943","Glycogen storage disease type V","Glycogen storage disease type V (GSD-V), also known as McArdle disease, is an autosomal recessive disorder of glycogen metabolism. GSD-V is caused by mutations in the PYGM gene, which encodes muscle glycogen phosphorylase. It is characterized by exercise intolerance, muscle cramping, and myoglobinuria.","Inherited metabolic disease"
"H00059","Huntington disease","Huntington disease (HD) is an autosomal-dominant neurodegenerative disorder that primarily affects medium spiny striatal neurons (MSN). The symptoms are choreiform, involuntary movements, personality changes and dementia. HD is caused by a CAG repeat expansion in the IT15 gene, which results in a long stretch of polyglutamine (polyQ) close to the amino-terminus of the HD protein huntingtin (Htt). Mutant Htt (mHtt) has effects both in the cytoplasm and in the nucleus. Full-length Htt is cleaved by proteases in the cytoplasm, leading to the formation of cytoplasmic and neuritic aggregates. mHtt also alters vesicular transport and recycling, causes cytosolic and mitochondrial Ca2+  overload, triggers endoplasmic reticulum stress through proteasomal dysfunction, and impairs autophagy function, increasing neuronal death susceptibility. N-terminal fragments containing the polyQ strech translocate to the nucleus where they impair transcription and induce neuronal death.","Neurodegenerative disease"
"H00865","Lethal congenital contractural syndrome","Lethal congenital contractural syndrome (LCCS) is a heterogeneous group of disorders characterized by congenital nonprogressive joint contractures with a severe form of arthrogryposis. LCCS is inherited in an autosomal recessive manner. It has a worldwide incidence, but it is more common in isolated populations, such as Finland and the Bedouin community in Israel. Several mutations associated with LCCS have been reported.","Congenital malformation"
"H02158","Weyers acrofacial dysostosis","Weyers acrofacial dysostosis, also known as Curry-Hall syndrome, is an autosomal dominant condition with dental anomalies, nail dystrophy, postaxial polydactyly, and mild short stature. It is caused by mutations in EVC1 or EVC2 genes. Both EVC1 and EVC2 localize to the basal bodies of primary cilia and play a role in hedgehog signaling.","Congenital malformation"
"H01917","CK syndrome","CK syndrome (CKS) is a recently described X-linked recessive disorder that affects males. It is characterized by mild to severe cognitive impairment, seizures beginning in infancy, microcephaly, cerebral cortical malformations, and a thin body habitus. Distinctive features include down slanting palpebral fissures, a high nasal bridge, a high arched palate, micrognathia, and short stature. Patients also have behavior problems, including aggression, attention deficit hyperactivity disorder, and irritability. Some have scoliosis and kyphosis. CK syndrome is caused by mutations in NSDHL, a gene that encodes an enzyme in the cholesterol biosynthesis pathway.","Congenital malformation"
"H01319","Coccidioidomycosis","Coccidioides immitis and C. posadasii are two endemic dimorphic fungal pathogens that cause coccidioidomycosis, also called ballet fever, and are found in the southwestern United States and northern Mexico. Pulmonary symptoms are the most common features. Nearly all cases of coccidioidal pneumonia are self-limited. Infection is caused by inhalation of spores that aerosolizes from disruptions of the soil.","Infectious disease"
"H00831","Primary dystonia","Dystonias are a heterogeneous group of hyperkinetic movement disorders characterized by involuntary sustained muscle contractions that lead to abnormal postures and repetitive movements. Presently, 20 distinct monogenic primary dystonias have been recognized. They can be divided into Primary torsin dystonias (PTDs), dystonia-plus syndromes without brain degeneration, dystonia-parkinsonism with brain degeneration (i.e. DYT3), and paroxysmal dyskinesias.","Nervous system disease"
"H01789","You-Hoover-Fong syndrome","You-Hoover-Fong syndrome is an autosomal-recessive syndromic form of intellectual disability. It has been reported that compound heterozygous variants in TELO2 were found from six affected individuals from four families with intellectual disability and neurological and other congenital abnormalities, suggesting that these TELO2 variants result in loss of function and cause this disease.","Congenital malformation"
"H00469","Mitochondrial DNA depletion syndrome","Mitochondrial DNA depletion syndromes (MDSs) are a group of heterogeneous autosomal recessive disorders associated with a severe reduction in mitochondrial DNA in the affected tissues. The manifestations vary from tissue-specific mtDNA depletion to wide-spread multisystemic disorders. Some genes are known to underlie this group of disorders, and many disease genes are still unidentified. However, the disease mechanisms seem to be intimately associated with mtDNA replication and nucleotide pool regulation.","Inherited metabolic disease; Mitochondrial disease"
"H01326","Hand, foot and mouth disease","Hand, foot and mouth disease (HFMD) is a common infection among infants and young children caused by certain enteroviruses in the Picornaviridae family of +ssRNA viruses, such as Coxsackievirus A16 and Enterovirus A71. HFMD is generally a benign febrile exanthematous disease, but complications can occur causing meningitis and encephalitis.","Infectious disease"
"H01928","Smith-Kingsmore syndrome","Smith-Kingsmore syndrome (SKS), also known as macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome (MINDS syndrome), is a rare autosomal dominant disorder. Heterozygous mutations in MTOR gene have been shown to underlie SKS. The most consistent findings in SKS are intellectual disability (ID), developmental delay, megalencephaly, and seizures. There is moderate clinical variability, ranging from patients with macrocephaly, mild ID, and no convulsions, to severe forms in patients with intractable epilepsy, megalencephaly, severe ID, and autistic spectrum disorder.","Congenital malformation"
"H01114","Ocular coloboma","Ocular coloboma is a congenital and common malformation which includes a deficiency of the structures of the eye, such as the iris, retina, choroid, or optic disc. It is usually inherited as an autosomal dominant disorder, although autosomal recessive inheritance also occurs. Paired box gene 6 (PAX6), a member of the paired box family of transcription factors, has been identified as a key regulator of eye development. Currently around 500 mutations of PAX6 have been reported. And most PAX6 nonsense mutations lead to aniridia, while missense mutations are related to foveal hypoplasia, congenital cataracts, or anterior segment anomalies. Recently, it has been reported that mutation of SALL2 causes recessive ocular coloboma.","Congenital malformation"
"H01570","Autosomal dominant striatal degeneration","Autosomal-dominant striatal degeneration (ADSD) is a rare autosomal-dominant movement disorder affecting the striatal part of the basal ganglia, with onset in the fourth to fifth decade. The main clinical features are mild, slowly progressive dysarthria and hypokinesia without any apparent reduction in life expectancy. Brain MRI shows distinctive lesions of the putamen and caudate nucleus appearing earlier than the onset of symptoms. Causal gene mutations are discovered in the cyclic nucleotide phosphodiesterase (PDE) genes.","Nervous system disease"
"H01742","Coronary artery disease","Coronary artery disease (CAD) is one of the leading causes of death globally. CAD is coupled to a pathogenic process in which lipids and lipoproteins accumulate in the subendothelial intimal layer of the vessel wall. A variety of environmental and genetic risk factors are associated with CAD, including hypercholesterolemia, hypertension, obesity, diabetes, and a family history of early CAD. It has been reported that an autosomal dominant form of CAD is caused by the mutation in transcription factor MEF2A. A missense mutation in LRP6, which encodes a co-receptor in the Wnt signaling pathway, has also been identified.","Vascular disease"
"H00690","Aland Island eye disease","Aland Island eye disease (AIED) is an X-linked form of ocular hypopigmentation. Affected males demonstrate nystagmus, decreased visual acuity, myopia, astigmatism, achromatopsia, and fundus hypopigmentation.","Nervous system disease"
"H01584","IgA vasculitis","IgA vasculitis (IgAV), also known as Henoch-Schonlein purpura (HSP), is the most common systemic small vessel vasculitis in childhood with clinical characteristics of non-thrombocytopenic palpable purpura, arthritis, and involvement of internal organs such as gastrointestine (GI) and kidney. IgAV has been associated with a history of preceding infections, especially upper respiratory tract infection. In addition, other characteristics of IgAV include the deposition of IgA and C3 in small vessel walls, polymorphonuclear neutrophil infiltration around the vessel and in vessel walls, and increased serum levels of IgA and proinflammatory cytokines at the acute stage. Combined, IgAV is regarded as a specific immune-mediated entity induced by environmental factors, particularly infections. Clinically, since there are no disease-specific laboratory abnormalities, IgAV is currently diagnosed based on symptoms and signs and histopathological findings. Treatment is supportive because IgAV is usually self-limiting except for serious GI or renal involvement.","Cardiovascular disease"
"H00456","Fronto-otopalatodigital syndromes","Fronto-Otopalatodigital Osteodysplasia comprises four disorders that arise from missense mutations in FLNA encoding the actin-binding cytoskeletal protein filamin A. The disorders are inherited in X-linked fashion and characterized by a typical facial appearance and generalized osteodysplasia.","Congenital malformation"
"H02301","Nephroblastoma","Nephroblastoma, also called Wilms tumor (WT), is the most common renal tumor of childhood. It can present as a single nodule, as multifocal unilateral lesions or as bilateral tumours. Typically, nephroblastoma comprises three histological components namely blastemal, epithelial and stromal. WT1, a zinc-finger transcription factor, was identified as the first nephroblastoma gene. Several other genes including CTNNB1, WTX, and TP53 have also been implicated in various stages of tumorigenesis of nephroblastoma.","Cancer"
"H02133","Vici syndrome","Vici syndrome is a rare relentlessly progressive congenital multisystem disorder characterised by five principal features of callosal agenesis, cataracts, cardiomyopathy, combined immunodeficiency, and oculocutaneous hypopigmentation. Profound developmental delay, progressive failure to thrive, and acquired microcephaly are almost universal, suggesting an evolving (neuro) degenerative component. In most patients there is additional variable multisystem involvement that may affect virtually any organ system, including lungs, thyroid, liver, and kidneys. A skeletal myopathy is consistently associated. Recent studies identified mutations in the gene EPG5 as the cause of Vici syndrome. EPG5 is involved in autophagy, an evolutionarily conserved lysosomal degradation process that is essential for cell homeostasis.","Immune system disease"
"H00664","Anemia due to disorders of glycolytic enzymes","Anemia due to disorders of glycolytic enzymes is a group of red cell disorders caused by inherited abnormality of glycolytic enzymes. Neurological phenotypes have been found to be associated only with specific mutations affecting TPI, PGK and, in rare cases, GPI. The symptoms of TPI deficiency are generally much more severe than those of any other glycolytic enzyme deficiency.","Hematologic disease"
"H00200","Beta-ureidopropionase deficiency","Deficiency of beta-ureidopropionase which catalyzes the biosynthesis of beta-alanine and the last step in pyrimidine degradation is an autosomal recessive condition associated with neurological and developmental problems.","Inherited metabolic disease; Nervous system disease"
"H00032","Thyroid cancer","Thyroid cancer is the most common endocrine malignancy and accounts for the majority of endocrine cancer- related deaths each year. More than 95% of thyroid carcinomas are derived from follicular cells. Their behavior varies from the indolent growing, well-differentiated papillary and follicular carcinomas (PTC and FTC, respectively) to the extremely aggressive undifferentiated carcinoma (UC). Somatic rearrangements of RET and TRK are almost exclusively found in PTC and may be found in early stages. The most distinctive molecular features of FTC are the prominence of aneuploidy and the high prevalence of RAS mutations and PAX8-PPAR{gamma} rearrangements. p53 seems to play a crucial role in the dedifferentiation process of thyroid carcinoma.","Cancer"
"H02339","Auditory neuropathy","Auditory neuropathy is a rare form of deafness characterized by an absent or abnormal auditory brainstem response with preservation of outer hair cell function. DIAPH3 has been identified as the gene responsible for autosomal dominant nonsyndromic auditory neuropathy. Recently, it has been reported that an autosomal recessive auditory neuropathy and optic atrophy (ANOA) is caused by mutations in the FDXR gene.","Nervous system disease"
"H00238","Fanconi anemia","Fanconi anemia (FA), a recessive syndrome with both autosomal and X-linked inheritance, features diverse clinical symptoms, such as progressive bone marrow failures, chromosomal instability and susceptibility to cancer. To date, 13 FA gene products have been identified, which cooperate in a common DNA damage-activated signaling pathway regulating DNA repair (the FA pathway).","Hematologic disease"
"H00836","GLUT1 deficiency syndrome","GLUT1 deficiency syndrome (GLUT1DS) is an autosomal dominant or recessive inborn error of glucose transport across the blood-brain barrier. The majority of patients carry mutations in the SLC2A1 gene encoding the GLUT1 transporter. Defects in the GLUT1 result in low cerebrospinal fluid (CSF) glucose levels termed hypoglycorrhachia. Affected individuals present with mental retardation and learning disabilities; also common are ataxia, dystonia, seizures, and acquired microcephaly.","Nervous system disease"
"H01910","Infantile myofibromatosis","Infantile myofibromatosis (IM) is a benign fibrous tumour of infancy. The most common mode of presentation is with multiple subcutaneous swellings. Most IM lesions occur in neonates or infants under 24 months of age, with few reports of adult onset. It can occur in three forms: solitary, multicentric or generalised. The solitary form is the commonest and occurs as a single cutaneous nodule. The multicentric form involves the skin, subcutaneous tissues, muscles, and bone. The course is generally benign, with no metastases and regression of the tumor over a period of 12 to 18 months. The generalized form is associated with visceral involvement. This condition has serious prognostic implications as there is a 76% mortality from cardiopulmonary or gastrointestinal complications. While most cases of IM appear to be sporadic, there have been several reports of autosomal dominant inheritance pattern. Mutations in the PDGFRB and NOTCH3 genes were recently identified in patients with IM. Treatment options vary widely. Solitary and even multicentric lesions that are confined to the skin and subcutaneous tissues without visceral involvement frequently regress spontaneously. However, calcification and atrophic scars can remain after lesion regression. Extensive surgery has been reported to be beneficial for multicentric disease, as has chemotherapy.","Skin and connective tissue disease; Cancer"
"H01548","West Nile fever","West Nile fever is an infectious disease caused by West Nile virus (WNV), a flavivirus in the Flaviviridae family of +ssRNA viruses, and transmitted by Culex mosquitoes. WNV was first isolated in 1937 in Uganda.","Infectious disease"
