name: hereditary sclerosing poikiloderma with tendon and pulmonary involvement

description: Hereditary fibrosing poikiloderma-tendon contractures-myopathy-pulmonary fibrosis syndrome is a rare, genetic, hereditary poikiloderma syndrome characterized by early-onset poikiloderma (mainly on the face), hypotrichosis, hypohidrosis, muscle and tendon contractures with varus foot deformity, progressive proximal and distal muscle weakness in all extremities, and progressive pulmonary fibrosis. Mild lymphedema of the extremities, growth retardation, liver impairment, exocrine pancreatic insufficiency and hematologic abnormalities are additional variable features.


retinitis pigmentosa 28

category: biolink:Disease biolink:DiseaseOrPhenotypicFeature biolink:BiologicalEntity biolink:ThingWithTaxon biolink:NamedThing

description: Any retinitis pigmentosa in which the cause of the disease is a mutation in the FAM161A gene.


factor XIII, A subunit, deficiency of

description: Deficiency of factor XIII subunit A, leading to a reduced factor XIII activity. Activated Factor XIII cross-links fibrin polymers solidifying the clot.


factor XIII, b subunit, deficiency of

description: Deficiency of factor XIII subunit B, leading to a reduced factor XIII activity. Activated Factor XIII cross-links fibrin polymers solidifying the clot.


Charcot-Marie-Tooth disease type 4E

description: Charcot-Marie-Tooth disease type 4E (CMT4E) is a congenital, hypomyelinating subtype of Charcot-Marie-Tooth disease type 4 characterized by a Dejerine-Sottas syndrome-like phenotype (incl. hypotonia and/or delayed motor development in infancy), extremely slow nerve conduction velocities, potential respiratory dysfunction, cranial nerve involvement, and the typical CMT phenotype, i.e. distal muscle weakness and atrophy, sensory loss, and foot deformity.


Charcot-Marie-Tooth disease type 1D

description: A form of CMT1, caused by mutations in the EGR2 gene (10q21.1), with a variable severity and age of onset (from infancy to adulthood), that usually presents with gait abnormalities, progressive wasting and weakness of distal limb muscles, with possible later involvement of proximal muscles, foot deformity and severe reduction in nerve conduction velocity. Additional features may include scoliosis, cranial nerve deficits such as diplopia, and bilateral vocal cord paresis.


name: autosomal recessive nonsyndromic hearing loss 88

description: Any autosomal recessive nonsyndromic deafness in which the cause of the disease is a mutation in the ELMOD3 gene.


hereditary spastic paraplegia 64

description: An extremely rare and complex form of hereditary spastic paraplegia (see this term), reported in only 4 patients from 2 families to date, characterized by spastic paraplegia (presenting between the ages of 1 to 4 years with abnormal gait) associated with microcephaly, amyotrophy, cerebellar signs (e.g. dysarthria) aggressiveness, delayed puberty and mild to moderate intellectual disability. SPG64 is due to mutations in the ENTPD1 gene (10q24.1), encoding ectonucleoside triphosphate diphosphohydrolase 1.


ethylmalonic encephalopathy

description: Ethylmalonic acid encephalopathy (EE) is defined by elevated excretion of ethylmalonic acid (EMA) with recurrent petechiae, orthostatic acrocyanosis and chronic diarrhea associated with neurodevelopmental delay, psychomotor regression and hypotonia with brain magnetic resonance imaging (MRI) abnormalities.


name: GRN-related frontotemporal lobar degeneration with Tdp43 inclusions

description: A frontotemporal dementia characterized by variable phenotypic expression typically including social, behavioral, or language deterioration, rather than memory or motor deficits and the presence of TARDBP-positive inclusions that has material basis in mutation in the GRN gene on chromosome 17q21.31.


neuronal ceroid lipofuscinosis 11

description: Any neuronal ceroid lipofuscinosis in which the cause of the disease is a mutation in the GRN gene.


trichorhinophalangeal syndrome type II

description: Langer-Giedon syndrome, also known as trichorhinophalangeal syndrome type 2, is a very rare, genetic, multiple congenital anomaly disorder characterized by bone abnormalities, distinctive facial features, multiple exostoses, and intellectual disability.


chondrosarcoma

description: A malignant cartilaginous matrix-producing mesenchymal neoplasm arising from the bone and soft tissue. It usually affects middle-aged to elderly adults. The pelvic bones, ribs, shoulder girdle, and long bones are the most common sites of involvement. Most chondrosarcomas arise de novo, but some may develop in a preexisting benign cartilaginous lesion.


name: intellectual disability, autosomal recessive 58

description: Any autosomal recessive non-syndromic intellectual disability in which the cause of the disease is a mutation in the ELP2 gene.


cutis laxa, autosomal dominant 1

description: Any autosomal dominant cutis laxa in which the cause of the disease is a mutation in the ELN gene.


supravalvular aortic stenosis

description: SupraValvar Aortic Stenosis (SVAS) is characterized by the narrowing of the aorta lumen (close to its origin) or other arteries (branch pulmonary arteries, coronary arteries). This narrowing of the aorta or pulmonary branches may impede blood flow, resulting in heart murmur and ventricular hypertrophy (in case of aorta involvement). The narrowing results from a thickening of the artery wall, which is not related to atherosclerosis.