"H00809","Familial epilepsy temporal lobe (ETL)","Autosomal dominant lateral temporal epilepsy (ADLTE) or autosomal dominant partial epilepsy with auditory features (ADPEAF) is an inherited epilepsy syndrome characterized by onset in adolescence or early adulthood of lateral temporal seizures with predominant auditory symptoms originating from the lateral temporal lobe cortex. Mutations in the leucine-rich glioma-inactivated 1 (LGI1) gene have been reported in up to 50% of ADTLE/ADPEAF pedigrees. In addition, de novo LGI1 mutations are found in about 2% of sporadic cases with idiopathic partial epilepsy with auditory features, who are clinically similar to the majority of patients with ADLTE/ADPEAF but have no family history.","Nervous system disease"
"H00035","Ewing sarcoma","Ewing sarcoma is the second most common malignant bone tumor occurring in children and young adults, and accounts for 10-15% of all primary bone tumors. The annual incidence is approximately 0.6/million total population, and it usually occurs between the ages of 10 and 20 years. Ewing's sarcoma is in 85% of cases associated with the translocation t(11;22)(q24;q12), which leads to the formation of the EWSR1-FLI1 fusion gene. In another 10-15% of cases the translocation t(21;12)(22;12) generates the EWSR1-ERG fusion, whereas the remaining 1-5% of cases may harbor one of several possible translocations, each resulting in a fusion gene containing a portion of the EWSR1 gene and a member of the ETS family of transcription factors.","Cancer"
"H00207","Rhizomelic chondrodysplasia punctata","Rhizomelic chondrodysplasia punctata (RCDP) is a lethal autosomal recessive disease associated with impaired peroxisomes characterized by proximal limb shortening, severely disturbed endochondrial bone formation, and mental retardation. RCDP1 is peroxisome biogenesis disorder caused by mutation of peroxisomal biogenesis factor 7(PEX7) genes. RCDP2 and RCDP3 are single peroxisomal enzyme deficiencies caused by mutation of GNPAT and AGPS. Both of them are key enzymes in the biosynthesis of ether phospholipids localized in peroxisomes.","Congenital disorder of metabolism; Congenital malformation"
"H02134","Microphthalmia with limb anomalies","Microphthalmia with limb anomalies (MLA), also known as Waardenburg anophthalmia syndrome or ophthalmoacromelic syndrome, is a rare autosomal-recessive disorder, presenting with unilateral or bilateral microphthalmia, clinical anophthalmia, and limb abnormalities such as syndactyly, brachydactyly, camptodactyly, synostosis, hip dislocation, absence, or hypoplasia of fibula, and bowed tibia. In addition, other organs may be affected (long-bone hypoplasia; renal, venous, and vertebral anomalies). It has been shown that mutations in SMOC1 gene cause this disorder.","Congenital malformation"
"H00663","Restrictive dermopathy","Restrictive dermopathy (LD) is a rare, lethal autosomal recessive genodermatosis caused by mutations in either LMNA or ZMPSTE24. Manifestations include a tight, thin, translucent skin, typical face, multiple joint contractures, enlarged fontanelles, and dysplasia of clavicles.","Congenital malformation"
"H01583","Hydroxykynureninuria","Hydroxykynureninuria, also known as xanthurenic aciduria is autosomal recessive disorder of tryptophan metabolism. It is characterized by excessive output of xanthutrenic acid, 3-hydroxykynurenine, and kynurenine in urine. This disease is caused by homozygous mutation in the KYNU gene, which encodes kynureninase. Kynureninase is an enzyme in the catabolic pathway of tryptophan metabolism. Some of these deficiencies lead to pellagra or mild pellagra-like symptoms, while it was reported in some patients no symptom of niacin deficiency was observed. The different clinical outcomes could be explained by differences in the intake of niacin. The sufficient intake of niacin could prevent depletion in some patients despite their impaired niacin synthesis.","Inherited metabolic disease"
"H00451","Osteoporosis-pseudoglioma syndrome","Osteoporosis-pseudoglioma syndrome (OPPG) is inherited as an autosomal recessive condition and is characterized by severe congenital osteoporosis with blindness. Mutations in LRP5 causes OPPG.","Congenital malformation"
"H02306","Chondrodysplasia with joint dislocations, GPAPP type","Chondrodysplasia with joint dislocations, GPAPP type is characterized by short stature, chondrodysplasia with brachydactyly, congenital joint dislocations, cleft palate, and facial dysmorphism. It is caused by mutations in IMPAD1, the gene encoding Golgi-resident PAP phosphatase (gPAPP). IMPAD1 inactivation has been shown to produce chondrodysplasia with abnormal joint formation and impaired proteoglycan sulfation.","Congenital malformation"
"H01745","Cardiofaciocutaneous syndrome","Cardio-facio-cutaneous (CFC) syndrome is a congenital disorder characterized by short stature, a characteristic face, cardiac defects, developmental delay and mental retardation. Affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial characteristics include high forehead, down-slanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears. CFC can be caused by mutations in BRAF, KRAS, MEK1, and MEK2, encoding components of the RAS-MAPK pathway.","Congenital malformation"
"H00697","X-linked myopathy with postural muscle atrophy","X-linked myopathy with postural muscle atrophy (XMPMA) is characterized by the combined presentation of weakness and atrophy of postural muscles (scapuloperoneal weakness and bent spine) with a pseudoathletic phenotype where alternative muscle groups are hypertrophic. Linkage studies and haplotype analysis followed by direct gene sequencing have identified five mutations in the FHL1 gene in patients with XMPMA.","Nervous system disease; Musculoskeletal disease"
"H01577","Essential tremor","Essential tremor (ET) is a neurological disorder that is considered to be one of the most common adult-onset movement disorders. ET is typically characterized by rhythmic, involuntary shaking of one or more parts of the body, and occurs exclusively during voluntary movements (action tremor) or in positions against gravity (postural tremor). The phenotypic severity of ET is variable, as evidenced by the existence of both highly disabling and milder forms of the disease. There are three subtypes of ET, namely hereditary, sporadic, and senile, and most studies indicate that ET is a hereditary disorder in more than half of affected individuals (and presumably has autosomal-dominant inheritance). The diagnostic approach includes obtaining a history, physical examination, and laboratory tests. At present, there are no validated serologic, radiologic, or pathological markers.","Nervous system disease"
"H01113","Acid phosphatase deficiency","Acid phosphatase deficiency is caused by defects in ACP2, that encodes the beta subunit of lysosomal acid phosphatase. The clinical features are intermittent vomiting, hypotonia, lethargy, opisthotonos, terminal bleeding, and death in early infancy.","Inherited metabolic disease; Lysosomal storage disease"
"H01321","Pneumococcal disease","Pneumococcal disease (PD) is infectious disease caused by Streptococcus pneumoniae (pneumococcus). PD is particularly common in younger children and in older adults and is roughly divided into invasive and non-invasive disease; the former refers to infections in which the microorganism is isolated from normal sterile body sites, such as the blood or the cerebrospinal fluid. Non-invasive PD can principally be divided into sinusitis, acute otitis media, and community-acquired pneumonia. S. pneumoniae remains the most common bacterial cause of community-acquired pneumonia. The invasive PD burden is mainly determined by pneumococcal meningitis, bacteremic pneumococcal pneumonia, and pneumococcal bacteremia without a primary focus. Incidence and mortality rates of both non-invasive and invasive disease have changed as a result of pneumococcal vaccination in children. However, especially elderly patients with comorbidities remain vulnerable to morbidity and mortality caused by PD.","Infectious disease"
"H00800","Loeys-Dietz syndrome","Loeys-Dietz syndrome (LDS) is an autosomal dominant disorder characterized by arterial aneurysms and dissections, pectus excavatum, craniosynostosis, cleft palate, congenital heart disease, and thin, translucent skin. LDS results from mutations in the TGF beta receptor genes. LDS has been subdivided in LDS1 and LDS2 on the basis of the presence or the absence of craniofacial involvement, respectively. LDS3 is associated with early-onset osteoarthritis and caused by mutation in the SMAD3 gene. LDS4 and LDS5 are caused by mutation in the TGFB2 and TGFB3 gene, respectively.","Developmental disorder; Cardiovascular disease"
"H00458","Syndromic craniosynostoses","Craniosynostosis is the premature fusion of the cranial sutures and secondary distortion of skull shape. Syndromic craniosynostosis typically involves cranial sutures plus central nervous system and extracranial skeletal changes. The genes most frequently mutated are FGFRs.","Congenital malformation"
"H01328","Aspergillosis","Pulmonary aspergillus infections can be classified based on clinical syndromes into saprophytic infections, allergic disease and invasive disease. Invasive pulmonary aspergillosis, occurring in immunocompromised patients, reflects the most serious disease with a high case-fatality rate. Of the 185 recognized species of Aspergillus, 20 are known to cause infections in humans. Aspergillus fumigatus accounts for about 65 percent of all invasive infections in humans and is the mostly encountered species in pulmonary infections. Aspergillus flavus, Aspergillus niger, Aspergillus terreus and Aspergillus nidulans are less frequently causes of invasive and pulmonary infections.","Infectious disease"
"H01926","Ventricular septal defect","Ventricular septal defect (VSD) is the most common type of cardiovascular developmental anomaly and is an important risk factor for the substantially increased morbidity and mortality in newborns. Congenital heart disease (CHD) is divided into more than 30 subtypes based on the cardiac or vascular abnormalities, of which VSD, atrial septal defect (ASD) [DS:H00546], tetralogy of Fallot (TOF) [DS:H00549], and Holt-Oram syndrome (HOS) [DS:H00433] are clinically the most common. VSDs can exist in isolation, can be complicated by additional intracardiac lesions, or can be part of more complex combinations, such as TOF, double outlet right ventricle [DS:H00918], or functionally univentricular hearts [DS:H01787]. Congenital VSDs arise from perturbations of cardiac development during embryogenesis and both environmental and genetic risk factors have been implicated in VSDs. Growing evidence highlights the key role of several transcription factors, including GATA4, in septogenesis.","Cardiovascular disease"
"H00655","McLeod syndrome","McLeod syndrome is an X-linked multisystem disorder including the CNS (chorea, epilepsy), the PNS (axonal polyneuropathy), and the blood cells (acanthocytosis of the erythrocytes) characterized by late onset abnormalities in the neuromuscular and hematopoietic systems. Mild myopathy is a common manifestation in most cases. Patients often present with mild, asymptomatic hyperCKemia. The absence of the XK membrane transport protein seems to be causative.","Nervous system disease"
"H01787","Univentricular heart","Univentricular heart is a term used to describe a wide variety of structural cardiac abnormalities associated with a functional single ventricular chamber. Truly solitary ventricles are exceedingly rare. It is generally agreed that the atrioventricular connection is central in defining the univentricular heart. More specifically, the well-developed ventricle may be designated left, right, or indeterminate. Clinical manifestations hinge on the presence or absence of pulmonary outflow obstruction. Without pulmonary stenosis, infants with low pulmonary resistance present with signs and symptoms typical of large left-to-right shunting, ie, congestive heart failure and failure-to-thrive. A certain degree of pulmonary stenosis is physiologically desirable to prevent pulmonary overcirculation. However, severe pulmonary stenosis or atresia may result in profound hypoxemia and cyanosis.","Developmental disorder; Cardiovascular disease"
"H02102","Myhre syndrome","Myhre syndrome is a developmental disorder characterized by reduced growth, generalized muscular hypertrophy, facial dysmorphism, deafness, cognitive deficits, joint stiffness, and skeletal anomalies. Heterozygous missense mutations in SMAD4 cause this disease. SMAD4 plays a pivotal role in the bone morphogenetic pathway and TGF-beta signaling.","Congenital malformation"
"H02330","Pancreatic lipase deficiency","Congenital pancreatic lipase deficiency is a rare autosomal recessive exocrine pancreatic failure characterized by decreased absorption of dietary fat and greasy voluminous stools, but apparent normal development and an overall good state of health. It has been reported that PNLIP mutations are causative for the phenotype.","Endocrine and metabolic disease"
"H00467","Fibular hypoplasia and complex brachydactyly","Fibular hypoplasia and complex brachydactyly (DuPan syndrome), inherited as an autosomal recessive trait, is characterized by fibula aplasia and severe limb shortening. Affected individuals were reported to be homozygous for a GDF5 missense mutation.","Congenital malformation"
"H00003","Acute myeloid leukemia","Acute myeloid leukemia (AML) is a disease that is characterized by uncontrolled proliferation of clonal neoplastic cells and accumulation in the bone marrow of blasts with an impaired differentiation program. AML accounts for approximately 80% of all adult leukemias and remains the most common cause of leukemia death. Two major types of genetic events have been described that are crucial for leukemic transformation. A proposed necessary first event is disordered cell growth and upregulation of cell survival genes. The most common of these activating events were observed in the RTK Flt3, in N-Ras and K-Ras, in Kit, and sporadically in other RTKs. Alterations in myeloid transcription factors governing hematopoietic differentiation provide second necessary event for leukemogenesis. Transcription factor fusion proteins such as PML-RARalpha (in Acute promyelocytic leukemia, a subtype of AML), AML-ETO or PLZF-RARalpha block myeloid cell differentiation by repressing target genes. In other cases, the transcription factors themselves are mutated.","Cancer"
"H00231","Hereditary elliptocytosis","Hereditary elliptocytosis (HE) is an autosomal dominant hematologic disorder characterized by elliptically shaped erythrocytes and a variable degree of hemolytic anemia caused by fragility of the erythrocyte membrane skeleton due to defects in alpha-spectrin, beta-spectrin, or protein 4.1.","Hematologic disease"
"H01919","Proud syndrome","Proud syndrome is a syndromic X-linked mental retardation, characterized by agenesis of the corpus callosum, and abnormal genitalia. ARX is considered to have an important role in neuronal proliferation, interneuronal migration and differentiation in the embryonic brain, and also in the differentiation of the testis. Phenotypes associated with ARX mutations include both brain malformation and non-malformation syndromes. Premature termination mutations and missense mutations in the homeobox domain cause malformation syndromes such as Proud syndrome.","Congenital malformation"
"H01125","Hereditary pyropoikilocytosis","Hereditary pyropoikilocytosis (HPP) is a recessively inherited form of hemolytic anemia characterized by peripheral blood morphology presenting with striking anisopoikilocytosis with red cell fragmentation and microspherocytes. Erythrocytes from most HPP patients exhibit qualitative and quantitative abnormalities of the erythrocyte membrane protein spectrin, the principal structural component of the erythrocyte membrane skeleton. Qualitative spectrin defects are typically associated with missense mutations that lead to abnormal spectrin self-association, a process critical for membrane structure and function.","Hematologic disease"
"H01317","Aggressive periodontitis","Aggressive periodontitis is a disease of the periodontium occurring in an otherwise healthy adolescent, which is characterized by a rapid loss of alveolar bone around more than one tooth of the permanent dentition. Because it tends to have a familial aggregation, host predisposition seems to play a key role in the pathogenesis of aggressive periodontitis. It occurs in localized and generalized forms.","Infectious disease"
"H01773","4p deletion syndrome","4p deletion syndrome, also known as Wolf-Hirschhorn syndrome (WHS), is a congenital disorder associated with various deformities. WHS is caused by deletion of the WHS critical resion (WHSCR) of chromosome 4p16.3. Because WHS is a contiguous gene deletion syndrome, loss of one copy of a single gene or the synergistic effects of loss of two or more genes could give rise to the features of WHS. The 'Greek warrior helmet appearance' is the most characteristic feature and refers to the facial view with prominent glabella, high arched eyebrow, broad nasal bridge and hypertelorism. Developmental delay and intellectual disability of variable degree is present in all. Seizures occur in 90% to 100% of children. Other findings include skeletal anomalies, congenital heart defects, hearing loss, urinary tract malformations, and structural brain abnormalities. Incidence is estimated to be about 1:50.000 births with a 2:1 female: male ratio.","Chromosomal abnormality"
"H00493","Heparan sulfate proteoglycan gene defects","Defects in heparan sulfate proteoglycans (HSPGs), which present in cartilage, are associated with skeletal growth disorders. Mutations in either HS biosynthetic enzymes or HS proteoglycan core proteins have been reported so far.","Congenital malformation"
"H01541","Argentine hemorrhagic fever","Argentine hemorrhagic fever is an infectious disease caused by Junin virus (JUNV), a New World arenavirus in the Arenaviridae family of -ssRNA viruses, and transmitted by rodents. JUNV was first isolated in 1958 in Argentine.","Infectious disease"
"H01921","MICPCH syndrome","Microcephaly with pontine and cerebellar hypoplasia (MICPCH) syndrome is a rare X-linked mental retardation syndrome, generally seen in girls, characterized by severe neurodevelopmental delay, microcephaly, and pontine and cerebellar hypoplasia. MICPCH syndrome is caused by inactivating calcium/calmodulin-dependent serine protein kinase (CASK) gene mutations. CASK is a multi-domain scaffolding protein that interacts with the transcription factor TBR1 and regulates expression of genes involved in cortical development such as RELN.","Congenital malformation"
"H00699","Central core disease","Central core disease (CCD) is an inherited neuromuscular disorder characterized by central cores on muscle biopsy and clinical features of a congenital myopathy. CCD is usually inherited as an autosomal dominant trait but recessive inheritance has been recently described in few families. The clinical phenotype of dominantly inherited CCD is variable but usually mild and non-progressive; however, more severe forms including the fetal akinesia syndrome have also been reported associated with recessive or de novo dominant mutations. CCD typically presents in infancy with hypotonia and motor developmental delay and is characterized by predominantly proximal weakness pronounced in the hip girdle. CCD is due to mutations in the skeletal muscle ryanodine receptor (RYR1) gene, encoding the principal skeletal muscle sarcoplasmic reticulum calcium release channel (RyR1). Altered excitability and/or changes in calcium homeostasis within muscle cells due to mutation-induced conformational changes of the RyR protein are considered the main pathogenetic mechanisms.","Nervous system disease; Musculoskeletal disease"
"H01579","Congenital symmetric circumferential skin creases","Congenital symmetric circumferential skin creases, also known as Michelin tire baby syndrome, is a rare genetic disorder characterized by generalized folding of excess skin. This feature was first described in 1969, then subsequent reports described variable additional features, such as intellectual disability (ID), facial dysmorphism, and cardiac and genital anomalies. It has been reported that mutations in either MAPRE2 or TUBB underlie the genetic origin of this syndrome. MAPRE2 encodes a member of the microtubule end-binding family of proteins that bind to the guanosine triphosphate cap at growing microtubule plus ends, and TUBB encodes a beta-tubulin isotype that is expressed abundantly in the developing brain.","Congenital malformation"
"H02308","Immunodeficiency-centromeric instability-facial anomalies syndrome","Immunodeficiency, centromeric instability and facial dysmorphism (ICF syndrome) is a genetically heterogeneous autosomal recessive disorder. It is characterized by recurrent and often fatal respiratory and gastrointestinal infections as a consequence of hypogammaglobulinemia in the presence of B cells. Nearly all patients also present with distinct facial anomalies. Centromeric instability is the cytogenetic hallmark of ICF syndrome. Mutations in the DNA methyltransferase 3B (DNMT3B) gene account for about 50% of ICF cases, while about 30% of cases have mutations in the ZBTB24 gene. Recently, it has been reported that mutations in CDCA7 and HELLS cause ICF syndrome.","Immune system disease"
"H00807","Nocturnal frontal lobe epilepsy","Nocturnal frontal lobe epilepsy (ENFL) is characterized by nocturnal, frequent, brief and stereotypic seizures. Ictal video electroencephalographic (EEG) studies have revealed partial seizures originating from the frontal lobe but also in parts of the insula, suggesting a defect of a broader network. Mutations in CHRNA4, CHRNB2, and CHRNA2, which encodes the alpha4-, beta2-, and alpha2-subunit of neuronal nicotinic acetylcholine receptor, have been reported. These mutations are concentrated in the pore-forming M2 transmembrane segments.","Nervous system disease"
"H00209","Menkes syndrome","Menkes disease (MD) is an X-linked recessive disorder of copper deficiency caused by mutation of a copper-transporting P-type ATPase, resulting in dysfunction of copper-dependent enzymes. The patients with classical MD have severe developmental and neurological impairments due to subnormal amount of copper in the brain and a variety of symptoms such as connective tissue abnormalities, tortuosity of blood vessels and peculiar hair. Most of the classical MD patients die before the age of 3 years.","Inherited metabolic disease; Nervous system disease; Skin and connective tissue disease"
"H00494","Desbuquois syndrome","Desbuquois syndrome is an autosomal recessive chondrodysplasia. Highly characteristic appearance of proximal femur, called 'Swedish key', is reported in the disease. Mutations in the calcium-activated nucleotidase 1 gene (CANT1) and xylosyltransferase 1 (XYLT1) have been identified.","Congenital malformation"
"H01546","Mayaro fever","Mayaro fever is an infectious disease caused by Mayaro virus (MAYV), an alphavirus in the Togaviridae family of +ssRNA viruses, and transmitted by Haemagogus mosquitoes. MAYV was first isolated in 1954 in Trinidad.","Infectious disease"
"H01774","Hyperostosis corticalis generalisata","Hyperostosis corticalis generalisata, also known as Van Buchem disease (VBCH), is autosomal recessive disease. This disease is characterized by progressive bone overgrowth, with narrowing of the neuroforamina in the skull causing cranial neuropathies. VBD is due to a homozygous deletion of a 52-kb regulatory element 35 kb downstream of the SOST gene, which leads to impaired production of sclerostin. Sclerostin, the gene product of SOST, is an inhibitor of the canonical Wnt signaling pathway. VBCH phenotype can be caused by mutation in the LRP5 gene.","Musculoskeletal disease"
"H01310","Multi-minicore disease","Multi-minicore Disease (MmD) is a recessively inherited neuromuscular disorder characterized by multiple cores on muscle biopsy and clinical features of a congenital myopathy. It is morphologically defined by localized multiple areas of mitochondrial depletion and sarcomere disorganization, running to a limited extent along the longitudinal axis of muscle fiber ('minicores'). Marked clinical variability corresponds to genetic heterogeneity. Mutations in the SEPN1 gene have been identified in patients with the classic axial phenotype characterized by spinal rigidity, early scoliosis, and respiratory impairment, whereas mutations in the RYR1 gene have been associated with a wider range of clinical features comprising external ophthalmoplegia, distal weakness and wasting or predominant hip girdle involvement.","Nervous system disease; Musculoskeletal disease"
"H01122","Congenital pulmonary alveolar proteinosis","Congenital pulmonary alveolar proteinosis is also known as pulmonary surfactant metabolism dysfunction (SMDP). It is caused by one of the three different genes associated with surfactant metabolism in type II epithelial cells and characterized by respiratory distress after birth. Congenital PAP is also associated with mutations in CSF2RA and CSF2RB genes, encoding alpha and beta chains of the GM-CSF receptor.","Respiratory disease"
"H00236","Congenital polycythemia","Familial and congenital polycythemia/erythrocytosis includes a heterogeneous group of disorders with the common characteristic of an absolute increased red cell mass caused by inherited defects in hypoxia sensing. In primary polycythemias there is an innate defect in the hematopoietic progenitors which allows constitutive overproduction whereas in secondary polycythemias normal progenitors are acted on by serum erythropoietin.","Hematologic disease"
"H00838","Congenital fibrosis of the extraocular muscles","Congenital fibrosis of the extraocular muscles (CFEOM) describes a group of rare congenital eye movement disorders that result from the dysfunction of all or part of the oculomotor (CN 3) and the trochlear (CN 4) nerves, and/or the muscles these nerves innervate. CFEOM is characterized by non-progressive, restrictive ophthalmoplegia of the extraocular muscles and congenital blepharoptosis. Several clinical phenotypes for familial CFEOM have been delineated.","Nervous system disease"
"H00004","Chronic myeloid leukemia","Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of a pluripotent stem cell. The natural history of CML has a triphasic clinical course comprising of an initial chronic phase (CP), which is characterized by expansion of functionally normal myeloid cells, followed by an accelerated phase (AP) and finally a more aggressive blast phase (BP), with loss of terminal differentiation capacity. On the cellular level, CML is associated with a specific chromosome abnormality, the t(9; 22) reciprocal translocation that forms the Philadelphia (Ph) chromosome. The Ph chromosome is the result of a molecular rearrangement between the c-ABL proto-oncogene on chromosome 9 and the BCR (breakpoint cluster region) gene on chromosome 22. The BCR/ABL fusion gene encodes p210 BCR/ABL, an oncoprotein, which, unlike the normal p145 c-Abl, has constitutive tyrosine kinase activity and is predominantly localized in the cytoplasm. While fusion of c-ABL and BCR is believed to be the primary cause of the chronic phase of CML, progression to blast crisis requires other molecular changes. Common secondary abnormalities include mutations in TP53, RB, and p16/INK4A, or overexpression of genes such as EVI1. Additional chromosome translocations are also observed,such as t(3;21)(q26;q22), which generates AML1-EVI1.","Cancer"
"H02337","Skraban-Deardorff syndrome","Skraban-Deardorff syndrome is characterized by intellectual disability with seizures, abnormal gait, and distinctive facial features. It has been reported that WDR26 haploinsufficiency causes this disease.","Congenital malformation"
"H00460","Hand-foot-genital syndrome","Hand-foot-genital syndrome is very rare dominantly inherited condition affecting the development of the limbs and genitourinary tract.","Congenital malformation"
"H00652","Solitary median maxillary central incisor syndrome","Solitary median maxillary central incisor (SMMCI) syndrome is a rare dental anomaly characterized by the presence of a central incisor with symmetric crown form positioned at the maxillary mid-axis. Missense mutations in the SHH, a key player in ventral axis patterning, is associated with the disorder.","Congenital malformation"
"H01780","Non-dystrophic myotonia","Non-dystrophic myotonias are rare diseases caused by mutations in key skeletal muscle ion channels. The major clinical manifestation is muscle stiffness as a consequence of the myotonia. Additional common symptoms include pain, weakness and fatigue. They are considered to be distinct from myotonic dystrophy because of the absence of progressive weakness and systemic features. Non-dystrophic myotonias include myotonia congenita, paramyotonia congenita, and sodium channel myotonias.","Nervous system disease; Musculoskeletal disease"
"H02105","Prohormone convertase 1/3 deficiency","Proprotein convertase 1/3 (PC1/3) deficiency is a rare autosomal recessive disorder caused by mutations in the PCSK1 gene. It is associated with early-onset obesity, severe malabsorptive diarrhea, certain endocrine abnormalities, and dysregulation of glucose homeostasis. PC1/3 is an endoprotease that processes many prohormones expressed in endocrine and neuronal cells.","Endocrine and metabolic disease"
"H02354","Orf","Orf is a highly contagious zoonotic infectious disease caused by orf virus, a parapoxvirus in the Poxviridae family of dsDNA viruses. Orf virus is transmitted to humans by direct or indirect contact with sheep and goats. Its viability on the ground and the ability to reinfect the host has contributed to the spread and maintenance of the infection in many species.","Infectious disease"
"H00403","Disorders of nucleotide excision repair","Mutations in genes on the nucleotide excision repair pathway are associated with diseases, such as xeroderma pigmentosum (XP), Cockayne syndrome (CS) and trichothiodystrophy (TTD). XP is caused by mutations in XPA, ERCC3/XPB, XPC, ERCC2/XPD, DDB2/XPE, ERCC4/XPF, ERCC5/XPG and POLH. XP is classified into eight genetic complementation groups by the present. In this inside, 7groups from the XP-A group to the G group show the abnormality in NER. The symptoms of XP begin in early life. Severe sunburn and blistering occurs in a half of patients, and all show early extensive freckling. Cancer incidence for individuals with XP under 20 years of age is 2,000 times as high as incidence in the general population. Neurodegeneration can be correlated with mutations in specific XP genes (XPA, ERCC3, ERCC2 and ERCC5). Some patients of XP- A develop neurologic symptoms or a more severe clinical phenotype known as de Sanctis-Cacchione syndrome, associated with mutations in the ERCC6 gene. CS is caused by mutations in ERCC8/CSA, ERCC6/CSB. CS is predominantly a developmental and neurological disorder. It results in a severely reduced lifespan but is not linked to an increased incidence of cancer. The three of the XP genes (ERCC2, ERCC3, and ERCC5) are also found to be mutated XP/CS patients (exhibiting both XP and Cockayne's symptoms). ERCC6 is a cause of UV-sensitive syndrome (UVS) which is characterized by photosensitivity and mild freckling but without neurological abnormalities or skin tumors. TTD is a premature aging syndrome, with the hallmark feature of brittle hair and nails, ichthyosis, and progressive mental and physical retardation. Within photo-sensitive TTD, three TFIIH coding genes (ERCC2, ERCC3, and TTDA/GTF2H5) are implicated. Cerebro-oculo-facio-skeletal (COFS) syndrome is rare autosomal recessive disorder with microcephaly, severe mental retardation, and death in childhood. COFS can result from mutations in ERCC1, ERCC2, ERCC5 and ERCC6.","Congenital malformation"
"H00631","Cornelia de Lange syndrome","Cornelia de Lange syndrome (CdLS) is a heterogeneous developmental disorder characterized by facial dysmorphia, upper limb defects, hirsutism, and gastrointestinal abnormalities. About 65% of patients harbor mutations in genes that encode subunits or regulators of the cohesin complex, including NIPBL, SMC1A, SMC3, RAD21, and HDAC8.","Congenital malformation"
"H02166","Saint Louis encephalitis","Saint Louis encephalitis is an infection of the central nervous system caused by Saint Louis encephalitis virus (SLEV), a flavivirus in the Flaviviridae family of +ssRNA viruses, and transmitted by Culex mosquitoes. SLEV was first isolated in 1933 in St Louis, Missouri, USA.","Infectious disease"
"H00255","Hypogonadotropic hypogonadism","Hypogonadotropic hypogonadism (HH) or secondary hypogonadism is defined as a clinical syndrome that results from gonadal failure due to abnormal pituitary gonadotropin levels. HH may result from either absent or inadequate hypothalamic gonadotropin releasing hormone (GnRH) secretion or failure of pituitary gonadotropin secretion. HH can be congenital or acquired. Congenital HH is clinically and genetically heterogeneous. Clinically, the disorder is characterized by an absence of puberty and infertility. The genetic condition is classically divided in 2 groups based on the presence or absence of olfaction dysfunction. Around 50-60% of the affected individuals exhibit anosmia or hyposmia in association with IHH, defining Kallmann syndrome. Acquired HH can be caused by drugs, infiltrative or infectious pituitary lesions, hyperprolactinemia, encephalic trauma, pituitary/brain radiation, exhausting exercise, abusive alcohol or illicit drug intake, and systemic diseases such as hemochromatosis, sarcoidosis and histiocytosis X.","Endocrine disease"
"H01387","Activated PI3K-delta syndrome","Activated PI3K-delta syndrome (APDS) is a primary immunodeficiency characterized by recurrent respiratory infections, progressive airway damage, lymphopenia, increased circulating transitional B cells, increased immunoglobulin M, and reduced immunoglobulin G2 levels in serum and impaired vaccine responses. A dominant gain-of-function mutation has been found in the p110-delta protein, the catalytic subunit of phosphoinositide 3-kinase delta (PI3K-delta), encoded by the PIK3CD gene.","Primary immunodeficiency"
"H02502","Joint laxity, short stature, and myopia","Joint laxity, short stature, and myopia (JLSM) is a rare autosomal recessive connective-tissue disease caused by mutations in GZF1. JSLM is characterized by severe myopia and significant articular involvement. GZF1 encodes a transcription factor which is expressed in the eyes and limbs.","Congenital malformation"
"H01989","Beare-Stevenson syndrome","Beare-Stevenson cutis gyrata syndrome is an extremely rare autosomal dominant condition characterized by the furrowed skin disorder called cutis gyrata, acanthosis nigricans, craniosynostosis, craniofacial dysmorphism, digital anomalies, umbilical and anogenital abnormalities and early death. Mutations of FGFR2 have been identified.","Congenital malformation"
"H00067","Friedreich ataxia","Friedreich ataxia is one of the most common forms of autosomal recessive ataxia caused by severely reduced levels of frataxin as a result of a large GAA triplet-repeat expansion within the first intron of the frataxin gene. Frataxin deficiency is thought to cause generation of reactive oxygen species, reactive nitrogen species and mitochondrial dysfunction.","Neurodegenerative disease"
"H01373","Achromobacter xylosoxidans infection","Achromobacter xylosoxidans, also known as Alcaligenes xylosoxidans, is an environmental opportunistic pathogen that causes nosocomial infections targeting immunocompromised patients suffering from cancer, advanced HIV, diabetes mellitus or chronic renal failure. This bacterium can rarely cause keratitis in patients who had worn contact lenses.","Infectious disease"
"H00093","Combined immunodeficiency","The term combined immunodeficiency (CID) is used to distinguish patients with low, but not absent, T-cell function from those with severe CID (SCID) characterized by profound deficiencies of T- and B-cell (and sometimes NK- cell) function. Hyper-IgM syndrome (HIM) represents a group of distinct entities characterized by defective normal or elevated IgM in the presence of diminished IgG and IgA levels. The genetic anomaly in X-linked hyper-IgM syndrome has been mapped to Xq26, and resides in mutations of the CD40 ligand gene. Missense mutation in exon 7 of the common gamma chain (IL2RG) causes a moderate form of X-linked CID. This point mutation in IL2RG leads to a less severe degree of deficiency in cellular and humoral immunity than that seen in XSCID. Two related deficiencies of recombination activating genes, RAG1 and RAG2 result in a spectrum of SCID called RAG1/RAG2 deficiency and Omenn syndrome. Mutations that lead to total absence of RAG1 or RAG2 gene product (null mutations) are known to lead to SCID without mature lymphoid cells, whereas mutations that result in partial V(D)J recombinase activity due to missense mutation on at least one allele lead to Omenn syndrome. Mutations of both TAP1 and TAP2 genes result in deficient expression of class I HLA proteins on the cell surface with defects in natural killer cell cytotoxicity. Defective expression of major histocompatibility complex (MHC) class II molecules account for 5% of SCID. The genetic lesions responsible for this syndrome do not lie within the MHC-II locus itself, but reside instead in genes encoding transcription factors, RFX5, RFXAP, RFXANK(B), and CIITA, controlling MHC-II expression. ZAP-70 deficiency is inherited in an autosomal recessive manner. Recurrent and opportunistic infections occur within the first year of life. The mutations in genes responsible for CRAC channel function, ORAI1 and STIM1, cause the defect in Ca2+ influx.","Primary immunodeficiency"
"H01141","Human monocytic ehrlichiosis","Human monocytic ehrlichiosis is a tick-borne infectious disease caused by Ehrlichia chaffeensis that infects mononuclear phagocytic cells. The bacterium is maintained in nature involving many vertebrate species such as deer that serve as competent reservoirs for the bacterium and as sources of blood for tick vectors. Patients experience fever, malaise, low-back pain, or gastrointestinal symptoms.","Infectious disease"
"H01525","22q11.2 deletion syndrome","The 22q11.2 deletion syndrome is the most common microdeletion disorder with an estimated prevalence of 1 in 3000-6000 live births. Most of the patients show the common 3 Mb deletion, but proximal 1.5 Mb deletion and unusual deletions located outside the common deleted region, have been detected. Various syndromes have been associated with 22q11.2 deletion including DiGeorge syndrome (DGS), velocardiofacial syndrome (VCFS), conotruncal anomaly face syndrome (CTAF), and isolated and familial forms of cardiovascular malformation. Microdeletions of 22q11.2 have been found in more than 90% of patients with DGS and over 85% of VCFS/ CTAF patients. In addition, several patients with Opitz-GBBB syndrome have been reported with microdeletions of 22q11. The variability in the clinical expression of this disease is extremely wide. Classical features include congenital heart disease, velopharyngeal insufficiency or cleft palate, facial anomalies, speech and learning disabilities, neonatal hypocalcemia, and T-cell immune deficit. Nevertheless, the spectrum of anomalies associated with 22q11.2 deletion is becoming wider and wider. Some cardiovascular abnormalities are relatively specific for the syndrome. An interruption of the aortic arch, type-B (IAA-B) is associated with deletion 22q11 in approximately 50% of cases. Other defects including tetralogy of Fallot [DS:H00549], double outflow right ventricle, ventricular septal defect and an aberrant origin of the right subclavian artery are frequently found.","Chromosomal abnormality"
"H01717","Optic neuritis","Optic neuritis is a demyelinating inflammatory disease of the optic nerve that presents with an abrupt loss of vision. The majority of patients are between the ages of 20 and 50 years, with a mean age ranging from 30 to 35 years. It occurs more commonly in women than in men. The onset is usually with pain on eye movement in one eye and subacute visual loss. One-third of patients have a mildly edematous optic disc. The visual disturbance resolves in 95% of cases. Many cases of optic neuritis are associated with multiple sclerosis or neuromyelitis optica or can occur in isolation. Occasionally, optic neuritis can result from infectious processes involving the paranasal sinuses or occur in the course of a systemic viral infection. High-dosed intravenous methylprednisolone therapy speeds recovery but does not improve the final outcome. For patients judged to be at high risk of developing multiple sclerosis, immune prophylaxis with beta-interferon or glatiramer acetate is recommended.","Nervous system disease"
"H02192","Benign recurrent intrahepatic cholestasis","Benign recurrent intrahepatic cholestasis (BRIC) is a rare autosomal recessive inherited disorder characterized by intermittent episodes of severe cholestatic jaundice. It is caused by mutations in the ATP8B1 and ABCB11 genes, which are the same as in progressive familial intrahepatic cholestasis 1 and 2 (PFIC1 and PFIC2), and probably in at least one other as yet unidentified gene. While PFIC starts in infancy or early childhood and often leads to liver cirrhosis, BRIC typically appears before the second decade of life and has a more benign recurrent pattern. Occasionally BRIC will progress to the more severe and permanent form of PFIC.","Digestive system disease"
"H00864","Trichotillomania","Trichotillomania (TTM) is a chronic behavioral disorder characterized by the irresistible urge to pull out one's hair, resulting in noticeable hair loss. Mutations in SLITRK1 are found in patients with TTM.","Mental and behavioural disorder"
"H00058","Amyotrophic lateral sclerosis (ALS)","Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by a progressive degeneration of motor neurons in the brain and spinal cord. In 90% of patients, ALS is sporadic, with no clear genetic linkage. On the other hand, the remaining 10% of cases show familial inheritance, with mutations in SOD1, TDP43(TARDBP), FUS, or C9orf72 genes being the most frequent causes. In spite of such difference, familial ALS and sporadic ALS have similarities in their pathological features. Proposed disease mechanisms contributing to motor neuron degeneration in ALS are: impaired proteostasis, aberrant RNA processing, mitochondrial disfunction and oxidative stress, microglia activation, and axonal dysfunction.","Neurodegenerative disease"
"H02159","Familial cold autoinflammatory syndrome","Familial cold autoinflammatory syndrome (FCAS), also known as familial cold urticaria, is an autosomal dominant inflammatory disease that is characterized by episodes of rash, arthralgia, fever, conjunctivitis, and leukocytosis after generalized exposure to cold.","Immune system disease"
"H01728","Potter syndrome","Potter syndrome is a rare fatal disorder that occurs in sporadic and hereditary forms. It affects predominantly male babies and is accompanied by severe oligohydramnios, polycystic kidney, bilateral renal agenesis, and obstructive uropathy during middle gestational weeks. Renal failure is the main defect in Potter syndrome. Other characteristic features include premature birth, breech presentation, atypical facial appearance, and limb malformations. Severe respiratory insufficiency leads to a fatal outcome in most infants. Potter syndrome has been divided into 4 distinct subgroups. Potter syndrome type I is referred to as autosomal recessive polycystic kidney disease (ARPKD), type II as renal dysplasia, type III as autosomal dominant polycystic kidney disease (ADPKD), and type IV occurs when a longstanding obstruction in either the kidney or ureter leads to cystic kidneys or hydronephrosis. Particularly types II-IV can be part of many syndromes.","Congenital malformation"
"H00890","Azoospermia","Azoospermia is a disorder in which there is a complete absence of sperm in the semen. It is classified as obstructive azoospermia caused by problems with sperm transport and nonobstructive azoospermia caused by failure of spermatogenesis. Y-linked gene USP9Y has been implicated in moderate oligoasthenoteratozoospermia and azoospermia. SYCP3 mutations lead to complete infertility due to meiotic arrest.","Reproductive system disease"
"H01942","Glycogen storage disease type IV","Glycogen storage disease type IV (GSD-IV), also known as Andersen disease, is an autosomal recessive disorder of glycogen metabolism. GSD-IV is caused by mutations in the GBE1 gene, which encodes the glycogen branching enzyme. The typical presentation is liver disease of childhood, progressing to lethal cirrhosis.","Inherited metabolic disease"
"H01710","Mixed connective tissue disease","Mixed connective tissue disease (MCTD) is a rare autoimmune disease characterized by a combination of clinical features of systemic lupus erythematosus, systemic sclerosis, and polymyositis with elevated antibodies to U1 small nuclear ribonucleoprotein (U1-RNP). The most common clinical manifestations of this disease are Raynaud's phenomenon, arthralgias, swollen joints, esophageal dysfunction, muscle weakness and fingers sausage-like appearance. The disease can be serious with development of pulmonary, kidney, cardiovascular, gastrointestinal, and central nervous system manifestations. The worst prognosis and high mortality are associated with the presence of pulmonary disease. Therapy should be individualised for each patient to address the specific organs involved and the severity of underlying disease activity. Inflammatory manifestations usually respond to steroid treatment, whereas clinical sclerodermatous manifestations such as sclerodactyly, and pulmonary interstitial disease more often require cytotoxic immunosuppressive treatment.","Immune system disease"
"H02195","MEHMO syndrome","MEHMO syndrome is a rare X-linked syndrome characterised by mental retardation, epileptic seizures, hypogenitalism, microcephaly and obesity. It has been reported that MEHMO syndrome is associated with mutations in the X chromosome gene EIF2S3. EIF2S3 encodes the subunit of the eukaryotic translation initiation factor 2 (eIF2).","Congenital malformation"
"H01522","Zollinger-Ellison syndrome","Zollinger-Ellison syndrome (ZES) is a rare endocrinopathy caused by tumors of the pancreas and duodenum. These tumors, called gastrinomas, release gastrin to produce large amounts of acid that result in severe gastroesophageal peptic ulcer disease and diarrhea. Most ZES cases are sporadic, but about over 20 percent are caused by an inherited genetic disorder called multiple endocrine neoplasia type 1 (see H00247). The clinical presentation is not specific for this disease and there is overlap of symptoms similar to those of a peptic ulcer. The most common symptoms include abdominal pain and diarrhea, sometimes accompanied by heartburn, nausea, and weight loss. Peptic ulceration complicated by bleeding is present in 25% of patients, and is more frequently in patients with sporadic ZES than in those with MEN1. In addition, the gastrinomas may be cancerous. The cancer can be spread to other parts of the body, most commonly to regional lymph nodes and the liver. The treatment of the ZES includes surgical removal and medical management of gastric acid hypersecretion for the prevention of malignant transformation and the genesis of complications.","Endocrine and metabolic disease"
"H00094","Immunodeficiency associated with DNA repair defects","A number of genetically determined disorders collectively called as the chromosome breakage syndromes or DNA-repair disorders have a characteristic cytogenetic feature, chromosome instability. They are all autosomal recessive, show an increased tendency for chromosomal aberrations and to develop malignancies. Ataxia telangiectasia (AT), Nijmegen breakage syndrome (NBS), and an ataxia-like disorder (ATLD), are chromosome instability disorders that are defective in the ataxia telangiectasia mutated (ATM), NBS, and Mre11 genes, respectively. These genes are critical in maintaining cellular resistance to ionizing radiation (IR), which kills largely by the production of double-strand breaks (DSBs). Bloom syndrome involves a defect in the BLM helicase, which seems to play a role in restarting DNA replication forks that are blocked at lesions, thereby promoting chromosome stability. A point mutational change in DNA ligase I was identified in a unique immunodeficient individual who suffered recurrent sinopulmonary infection leading to bronchiectasis. A non-inactivating mutational change in DNA ligase IV has also been identified in a leukaemia patient, who was dramatically over-sensitive to radiotherapy.","Primary immunodeficiency"
"H01146","Aminoacylase 1 deficiency","Aminoacylase 1 deficiency is an autosomal recessive disease characterized by accumulation of N-acetyl amino acids in the urine. In affected individuals neurological findings such as febrile seizures, delay of psychomotor development and moderate mental retardation have been reported.","Congenital disorder of metabolism"
"H01374","Helicobacter cinaedi infection","Helicobacter cinaedi (previously called Campylobacter cinaedi) causes cellulitis, bacteremia and diarrhea frequently in immunocompromised patients and occasionally in immunocompetent individuals. In addition to these things, Nosocomial H. cinaedi infections have recently been reported.","Infectious disease"
"H00060","Dentatorubropallidoluysian atrophy (DRPLA)","Dentatorubropallidoluysian atrophy (DRPLA) is one of the CAG repeat diseases like Huntington's disease. It is caused by expansion of a CAG repeat in the atrophin 1 gene and shows various combinations of clinical symptoms depending on the age of onset. The clinical features of DRPLA include progressive myoclonus, seizure, and mental retardation in patients with an earlier onset (generally < 20 years) and cerebellar ataxia, choreoathetosis, and dementia in patients with a later onset (> 40 years).","Neurodegenerative disease"
"H00252","Congenital nephrogenic diabetes insipidus","Nephrogenic diabetes insipidus (NDI) is characterized by renal insensitivity to the antidiuretic effect of arginine vasopressin.","Urinary system disease"
"H01380","Bacterial vaginosis","Bacterial vaginosis (BV) flora is dominated by Gardnerella vaginalis and includes many anaerobic organisms as contrasted with normal lactobacillus-dominated vaginal flora. BV flora is thought to be related to vaginal discharge, poor pregnancy outcomes, pelvic inflammatory disease, postoperative wound infections, endometritis following elective abortions. Additionally, BV flora predisposes women to infection by HIV as well as other Sexually Transmitted Diseases (STDs).","Infectious disease"
"H02505","Atherosclerosis","Atherosclerosis is a chronic inflammatory disease marked by a narrowing of the arteries from lipid-rich plaques present within the walls of arterial blood vessels. It represents the root cause of the majority of cardiovascular diseases (CVDs) and their complications, including conditions such as coronary artery disease, myocardial infarction and stroke. Atherosclerosis develops as a result of the interactions of various genetic and environmental factors. Elevated cholesterol and LDLcholesterol (LDL-C) levels are the main risk factors that associated with the formation of atherosclerotic plaques and the development of atherosclerosis.","Cardiovascular disease"
"H00636","Tetra-amelia syndrome","Tetra-amelia syndrome (TETAMS) is an extremely rare condition characterized by the complete absence of all four limbs. Patients commonly have other anomalies involving the face, eyes, heart, nervous system, and urogenital system. Homozygous Wnt3 mutation is responsible for tetra-amelia. Recently, it has been reported that RSPO2 mutations cause tetra-amelia syndrome with lung aplasia.","Congenital malformation"
"H02161","Greig cephalopolysyndactyly syndrome","The Greig cephalopolysyndactyly syndrome (GCPS) is a multiple congenital anomaly syndrome. The clinical findings include hypertelorism, macrocephaly with frontal bossing, and polysyndactyly. GCPS is caused by loss of function mutations in the GLI3 transcription factor gene and is inherited in an autosomal dominant pattern.","Congenital malformation"
"H02353","Hyperekplexia and epilepsy","Hyperekplexia and epilepsy is also known as early infantile epileptic encephalopathy 8 (EIEE8) [DS:H00606]. It is a X-linked mental retardation and sensory hyperarousal, caused by mutations in ARHGEF9. Collybistin, encoded by ARHGEF9, is a RhoGEF family protein and highly expressed in the developing and adult brain.","Nervous system diseases"
"H00404","Erythema infectiosum","Erythema infectiosum, or fifth disease, is a benign pediatric condition caused by B19 parvovirus. It causes a mild, self-limiting 'slapped-cheek' facial rash with low-grade fever and malaise in immunocompetent children. Parvovirus B 19 also causes a wide range of clinical complications, including thrombocytopenia and neurological manifestations in immunocompromised patients and intrauterine fetal death in primary infected pregnant women.","Infectious disease"
"H00299","Shigellosis","Shigellosis (bacillary dysentery) is a foodborne enterobacterial infection caused by Shigella species. There are four subgroups of Shigella: S. dysenteriae, S. flexneri, S. boydii, and S. sonnei. Of these, S. flexneri is the most frequently observed worldwide, and S. dysenteriae causes severe disease with the highest fatality rate. Transmission usually occurs via contaminated food and water or through person-to-person contact.","Infectious disease"
"H00897","Pontocerebellar hypoplasia","Pontocerebellar hypoplasia (PCH) is a group of inherited progressive neurodegenerative disorders with prenatal onset. Up to now ten different subtypes have been reported. All subtypes share common characteristics, including hypoplasia/atrophy of cerebellum and pons, progressive microcephaly, and variable cerebral involvement. Mutations in three tRNA splicing endonuclease subunit genes were found to be responsible for PCH2, PCH4 and PCH5. Mutations in the nuclear encoded mitochondrial arginyl- tRNA synthetase gene underlie PCH6. PCH1 is caused by homozygous mutation in the VRK1 gene.","Neurodegenerative disease; Developmental disorder"
"H01945","Glycogen storage disease type VII","Glycogen storage disease type VII (GSD-VII), also known as Tarui disease, is an autosomal recessive disorder of glycogen metabolism. GSD-VII is caused by mutations in the PFKM gene, which encodes muscle phosphofructokinase. It is characterized by exercise-induced muscle symptoms such as premature fatigue, painful cramps, and myoglobinuria. Additional symptoms include hemolysis and myogenic hyperuricemia.","Inherited metabolic disease"
"H01179","Tungiasis","Tungiasis is a tropical ectoparasitosis caused by the permanent penetration of the female flea Tunga penetrans into the skin of its host. It is prevalent where people live in extreme poverty, occurring in many Latin American and African countries. The contamination occurs when walking barefoot in the sand.","Infectious disease"
"H02398","COVID-19","Coronavirus disease of 2019 (COVID-19) is a highly contagious respiratory infection that is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 infects alveolar epithelial cells [mainly alveolar epithelial type 2 (AEC2) cells] through the angiotensin-converting enzyme 2 (ACE2) receptor. Upon the occupancy of ACE2 by SARS-CoV-2, the increased serum level of free Angiotensin II (Ang II) due to a reduction of ACE2-mediated degradation promotes activation of the NF-kappa B pathway via Ang II type 1 receptor (AT1R), followed by  interleukin-6 (IL-6) production. SARS-CoV-2 also activates the innate immune system; macrophage stimulation triggers the overproduction of pro-inflammatory cytokines, including IL-6, and the 'cytokine storm', which results in systemic inflammatory response syndrome and multiple organ failure. The combined effects of complement activation, dysregulated neutrophilia, endothelial injury, and hypercoagulability appear to be intertwined to drive the severe features of COVID-19.","Infectious disease"
"H00609","Persistent Mullerian duct syndrome","Persistent Mullerian duct syndrome (PMDS) is a rare form of a 46,XY disorder of sex development, in which remnants of Mullerian ducts are seen in phenotypically normal males. The syndrome is caused either by a mutation in the Anti-Mullerian hormone (AMH) gene or the AMH receptor gene (AMHR2). AMH is secreted mainly by immature Sertoli cells at the time of sex differentiation in fetal life, and have a role in the regression of Mullerian ducts.","Reproductive system disease"
"H00863","Spondylo-megaepiphyseal-metaphyseal dysplasia","Spondylo-megaepiphyseal-metaphyseal dysplasia is a rare skeletal dysplasia. Its features are disproportionate short stature. On radiograph, defective ossification of vertebral bodies, enlarged epiphyses, and metaphyseal dysplasia are noted. It is inherited as an autosomal recessive trait.","Congenital malformation"
"H01170","Autosomal recessive spastic ataxia of Charlevoix-Saguenay","Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a distinct form of hereditary early-onset spastic ataxia related to progressive degeneration of the cerebellum and spinal cord. ARSACS is clinically characterized by spasticity, ataxia, polyneuropathy, retinal changes, and in some cases late cognitive decline. Patients demonstrate an unsteady gait and experience frequent falls as they learn to walk. ARSACS is caused by mutations in the SACS gene, encoding a large protein sacsin. A recent study demonstrated that sacsin may interact with the Hsp70 chaperone machinery, which is an important component of the cellular response towards aggregation prone mutant proteins that are associated with neurodegenerative diseases.","Nervous system disease"
"H01342","Zellweger syndrome","Zellweger syndrome (ZS) is the most severe form seen in the peroxisome biogenesis disorder, characterized by neurological dysfunction, craniofacial abnormalities, eye abnormalities, hepatomegaly, and chondrodysplasia punctata. This disease is caused by mutation of peroxisomal biogenesis factor (PEX) genes. Due to the deficiency of functional peroxisomes, several metabolite abnormalities are usually found in ZS patients. Typically, patients accumulate C27-bile acid intermediates.","Congenital disorder of metabolism"
"H00290","Aicardi-Goutieres syndrome","Aicardi-Goutieres Syndrome (AGS) is an autosomal recessive encephalopathy characterized by basal ganglia and white matter calcification in the presence of chronic cerebrospinal fluid lymphocytosis, and a raised level of cerebrospinal fluid IFNalpha. There is progressive neurological dysfunction resulting in a failure of development of expected physical and social skills. AGS presents in infancy and is lethal in ~40% of cases. It can be caused by mutations in the following genes, TREX1, RNaseH2 and SAMHD1 that lead to excessive intracellular accumulation of DNA and abnormal type I IFN metabolism.","Immune system disease"
"H01726","Membranoproliferative glomerulonephritis","Membranoproliferative glomerulonephritis (MPGN) represents a pattern of glomerular injury, characterized by mesangial proliferation and expansion, lobularization of the glomerular tufts and double contours. Classification of MPGN has been updated in the 2010s, and is now categorized according to the immunofluorescence microscopy findings. Until recently, the MPGNs have been distinguished according to the histological and ultra structural findings and were classified as MPGN type I, type II and type III. A new terminology that distinguishes immunoglobulin-mediated MPGN (ie, the former type I) from complement-mediated MPGN has been proposed. Immune-complexes mediated MPGN is caused by the deposition of immunocomplexes in the glomeruli. The immunocomplexes activate the classical pathway (CP) of complement and cause the deposition of complement factors or of the membrane attack complex (MAC) in the mesangium and capillary loops. The most frequent underlying disorders associated with immune complex MPGN include chronic infections, autoimmune diseases, and monoclonal gammopathies. The complement-mediated MPGN, termed C3 glomerulopathy, is characterised by defects in the alternative pathway of complement, in particular of factor H, or autoantibodies to complement-regulatory proteins (so-called C3 nephritic factors) leading to increased complement activation. The group includes dense deposit disease (DDD) and C3 glomerulonephritis. The two entities are distinguished on the basis of the immunohistological pattern of C3 and the electron microscopy detection of ribbon-like electron-dense deposits in the glomerular basement membrane in DDD, versus deposits of usual density in C3 glomerulonephritis.","Immune system disease; Urinary system disease"
"H01514","Landau-Kleffner syndrome","Landau-Kleffner syndrome (LKS) is an epileptic encephalopathy that usually manifests itself in children aged 3-8 years with previously normal development. All LKS patients have abnormal EEG that is compatible with the diagnosis of epilepsy, however, only 70% have clinical seizures. The main symptoms are acute or subacute aphasia with inability to recognise, process or interpret verbal and/or non-verbal sounds. Although the exact etiology of LKS remains unclear, families with mutations in the GRIN2A gene have been described, in which some members have LKS. Recent reports have implicated susceptibility genes (SRPX2, ELP4) to idiopathic focal epilepsies.","Nervous system disease; Mental and behavioural disorder"
"H02391","Infantile-onset multisystem neurologic, endocrine, and pancreatic disease","Infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD) is a novel intellectual disability phenotype caused by homozygous mutations in PTRH2. IMNEPD is characterized by intellectual disability, microcephaly, progressive ataxia, sensorineural deafness, peripheral neuropathy, exocrine pancreas insufficiency, and hypothyroidism. PTRH2 encodes a primarily mitochondrial protein involved in integrin-mediated cell survival and apoptosis signaling.","Congenital malformation"
"H02157","Short-rib thoracic dysplasia","Short-rib thoracic dysplasia (SRTD) is a group of autosomal recessive skeletal ciliopathies. The ciliary machinery has been implicated in more than a dozen disorders, now called ciliopathies. Primary cilia play a vital role in transduction of signals in the hedgehog pathway that is especially important in skeletal development.","Congenital malformation"
"H00600","Mullerian agenesis","Mullerian agenesis, also known as Mayer Rokitansky Kuster Hauser (MRKH) syndrome, is characterized by utero-vaginal atresia in an otherwise phenotypically normal female with a normal 46,XX karyotype. It has been reported that Mullerian aplasia and hyperandrogenism is caused by mutations in the WNT4 gene. WNT4, a secreted protein that suppresses male sexual differentiation, is thought to repress the biosynthesis of gonadal androgen in female mammals.","Reproductive system disease"
"H00432","Hereditary dentine disorders","Hereditary dentine disorders are divided into 5 types: 3 types of dentinogenesis imperfecta (DGI), and 2 types of dentin dysplasia (DD). DGI type I is inherited with osteogenesis imperfecta [DS:H00506]. It has been shown that mutations in the genes encoding collagen type 1, COL1A1 and COL1A2, underlie this condition. All other forms of DGI and DD except DD1, appear to result from mutations in the gene encoding dentine sialophosphoprotein (DSPP).","Digestive system disease"
"H02365","Helsmoortel-van der Aa syndrome","Helsmoortel-van der Aa syndrome (HVDAS) is an autism spectrum disorder (ASD), accompanied with intellectual disability and facial dysmorphisms. It has been reported that HVDAS is caused by mutations in ADNP, a transcription factor involved in the SWI/SNF remodeling complex.","Congenital malformation"
"H01184","Familial dementia","Familial British dementia (FBD) and familial Danish dementia (FDD) are two autosomal dominant neurodegenerative diseases caused by mutations in the BRI/ ITM2B gene. Familial dementia is characterized by widespread cerebral amyloid angiopathy, parenchymal amyloid deposition, and neurofibrillary tangles.","Neurodegenerative disease"
"H00056","Alzheimer disease","Alzheimer disease (AD) is a chronic disorder that slowly destroys neurons and causes serious cognitive disability. AD is associated with senile plaques and neurofibrillary tangles (NFTs). Amyloid-beta (Abeta), a major component of senile plaques, has various pathological effects on cell and organelle function. To date genetic studies have revealed four genes that may be linked to autosomal dominant or familial early onset AD (FAD). These four genes include: amyloid precursor protein (APP), presenilin 1 (PS1), presenilin 2 (PS2) and apolipoprotein E (ApoE). All mutations associated with APP and PS proteins can lead to an increase in the production of Abeta peptides, specfically the more amyloidogenic form, Abeta42. It was proposed that Abeta form Ca2+ permeable pores and bind to and modulate multiple synaptic proteins, including NMDAR, mGluR5 and VGCC, leading to the overfilling of neurons with calcium ions. Consequently, cellular Ca2+ disruptions will lead to neuronal apoptosis, autophagy deficits, mitochondrial abnormality, defective neurotransmission, impaired synaptic plasticity and neurodegeneration in AD. FAD-linked PS1 mutation downregulates the unfolded protein response and leads to vulnerability to ER stress.","Neurodegenerative disease"
"H00264","Charcot-Marie-Tooth disease","Charcot-Marie-Tooth (CMT) disease, also called hereditary motor and sensory neuropathy (HMSN), is a group of disorders characterized by a chronic motor and sensory polyneuropathy. Based on nerve conduction velocities, the disease can be divided into demyelinating CMT (CMT1), axonal CMT (CMT2) and intermediate CMT. Although more than 70 disease genes for CMT are known, a large number of affected individuals remain without a genetic diagnosis.","Neurodegenerative disease"
"H01719","Optic neuropathy","Optic neuropathy is damage to the optic nerve that causes vision loss frequently. The optic nerve is susceptible to a number of pathologic processes. Causes of the disease include demyelinating, inflammatory, toxic, nutritional, compressive, infiltrative, hereditary, traumatic, and neoplastic. The classic clinical signs of optic neuropathy are visual field defect, dyschromatopsia, and abnormal papillary response. A rapid onset is typical of demyelinating, inflammatory, ischemic, and traumatic causes.","Nervous system disease"
"H01973","Fertile eunuch syndrome","Fertile eunuch syndrome is a form of idiopathic hypogonadotropic hypogonadism in males. It is characterized by eunuchoid features associated with normal or low-normal sized testes, presence of active spermatogenesis despite the absence or scarcity of Leydig cells, and androgenic response (clinical or chemical or both) to administered human chorionic gonadotropin. In this disease, the levels of testosterone and follicle-stimulating hormone (FSH) are inadequate to induce spermatogenesis and the development of secondary sexual characteristics. Mutations in the beta subunit of luteinizing hormone gene have been identified from patients of this disease.","Congenital malformation"
"H01389","Alpers syndrome","Alpers syndrome is a rare mitochondrial disease associated with mutations in the POLG1 gene encoding the mitochondrial DNA polymerase gamma. Alpers syndrome affects children and young adults and is characterized by the clinical triad of refractory seizures, psychomotor regression, and characteristic liver disease. The tempo of disease progression and onset varies among patients. The majority of patients are healthy before disease onset, and seizures herald the disorder in most patients.","Inherited metabolic disease; Mitochondrial disease"
"H01987","Familial dysautonomia","Familial dysautonomia (FD), also known as Riley day syndrome, is an autosomal recessive disorder characterized by developmental arrest in the sensory and autonomic nervous systems. Symptoms include decreased sensitivity to pain and temperature, cardiovascular instability, recurrent pneumonias, and gastrointestinal dysfunction. This disorder is primarily confined to individuals of Ashkenazi Jewish descent, and caused by mutations of the IKAP gene that encodes a scaffolding unit ELP1 for a elongator complex.","Nervous system disease"
"H00855","Triphalangeal thumb-polysyndactyly syndrome","Triphalangeal thumb (TPT) is a rare human hand-foot malformation characterized by a long, finger-like thumb with three phalanges. It can occur either in isolated form or in association with other defects such as triphalangeal thumb-polydactyly syndrome (TPT-PS). TPT is caused by defects in a cis-regulatory sequence ZRS, located in intron 5 of LMBR1, which is crucial for expression of sonic hedgehog (SHH) during limb development.","Congenital malformation"
"H00069","Glycogen storage disease","Glycogen storage disease (GSD) is an autosomal recessive (all types except IXa and IXd) or X-linked (types IXa and IXd) disorder with symptoms ranging from weakness to growth abnormalities. GSD is caused by a defect in an enzyme gene or a transporter gene involved in glycogen metabolism; types I, VII, and XI for processing of glucose, types II-VI and IX for processing of glycogen, and type 0 for glycogen synthesis. Pompe disease (type II) is a lysosomal storage disease.","Inherited metabolic disease"
"H02168","Hypotrichosis-lymphedema-telangiectasia syndrome","Hypotrichosis-lymphedema-telangiectasia syndrome (HLTS) is an extremely rare lymphedema syndrome. The transcription factor SOX18 was shown to play a role in the development of hair, blood vessels and lymphatic vessels. SOX18 mutations are associated with both recessive and dominant HLTS.","Congenital malformation"
"H00263","Acrocallosal syndrome","Acrocallosal syndrome is an autosomal recessive condition, characterized by agenesis of the corpus callosum, polydactyly, minor craniofacial anomalies and psychomotor retardation.","Congenital malformation"
"H01183","Thiamine-responsive megaloblastic anemia","Thiamine-responsive megaloblastic anemia (TRMA), also known as Rogers syndrome, is a rare autosomal recessive inherited disorder characterized by megaloblastic anemia, diabetes mellitus, and progressive sensorineural deafness, due to mutations in SLC19A2, encoding a high-affinity thiamine transporter protein. In addition to the cardinal components, other findings are also reported in TRMA syndrome including congenital heart disease, arrhythmias, cardiomyopathy, retinal degeneration, optic atrophy, situs inversus, aminoaciduria, and stroke.","Inherited metabolic disease"
"H00051","Alveolar soft part sarcoma","Alveolar soft part sarcoma (ASPS) is a rare, histologically distinctive soft-tissue sarcoma typically occurring in children and young adults. Although it displays a relatively indolent clinical course, the ultimate prognosis is poor and is often characterised by late metastases. ASPS is characterised by an unbalanced translocation: der(17)t(X:17)(p11;q25). This translocation causes the fusion of the TEF3 (transcription factor binding to IGHM enhancer 3) with a novel gene at 17q25, named ASPL. Translocation between chromosomes X and 17 is seen in all the tested cases, implicating transcriptional deregulation in the pathogenesis of this tumor.","Cancer"
"H00435","Toxoplasmosis","Toxoplasmosis is a worldwide infection caused by the intracellular parasite Toxoplasma gondii. The majority of horizontal transmissions to humans is caused either by the ingestion of tissue cysts in infected meat or by the ingestion of soil, water, or food contaminated with sporulated oocysts derived from the environment or, less frequently, directly from feline feces. The parasite usually causes asymptomatic infection but in immunocompromised individuals, it can result in fatal disease with encephalitis. Transmission can also occur vertically. Congenital infection causes spontaneous abortion or serious defects such as hydrocephalus, chorioretinitis, and intracranial calcification in infants.","Infectious disease"
"H02362","Benign familial infantile seizure","Benign familial infantile seizure (BFIS) is an autosomal dominant disease characterized by focal seizures, occurring mostly in clusters, and usually first seen between 4 and 8 months of life. Psychomotor development is normal, and seizures usually resolve within the first year of life. PRRT2 has been identified as the major gene found to be mutated in 80 to 90% of cases. Recently, mutations in the genes coding for the voltage-gated sodium channel subunits has been reported.","Nervous system disease"
"H02150","Infantile or early childhood epileptic encephalopathy","Infantile or early childhood epileptic encephalopathy (IECEE) is severe disorder characterized by early-onset epilepsy, severe developmental delay, refractory seizures, and dysmorphic features, and a de novo mutation in PPP3CA. PPP3CA encodes a subunit of calcineurin, a key regulator of synaptic vesicle recycling at nerve terminals. Recently, IECEE caused by mutations in the GABRB2 gene and ATP6V1A gene has also been reported.","Nervous system disease"
"H00607","46,XY gonadal dysgenesis","Gonadal dysgenesis (GD) is a disorder of sex development. Formerly, 46,XY GD was also known as 46,XY sex reversal (SRXY). In 46,XY GD, the gonadal histology can range from fibrous streak gonads to partial GD with presence of testicular tissue. The phenotype of patients with 46,XY GD can vary from normal female to genital ambiguity to an undervirilized male. Mutations involving the testis-determining gene SRY, and other genes involved in sex determination, such as the genes WT1, DHH, NR5A1, SOX9, FOG2/ZFPM2 and MAP3K1 have been identified.","Reproductive system disease"
"H01513","Retinoblastoma","The retinoblastoma is an eye tumor of childhood that arises in the retina and represents the most common intraocular malignancy of infancy and childhood. Tumor formation usually begins with mutation in both alleles of the retinoblastoma tumor suppressor gene RB1, followed by a series of other genetic alterations that correlate with the clinical stage and pathologic findings of the tumor. In retinoblastoma, mutation of RB1 leads to dysfunction or absence of the Rb protein. These mutations promote tumour development by deregulating the E2F family of transcription factors leading to uncontrolled cell cycle progression.","Cancer"
"H02396","Corpus callosum agenesis with facial anomalies and cerebellar ataxia","Corpus callosum agenesis with facial anomalies and cerebellar ataxia (CCAFCA) is a novel autosomal recessive microcephaly intellectual disability syndrome with agenesis of corpus callosum and partial hypoplasia of the vermis and cerebellum. This disease is associated with mutations in FRMD4A, that is involved in cell structure, transport and signaling.","Congenital malformation"
"H01721","Anti-glomerular basement membrane (GBM) disease","Goodpasture syndrome (GS), or anti-glomerular basement membrane (anti-GBM) disease, is a rare and organ-specific autoimmune disease defined by anti-GBM antibody-mediated damage (mainly immunoglobulin G-1) resulting in progressive crescentic glomerulonephritis and, frequently, diffuse pulmonary alveolar hemorrhage. Clinically, GS is characterized by pulmonary hemorrhage and renal failure, although the clinical spectrum may range from only mild symptoms to a relentless and finally lethal outcome. This disease accounts for 10-20% of the patients with acute renal failure following a rapidly progressive glomerulonephritis. The disease is caused by an autoimmune response against the non-collagenase domain of the alpha 3 chain of type IV collagen [alpha3(IV)NC1], found in the glomerular and alveolar basement membranes. Without prompt diagnosis and treatment, the disease can lead to bleeding in the lungs, kidney failure, and even death. Early and intensive treatment with plasmapheresis and immunosuppression with systemic corticosteroids pending results of diagnostic testing, and later cyclophosphamide, is often beneficial, with 90% of patients surviving the acute presentation of GS.","Immune system disease; Kidney disease"
"H01345","Providencia stuartii infection","Providencia is a gram-negative urea-metabolizing bacilli that readily incorporates DNA from other bacteria, enabling it to acquire resistance to a broad spectrum of antibiotics. Providencia stuartii is a bacterium normally found in patients with indwelling urinary catheters, where it causes urinary tract infections. These infections may progress to bacteremia.","Infectious disease"
"H00297","Plague","Plague is a deadly infectious disease caused by Yersinia pestis. The pathogen has rodent reservoirs and is transmitted to humans usually by fleas as vectors. There are three major manifestations: bubonic, septicemic, and pneumonic plagues. Severe epidemics in the past include the Plague of Justinian in the sixth century, the Black Death in the fourteenth century, and the Third Pandemic that began in Central Asia in the nineteenth century. The genome sequences have been determined for the strains responsible for these epidemics.","Infectious disease"
"H00899","Lysinuric protein intolerance","Lysinuric protein intolerance (LPI) is an inherited aminoaciduria caused by defective amino acid transport at the basolateral membrane of epithelial cells in intestine and kidney. Patients affected by this disorder, in general, come to medical attention from early on in life with several significant problems including failure to thrive and intellectual impairment. LPI is caused by mutations in the SLC7A7 gene, which encodes the y+LAT-1 protein, the catalytic light chain subunit of a complex belonging to the heterodimeric amino acid transporter family.","Inherited metabolic disease"
"H01177","Infantile bilateral striatal necrosis","Infantile bilateral striatal necrosis (IBSN) is a neurological disorder characterized by symmetrical degeneration of the caudate nucleus, putamen, and occasionally the globus pallidus, with little involvement of the rest of the brain. The clinical features of IBSN include developmental regression, choreoathetosis, dystonia, spasticity, dysphagia, failure to thrive, nystagmus, optic atrophy, and mental retardation. The mechanism of IBSN has not been elucidated, although it has been reported that IBSN usually occurs as a result of metabolic, familial, or toxic diseases. Mutations in the adenosine triphosphatase 6 gene (complex V) have been described in families with mitochondrial inheritance, while there is much evidence that supports the role of the mutation in NUP62 as the cause of autosomal recessive IBSN. Human herpes virus-6 (HHV-6) infection has been reported to associated with this disease.","Nervous system disease"
"H00638","Ectrodactyly-ectodermal dysplasia cleft-palate syndrome","Ectrodactyly-ectodermal dysplasia-cleft lip/palate (EEC) syndrome is a rare autosomal dominant genetic disorder. This condition is a combination of ectrodactyly, the lobster claw-like deformities of the hands and feet, ectodermal dysplasia affecting skin, hair, and nails, and cleft lip with or without cleft palate. Other symptoms include anomalies of eyes and urinary tract.","Congenital malformation"
"H01980","SCAD deficiency","Short-chain acyl-CoA dehydrogenase (SCAD) deficiency is a rare mitochondrial fatty acid oxidation disorder, caused by mutations in the ACADS gene. The clinical features range from hypoglycemia and vomiting to hypotonia and seizures accompanied with developmental delay.","Inherited metabolic disease; Mitochondrial disease"
"H00852","Klippel-Feil syndrome","Klippel-Feil syndrome (KFS) is a rare disorder characterized by congenital fusion of two or more cervical vertebrae. Scoliosis, mirror movements, otolaryngological, kidney, ocular, cranial, limb, and/or digit anomalies are often associated. It has been reported that KFS is caused by mutations in the GDF6 or GDF3 genes in an autosomal dominant manner. KFS is also inherited in an autosomal recessive manner. Recently, involved genes (MEOX1 and MYO18B) have been identified.","Congenital malformation"
"H01974","Limb-girdle muscular dystrophy 2B","Limb-girdle muscular dystrophy type 2B (LGMD2B) is an autosomal recessive phenotype of dysferlinopathies, muscle disorders caused by mutations in the dysferlin gene (DYSF). Clinically, it is characterized by weakness in the proximal muscles at onset, involving predominantly the lower limbs. At late stages of the disease, loss of muscle bulk in the pelvic girdle and calf may appear. Onset is typically in the late teens or early adulthood.","Nervous system disease; Musculoskeletal disease"
"H01148","Caulobacter infection","The genus Caulobacter is a gram-negative bacteria characterized by asymmetric cell division and stalk. Although infection with Caulobacter species is rare, a case has been reported in a patient undergoing intermittent peritoneal dialysis.","Infectious disease"
"H02309","Adenosine deaminase deficiency","Adenosine deaminase (ADA) deficiency causes severe combined immunodeficiency disease (SCID). Profound lymphopenia in this disorder has been attributed to toxic levels of ADA substrates, particularly deoxyadenosine, generated from nucleic acid breakdown associated with cell turnover in marrow, thymus, and lymph nodes. Most patients have SCID, which is usually diagnosed in infancy and is often fatal, but some patients are diagnosed later in childhood or as adults. More than 50 ADA mutations are known. Most patients are heteroallelic, and most alleles are rare.","Immune system disease"
"H00208","Hyperbilirubinemia","Gilbert disease and Crigler-Najjar syndromes result in unconjugated hyperbilirubinemia caused by deficiency of bilirubin-UDP-glucuronosyltransferase which is involved in the detoxification of bilirubin by conjugation with glucuronic acid. Gilbert disease is a benign familial disorder characterized by low-grade chronic hyperbilirubinemia, while Crigler-Najjar syndromes are more severe by kernicterus and jaundice. Dubin-Johnson syndrome (DJS) is caused by mutations in ABCC2, a canalicular bilirubin glucuronide and xenobiotic export pump. Rotor syndrome (RS) is caused by mutations in the SLCO1B1 and SLCO1B3 genes that encode organic anion transporters. In both DJS and RS, mild jaundice begins shortly after birth or in childhood. There are no signs of hemolysis, and routine hematologic and clinical-biochemistry test results are normal, aside from the primarily conjugated hyperbilirubinemia. The hepatocyte pigment deposits is typical of DJS. Total urinary excretion of coproporphyrins is greatly increased in RS.","Congenital disorder of metabolism"
"H00806","Benign familial neonatal seizure","Benign familial neonatal seizure (BFNS) is a benign epilepsy syndromes with autosomal dominant inheritance. They are a group of epilepsies which have a primary genetic background, usually no structural brain abnormalities and most of them have a benign course without additional neurological symptoms. BFNS are caused by loss-of-function mutations in the two genes KCNQ2 and KCNQ3 encoding the voltage-gated K+ channels.","Nervous system disease"
"H01920","Partington syndrome","Partington syndrome, also known as Partington X-linked mental retardation syndrome (PRTS), is characterized by moderate to severe mental retardation, dysarthria, facial muscle weakness, severe dysdiadochokinesis, slow dystonic movements, and mild spasticity of the hands. The symptoms are extrapyramidal and without cerebellar involvement. ARX gene mutations were reported in various forms of X-linked mental retardation, including Partington syndrome. ARX is considered to have an important role in neuronal proliferation, interneuronal migration and differentiation in the embryonic brain, and also in the differentiation of the testis. Expansion of polyalanine tracts, missense mutation outside the homeodomain and deletions of exon 5 cause non-malformation syndromes such as Partington syndrome.","Nervous system disease"
"H01578","Subacute myelo-optico-neuropathy (SMON)","Subacute myelo-optico-neuropathy (SMON) is a severe neurodegenerative disorder caused by poisoning due to over-dose and prolonged oral administration of clioquinol. SMON is characterized by subacute onset of sensory and motor disorders in the lower half of the body and visual impairment preceded by abdominal symptoms, such as abdominal pain and diarrhea. Despite clinical features mimicking infection or multiple sclerosis, the discovery of the green hairy tongue and the green urine in SMON patients aroused researchers' interest and thereby began solving the cause of SMON. The green color was derived from a chelate compound of clioquinol with ferric iron. A large number of SMON were observed throughout Japan, and the total number of cases reached nearly 10,000 by 1970. After the governmental ban on the use of clioquinol in September 1970, there was a dramatic disappearance of new case of SMON. However, in Japan, there are still more than 2500 SMON patients suffering from severe dysesthesia/paresthesia and ataxic paraplegia.","Neurodegenerative disease"
"H00698","Nemaline myopathy","Nemaline myopathy (NM) is the most common congenital myopathy inherited in an autosomal dominant or autosomal recessive manner. It is characterized by the presence of rods or nemaline bodies, which are red-purple inclusions in myofibers detected by modified Gomori trichrome technique. The hallmark symptoms are generalized muscle weakness with facial involvement or predominant involvement of proximal limb and respiratory muscles. Currently, NM is classified into six different forms: severe congenital (neonatal) form; Amish NM, intermediate congenital form; typical congenital form; childhood-onset form; and adult-onset (late-onset) form. Mutations in several genes, encoding components of the sarcomeric thin filaments, have been identified. Mutations in ACTA1 and NEB nebulin are the most common.","Nervous system disease; Musculoskeletal disease"
"H00005","Chronic lymphocytic leukemia","Chronic lymphocytic leukemia (CLL) is caused by the abnormal progressive accumulation of functionally incompetent monoclonal B-lymphocytes in blood, bone marrow, lymph nodes and spleen. It is the most common adult leukemia in Western countries, accounting for about 30% of total leukaemias. Worldwide there are approximately 180,000 new cases every year. A main focus in CLL research involved the evaluation of genetic features related to somatic gene mutation or deletions that disrupt apoptosis and enhance tumor cell proliferation. The best characterized genes are TP53 (also known as p53) and ATM, for which mutations and/or deletions have been described that predict rapid disease progression, resistance to conventional therapies and poor survival.","Cancer"
"H00839","Porencephaly","Porencephaly is a rare disease of central nervous system characterized by the existence of degenerative cavities filled with cerebrospinal fluid in the brain. It is probably caused by perinatal intracerebral hemorrhages.","Congenital malformation"
"H00237","Diamond-Blackfan anemia","Diamond-Blackfan anemia (DBA) is a genetically and clinically heterogeneous congenital erythroid aplasia that develops within the first year of life. Faulty ribosome biogenesis is hypothesized to be the underlying defect, leading to erythroid failure due to accelerated apoptosis in affected erythroid progenitors/precursors.","Ribosomopathy"
"H00653","Marfan syndrome","Marfan syndrome (MFS) is a relatively common autosomal dominant disorder of connective tissue. It affects many parts of the body involving the skeletal, ocular, and cardiovascular systems. Cardiac manifestations are significant contributors to morbidity and mortality. MFS is caused by mutations in the gene for fibrillin-1.","Congenital malformation"
"H01781","Autophagic vacuolar myopathy","Autophagic vacuolar myopathies (AVM) are a group of disorders united by shared histopathological features on muscle biopsy that include the aberrant accumulation of autophagic vacuoles. They are characterized by autophagic vacuoles in which the vacuolar membranes have sarcolemmal features, and include four entities: Danon disease, X-linked myopathy with excessive autophagy (XMEA), infantile AVM, and adult onset AVM with multiorgan involvement. Danon disease has been shown to be associated with mutations in the LAMP2 gene located on the X chromosome. XMEA is characterized by weakness and wasting primarily of the proximal muscles of the lower extremities. Mutations in the VMA21 gene at Xq28 cause XMEA by reducing the activity of lysosomal hydrolases.","Nervous system disease; Musculoskeletal disease"
"H02104","Megalocornea","Megalocornea (MGC1) is a rare congenital disease of the anterior eye segment characterized by bilateral enlarged corneas with a horizontal diameter of 13 mm or more (measured after the age of two years) and reduced central corneal thickness in the absence of raised intraocular pressure (IOP). It is an important differential diagnosis for primary congenital glaucoma (PCG) [DS:H01203] that leads to a high risk of vision loss and needs a fast diagnostic clarification and prompt treatment. Furthermore, MGC1 is classified as non-syndromic and has to be distinguished from megalocornea in the context of syndromes, e.g. neonatal Marfan syndrome [DS:H00653] or megalocornea-mental-retardation (MMR) syndrome. MGC1 has been reported to be caused by mutations in the CHRDL1 gene on Xq23.","Nervous system disease"
"H02336","Deafness, Y-linked","Hearing loss is the most common sensory disorder in humans. Hereditary hearing loss (HHL) contributes to more than 60% of deafness cases, with autosomal dominant, recessive, and X-linked forms. Although Y-linked deafness is unusual and extremely rare, missense mutations in the TBL1Y gene has been found in families affected by HHL.","Nervous system disease"
"H00461","Ischiocoxopodopatellar syndrome","Ischiocoxopodopatellar syndrome, also known as small patella syndrome, is a skeletal dysplasia with anomalies of the pelvis. Ossification of the ischia and inferior pubic rami is also disrupted in patients.","Congenital malformation"
"H01775","PCDH19-related epilepsy syndrome","PCDH19-related epilepsy syndrome is a disorder characterized by the recurrence of seizures during infancy, which is often combined with intellectual disability or autistic features manifested exclusively in females. This disorder, first reported as epilepsy and mental retardation limited to females (EMFR) and recently renamed early infantile epileptic encephalopathy 9 (EIEE9). It was transmitted via asymptomatic males, suggesting an unusual X-linked inheritance with selective involvement of females. Mutations in the X-chromosome-encoded protocadherin 19 (PCDH19) cause this disorder, and are confirmatory for the diagnosis.","Nervous system disease"
"H00495","Eiken dysplasia","Eiken dysplasia is an extremely rare form of multiple epiphyseal dysplasia It is caused by a homozygous nonsense mutation in the PTHR1 gene.","Congenital malformation"
"H01547","Venezuelan equine encephalitis","Venezuelan equine encephalitis is an infection of the central nervous system caused by Venezuelan equine encephalitis virus (VEEV), an alphavirus in the Togaviridae family of +ssRNA viruses, and transmitted by Ochlerotatus mosquitoes. VEEV was first isolated in 1938 in Venezuela.","Infectious disease"
"H01123","HMG-CoA synthase deficiency","HMG-CoA synthase (HMGCS) deficiency is a autosomal recessive disorder of ketogenesis. Two isoforms of HMGCS are found in higher eukaryotes: the cytosolic HMGCS1 and mitochondrial HMGCS2. Mitochondrial HMGCS2 is involved in hepatic ketogenesis, and HMGCS2 deficiency causes hypoketotic hypoglycaemia after prolonged fasting. To date, no mutations have been identified in the human cytosolic HMGCS1.","Inherited metabolic disease; Mitochondrial disease"
"H01311","Enteroinvasive Escherichia coli (EIEC) infection","Enteroinvasive Escherichia coli (EIEC) infection is common in developing countries and comparatively rare in developed countries. EIEC invades intestinal epithelial cells, causing necrosis, ulceration of the mucous membrane, resulting in a dysentery-like syndrome with fever and mucous-bloody stools. EIEC strains contain a large invasion-associated plasmid, which are nearly identical to those of Shigella species.","Infectious disease"
"H01927","Van der Woude syndrome","Van der Woude syndrome (VWS), the most frequent form of syndromic clefting, is a rare developmental, congenital malformation with autosomal dominant inheritance, high penetrance, and variable expressivity. Clinical manifestation includes bilateral midline lower lip pits, cleft lip, and cleft palate along with hypodontia. The other associated features of VWS which may or may not be present are hypoplasia, ankyloglossia, high arched palate, limb anomalies, congenital heart defects, and so forth. Popliteal pterygium syndrome (PPS) is an allelic syndrome of VWS. These syndromes emanate mainly from etiologic variants in IRF6 gene, though GRHL3 has been shown to be mutated in about 5% of VWS patients that lack etiologic variants in IRF6. Etiologic IRF6 variants account for over 70% of cases of VWS. The treatment of VWS patients includes all necessary surgical and multidisciplinary procedures for the correction of serious anomalies including clefts.","Developmental disorder"
"H01329","Paracoccidioidomycosis","Paracoccidioidomycosis is a systemic endemic mycosis caused by Paracoccidioides brasiliensis and Paracoccidioides lutzii, exhibiting geographically restricted distribution from southern Mexico to northern Argentina. Its natural habitat is primarily the soil and the infection is caused by intense and continued contact with the soil. It can affect any organ in the body, but it is primarily involved in the lungs and potentially disseminates to other organs, mainly mucosa and skin.","Infectious disease"
"H00801","Familial thoracic aortic aneurysm and dissection","Thoracic aortic aneurysms leading to acute aortic dissections (TAAD) are the major diseases that affect the thoracic aorta. While majority of the cases are sporadic, more than 20% are inherited as a single gene disorder. Familial TAAD is diagnosed based on the presence of dilatation and/or dissection of the thoracic aorta, absence of clinical features of Marfan syndrome, Loeys-Dietz syndrome, or vascular Ehlers-Danlos syndrome, and presence of a positive family history of TAAD. TGFBR2, TGFBR1, MYH11, ACTA2, and two loci on other chromosomes, AAT1 and AAT2, are associated with familial TAAD.","Cardiovascular disease"
"H00459","Synpolydactyly","Synpolydactyly (SPD) is a dominantly inherited congenital limb malformation showing digit duplication and webbing of third and fourth fingers. Mutation in HOXD13 induces synpolydactyly. Synpolydactyly 2 is associated with metacarpal and metatarsal synostoses. Synpolydactyly 2 is very rare and caused by mutations in FBLN1.","Congenital malformation"
"H01316","Dermatophytosis","Dermatophytosis (tinea, ringworm) is an infection of keratinized structures, such as the hair, skin or nails caused by dermatophyte fungi of the genera Trichophyton, Epidermophyton or Microsporum. Tinea capitis, tinea pedis and onychomycosis are common dermatologic diseases that may result from such an infection. Dermatophytes are transmitted by direct contact with infected individuals, animals and soil or by indirect contact with contaminated fomites.","Infectious disease"
"H01124","Pyridoxamine-5'-phosphate oxidase (PNPO) deficiency","Pyridoxamine-5'-phosphate oxidase (PNPO) deficiency is a rare autosomal recessive disorder that causes intractable seizures that are not responsive to anticonvulsant drugs and pyridoxine. Patients with this deficiency have very low concentrations of pyridoxal 5'-phosphate (PLP), leaving exogenous pyridoxal/PLP as the only source of the active cofactor. Clinically, this disease presents with neonatal epileptic encephalopathy with severe seizures which do not respond to anticonvulsant drugs or pyridoxine but shows a dramatic response to PLP. Pathogenic mutations in PNPO gene have been identified.","Nervous system disease"
"H01918","Familial autosomal recessive hypercholesterolemia","Autosomal recessive hypercholesterolemia (ARH) is a rare disorder characterized by elevated low-density lipoprotein (LDL) serum levels, xanthomatosis, and premature coronary artery disease. Several dyslipidemias have been identified which lead to severe primary hypercholesterolemia. Among them, ARH is characterized by clinical symptoms and plasma cholesterol levels intermediate between those found in heterozygous and homozygous familial hypercholesterolemia (FH) [DS:H00155] individuals. ARH patients develop symptomatic coronary artery disease later in life and their xanthomas tend to be large and bulky. In 2001, ARH was found to be caused by mutations in the LDL receptor adaptor protein 1 (LDLRAP1). In ARH, the internalization of the ligand-receptor complex cannot occur and all the LDL receptors accumulate on the cell membrane. In general, ARH patients show a better response to lipid-lowering therapy than the FH patients, and they rarely require LDL apheresis.","Inherited metabolic disease; Cardiovascular disease"
"H00492","SHOX-related short stature","Isolated short stature, Leri-Weill and Langer syndromes are conditions with growth retardation. Patients also exhibit mesomelic shortening in Leri-Weill and Langer syndromes. These conditions are due to mutations in SHOX gene within the pseudoautosomal regions of sex chromosomes.","Congenital malformation"
"H01540","Chikungunya fever","Chikungunya fever is an infectious disease caused by Chikungunya virus (CHIKV), an alphavirus in the Togaviridae family of +ssRNA viruses, and transmitted by Aedes mosquitoes. CHIKV was first recognized as a human pathogen during the 1950s in Africa, but it may have caused outbreaks from as early as the 1700s.","Infectious disease"
"H01772","Adrenal hypoplasia, congenital","Adrenal hypoplasia congenital (AHC) is an inherited disorder of the adrenal cortex commonly manifested as an early onset adrenal insufficiency syndrome. AHC includes X-linked form, a rare autosomal recessive form [DS:H02316], and IMAGE syndrome [DS:H02319]. If untreated, adrenal insufficiency is rapidly lethal as a result of hyperkalemia, acidosis, hypoglycemia, and shock. A constant feature of the X-linked AHC is the association with hypogonadotropic hypogonadism (HHG). Affected males typically have delayed puberty or arrested puberty caused by HHG. Mutations in the DAX-1 (NR0B1) gene are responsible for X-linked AHC.","Endocrine and metabolic disease"
"H02331","Gastrointestinal defects and immunodeficiency syndrome","Gastrointestinal defects and immunodeficiency syndrome (GIDID) is a rare hereditary disease characterized by intestinal obstructions and profound immune defects. It has been suggested that TTC7A gene defects cause this disease.","Congenital malformation"
"H00466","Grebe dysplasia","Acromesomelic dysplasia is a rare form of severe acromesomelic limb shortening inherited in autosomal recessive fashion. Lower limbs are more affected than the upper limbs, showing nonfunctional fingers. Homozygous mutations in GDF5 are the cause of the disease.","Congenital malformation"
"H00654","Barth syndrome","Barth syndrome is a rare X-linked recessive disorder of infancy characterized by myopathy, cardiomyopathy, cyclic neutropenia, short stature, low cholesterol, and mitochondrial abnormalities. Barth syndrome is due to mutations in the TAZ gene, the exact function of which is unknown but there are indications that it is directly involved in the metabolism of cardiolipin localized in the inner mitochondrial membrane.","Inherited metabolic disease"
"H01786","Congenitally corrected transposition of the great arteries","Congenitally corrected transposition of the great arteries is a rare cardiac defect characterized by characterised by the combination of atrioventricular (AV) discordance and ventriculo-arterial (VA) discordance. The morphologic left ventricle and mitral valve supply the pulmonary circulation and the morphologic right ventricle and tricuspid valve supply the systemic circulation. The anatomy is described as congenitally 'corrected' because the flow of blood is normal with the deoxygenated systemic venous blood being pumped to the lungs and the well oxygenated pulmonary venous blood being pumped to the body. More than 90% of patients have additional anatomical abnormalities. The most frequent are ventricular septal defects, left ventricular outflow tract obstruction, and abnormalities of the tricuspid valve.","Developmental disorder; Cardiovascular disease"
"H02103","DeSanto-Shinawi syndrome","DeSanto-Shinawi syndrome is characterised by facial dysmorphism, eye abnormalities, developmental delay, behavioral abnormalities, and hypotonia. Recent case reports of patients have implicated overlapping deletions encompassing 10p11.23 in the specific features of this disease. And it has been suggested that WAC loss-of-function mutations are responsible for most of those phenotypic features.","Chromosomal abnormality"
"H00230","Hereditary spherocytosis","Hereditary spherocytosis (SPH) is a heterogeneous group of disorders characterized by rounded red cells and chronic hemolysis.","Hematologic disease"
"H00002","T-cell acute lymphoblastic leukemia","Acute lymphocytic leukemia (ALL) is a clonal stem cell malignancy of excessive lymphoblast proliferation. It is now understood that ALL and lymphoblastic lymphoma are the same disease entities at the morphologic and immunophenotypic levels and classified as either B- and T-cell lymphoblastic leukemia/lymphoma (B-ALL and T-ALL). T-ALL comprises 15% of paediatric and 25% of adult ALL cases. T cell transformation is a multi-step process in which different genetic alterations cooperate to alter the normal mechanisms that control cell growth, proliferation, survival, and differentiation during thymocyte development. In this context, constitutive activation of NOTCH1 signaling is the most prominent oncogenic pathway in T cell transformation. In addition, T-ALLs characteristically show the translocation and aberrant expression of transcription factor oncogenes. These oncogenic transcription factors include T-cell leukaemia homeobox protein 1 (TLX1 also known as HOX11), TLX3 (HOX11L2), LYL1, TAL1 and MLL.","Cancer"
"H01911","Syndromic autosomal recessive mental retardation","Mental retardation (MR) is a neurodevelopmental disorder characterized by low intelligence quotient (IQ) and deficits in adaptive behaviors. To date, several genes have been identified for autosomal recessive mental retardation (ARMR). These genes have a variety of functions and participate in multiple biochemical pathways. ARMR is subdivided into syndromic and non-syndromic forms, depending on whether further abnormalities are found or not. Syndromic ARMR is characterized by recognizable dysmorphic features, neurological complications, and/or metabolic abnormalities.","Mental and behavioural disorder"
"H01549","Rift Valley fever","Rift Valley fever is an infectious disease caused by Rift Valley fever virus (RVFV), a phlebovirus in the order Bunyavirales of -ssRNA viruses, and transmitted by Aedes and Culex mosquitoes. RVFV was first isolated in 1931 in Kenya.","Infectious disease"
"H02338","PEHO-like syndrome","PEHO syndrome [DS:H02252] is a rare hereditary disease comprising severe retardation, early onset epileptic seizures, optic nerve/cerebellar atrophy, pedal oedema, and early death. Cases lacking either optic atrophy or cerebellar hypoplasia are often termed PEHO-like syndrome. A homozygous frameshift mutation in CCDC88A has been identified in affected individuals.","Nervous system disease"
"H00837","Leber congenital amaurosis","Leber congenital amaurosis (LCA) is a heterogeneous group of severe retinal degenerations, which typically becomes evident in the first year of life. Affected infants have little or no retinal photoreceptor function as tested by electroretinography. LCA is generally inherited in an autosomal recessive manner, and caused by mutations in more than a dozen genes. Several have been demonstrated as potentially efficacious gene therapy targets.","Nervous system disease"
"H00239","Bartter syndrome","Bartter syndrome (BARTS) is a heterogeneous rare disease unified by autosomal recessive transmission. BS is characterized by impaired salt reabsorption in the thick ascending loop of Henle with elevated aldosterone excretion resulting in salt wasting, hypokalemic metabolic alkalosis, and hypercalciuria. Type 1 and 2 are the neonatal type but genetically, clinically, and biochemically different. Type 4A shows Bartter syndrome with sensorineural deafness. Type 3 is classic Bartter syndrome. Autosomal dominant hypocalcemia with Bartter syndrome (HYPOC1) is characterized by hypocalcemic hypercalciuria with parathyroid hormone suppression.","Endocrine and metabolic disease"
"H01576","Spondyloenchondrodysplasia with immune dysregulation (SPENCDI)","Spondyloenchondrodysplasia with immune dysregulation (SPENCDI) is an autosomal recessive skeletal dysplasia, characterised by radiolucent metaphyseal and vertebral lesions. Patients may exhibit varying degrees of neurological impairment including spasticity, developmental delay, and basal ganglia calcification. In addition, signs of autoimmune disease resembling systemic lupus erythematosus (SLE) are commonly observed. Furthermore, patients may also suffer from recurrent infections. SPENCD is caused by biallelic mutations in ACP5, encoding tartrate-resistant acid phosphatase (TRAP). Affected individuals displayed an absence of TRAP serum expression and, in keeping with autoimmune manifestations, increased levels of serum interferon-alpha (IFNalpha) and an upregulation of interferon-stimulated genes (ISGs).","Immune system disease; Musculoskeletal disease"
"H01744","Autoinflammatory syndrome with pyogenic bacterial infection and amylopectinosis","Autoinflammatory syndrome with pyogenic bacterial infection and amylopectinosis is a rare autosomal recessive disorder characterized by chronic autoinflammation, invasive bacterial infections, and muscular amylopectinosis. Patients carried biallelic loss-of-expression and loss-of-function mutations in HOIL1 (RBCK1) gene coding for a component of the linear ubiquitination chain assembly complex (LUBAC). The patients developed recurrent episodes of fever and systemic inflammation with higher concentrations of acute-phase markers, hepatosplenomegaly and lymphadenopathy very early in life. These features are commonly seen in the primary autoinflammatory diseases, although these HOIL-1-deficient patients failed to develop other cardinal features of the primary autoinflammatory diseases, such as pleuritis, pericarditis, peritonitis, or neutrophilic dermatoses.","Immune system disease"
"H00696","Haim-Munk syndrome","Haim-Munk syndrome is a rare autosomal recessive disorder of keratinization characterized by palmoplantar hyperkeratosis and marked periodontitis. Additional features include onychogryphosis, arachnodactyly, nail dysplasia, pes planus, and acroosteolysis. Mutations in cathepsin C gene cause this disease.","Congenital malformation"
"H01320","Epidemic keratoconjunctivitis","Epidemic keratoconjunctivitis (EKC) is a highly contagious and severe form of eye disease caused by human adenoviruses (HAdVs). There are two well-defined adenoviral keratoconjunctivitis clinical syndromes: EKC and pharyngoconjunctival fever (PCF) [DS:H01420], which are caused by different HAdV serotypes. HAdV-8, HAdV-19, and HAdV-37 are common causative agents of EKC. In addition to these above-mentioned types, HAdV-3, HAdV-4, HAdV-7, HAdV-9, HAdV-15, HAdV-53, and HAdV-54 have also been identified as causative agents of EKC. However, HAV-8 is responsible for the highest number of EKC cases worldwide and is associated with severe clinical manifestations. EKC patients may complain about influenza-like symptoms, including fever, malaise, respiratory symptoms, nausea, vomiting, diarrhea, and myalgia. The incubation period is 2-14 days, and the person may remain infectious for 10-14 days after the onset of the symptoms. Symptoms tend to last for 7-21 days.","Infectious disease"
"H01112","Polyhydramnios, megalencephaly, and symptomatic epilepsy","Polyhydramnios, megalencephaly, symptomatic epilepsy (PMSE) is a severe human developmental and epileptic syndrome caused by a homozygous partial deletion in the STRAD-alpha gene (LYK5), truncating 180 C-terminal residues of the protein. Individuals affected by this condition suffer from severe mental retardation, gross movement disorders, and childhood mortality. Severe intractable epilepsy and megalencephaly are characteristic.","Congenital malformation"
"H00206","Mevalonate kinase deficiency","Mevalonate kinase deficiency is an autosomal recessive disorder, which is identified as the cause of two inherited human autoinflammatory disorders: mevalonic aciduria (MVA) and hyperimmunoglobulinemia D syndrome (HIDS). Mevalonate kinase is located at the beginning of the cholesterol biosynthesis pathway compromising the biosynthesis of nonsterol isoprenes in addition to cholesterol. Patients of MVA show the symptoms, including dysmorphic features, cataracts, neurologic symptoms. The majority of patients with HIDS experience only recurrent febrile crises, without any neurologic abnormalities or dysmorphic features. Mevalonic kinase activity in HIDS patients is generally in the range of 5-15% of normal as compared to 0-4% in MVA.","Inherited metabolic disease; Immune system disease"
"H00034","Carcinoid","Carcinoid tumors are relatively uncommon neoplasms that nonetheless comprise up to 85% of neuroendocrine gastrointestinal neoplasms. They most frequently occur in the midgut and develop from neuroendocrine cells that are normally and diffusely present in this location. Most carcinoids are sporadic but epidemiological studies report a familial risk. Moreover, carcinoids can occur within the multiple endocrine neoplasia (MEN) syndrome, a rare familiar tumor syndrome in which mutations in the MEN1 gene are manifested. Recently, it has been shown that a majority (78%) of sporadic carcinoids display loss of heterozygosity for markers around the MEN 1 region, thus suggesting involvement of this gene in the pathogenesis of both familial and sporadic carcinoids.","Cancer"
"H00808","Idiopathic generalized epilepsies","Idiopathic generalized epilepsies (EIG) are the most common types of epilepsy in childhood and adolescence. Based on the main seizure type and age at onset, four classic subsyndromes exist: childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy, and epilepsy with generalized tonic-clonic seizures alone. Although autosomal dominant inheritance occurs in rare families, clinical genetic data indicate that complex inheritance involving two or more genes is likely in the majority of families.","Nervous system disease"
"H01582","Pellagra","Pellagra is a remarkable chronic wasting disorder, the late stage of a severe cellular deficiency of niacin (vitamin B3). The classical triad of pellagra is dermatitis, diarrhea and dementia. Early symptoms include lassitude, weakness, loss of appetite, mild digestive disturbances and psychiatric distress. The dermatitis caused by pellagra is a bilaterally symmetrical eruption at cutaneous sites of solar exposure. It tends to be painful to touch during the acute phase and can eventually become so clinically striking that the patient may become ostracized. Untreated pellagra results in death from multiorgan failure. Pellagra used to be a disease of epidemic proportions in the developed world. In the 18th century, it was linked with poverty and subsistence on nutritionally marginal corn-based diets. In the 1940s and 1950s, with expanded biochemical knowledge, pellagra was reformulated as a deficiency disease due to inadequate niacin and its amino acid precursor tryptophan. It is currently seen in association with other co

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