name: myeloproliferative disorder, chronic, with eosinophilia


acute myeloid leukemia

description: Acute myeloid leukemia (AML) is a group of neoplasms arising from precursor cells committed to the myeloid cell-line differentiation. All of them are characterized by clonal expansion of myeloid blasts. AML manifests by fever, pallor, anemia, hemorrhages and recurrent infections.


otofaciocervical syndrome 1

description: Any otofaciocervical syndrome in which the cause of the disease is a mutation in the EYA1 gene.


branchiootic syndrome 1

description: Any branchiootic syndrome in which the cause of the disease is a mutation in the EYA1 gene.


name: epidermolysis bullosa simplex 4, localized or generalized intermediate, autosomal recessive


Weaver syndrome

description: Weaver syndrome (WVS) is a rare, multisystem disorder characterized by tall stature, a typical facial appearance (hypertelorism, retrognathia) and variable intellectual disability. Additional features may include camptodactyly, soft doughy skin, umbilical hernia, and a low hoarse cry.


hemophilia B

description: Hemophilia B is a form of hemophilia characterized by spontaneous or prolonged hemorrhages due to factor IX deficiency.


name: thrombophilia, X-linked, due to factor 9 defect

description: A hemostatic disorder characterized by a tendency to thrombosis that has X-linked recessive inheritance, and can be caused by a gain-of-function mutation in the gene encoding factor IX (F9).


karyomegalic interstitial nephritis

description: Any interstitial nephritis in which the cause of the disease is a mutation in the FAN1 gene.


prostate cancer, hereditary, 12

description: Any familial prostate cancer in which the cause of the disease is a mutation in the EHBP1 gene.


name: inflammatory skin and bowel disease, neonatal, 2

description: Any neonatal inflammatory skin and bowel disease in which the cause of the disease is a mutation in the EGFR gene.


Kleefstra syndrome 1

description: An autosomal dominant non-syndromic intellectual disability that has material basis in an autosomal dominant mutation of EHMT1 on chromosome 9q34.3.


name: primary intraosseous venous malformation

description: Primary intraosseous venous malformation is a rare, genetic vascular anomaly characterized by severe blood vessel expansion (most frequently within the craniofacial bones) with painless bone enlargement (usually of mandibule, maxilla and/or orbital, nasal, and frontal bones), typically resulting in facial asymmetry and contour deformation. Midline abnormalities, such as diastasis recti, supraumbilical raphe, and hiatus hernia, are commonly associated. Additional features reported include gingival bleeding, ectopic tooth eruption, exophthalmos, loss of vision, nausea, and vomiting.


name: autosomal recessive nonsyndromic hearing loss 36

description: Any autosomal recessive nonsyndromic deafness in which the cause of the disease is a mutation in the ESPN gene.


name: autosomal recessive nonsyndromic hearing loss 25

description: Any autosomal recessive nonsyndromic deafness in which the cause of the disease is a mutation in the GRXCR1 gene.


name: autosomal recessive nonsyndromic hearing loss 101

description: Any autosomal recessive nonsyndromic deafness in which the cause of the disease is a mutation in the GRXCR2 gene.


congenital factor XII deficiency

description: Congenital factor XII deficiency is an autosomal recessive systemic dysfunction of the hemostatic pathway, that is due to a defect in the coagulation factor XII (FXII or Hageman factor), and is either asymptomatic or characterized by a prolonged activated partial thromboplastin time and an increased risk for thromboembolism. FXII deficiency is strongly associated with primary recurrent abortions.


hereditary angioedema type 3

description: Hereditary angioedema type 3 (HAE 3) is a form of hereditary angioedema characterized by acute edema in subcutaneous tissues, viscera and/or the upper airway.


amelogenesis imperfecta type 1G

description: An extremely rare syndrome which is characterized by hypoplastic amelogenesis imperfecta (hypoplastic dental enamel) and nephrocalcinosis (precipitation of calcium salts in renal tissue). Oral manifestations include yellow and misshaped teeth, delayed tooth eruption, and intrapulpal calcifications. Nephrocalcinosis is often asymptomatic but can progress during late childhood or early adulthood to impaired renal function (e.g. recurrent urinary infections and renal tubular acidosis), and rarely to end-stage renal failure.


name: glutathione synthetase deficiency with 5-oxoprolinuria


name: glutathione synthetase deficiency without 5-oxoprolinuria


fructose-1,6-bisphosphatase deficiency

description: Fructose-1,6-biphosphatase (FBP) deficiency is a disorder of fructose metabolism characterized by recurrent episodes of fasting hypoglycemia with lactic acidosis, that may be life-threatening in neonates and infants.


lethal osteosclerotic bone dysplasia

description: Generalized osteosclerosis with periosteal bone formation, characteristic facial dysmorphism, brain abnormalities including intracerebral calcifications, and neonatal lethal course.


hereditary spastic paraplegia 35

description: Autosomal recessive spastic paraplegia type 35 is a rare form of hereditary spastic paraplegia characterized by childhood (exceptionally adolescent) onset of a complex phenotype presenting with lower limb (followed by upper limb) spasticity with hyperreflexia and extensor plantar responses, with additional manifestations including progressive dysarthria, dystonia, mild cognitive decline, extrapyramidal features, optic atrophy and seizures. White matter abnormalities and brain iron accumulation have also been observed on brain magnetic resonance imaging.


FADD-related immunodeficiency

description: A rare genetic immunological disease reported in a single consanguineous Pakistani family with several affected members presenting with severe bacterial and viral infections, recurrent hepatopathy (portal inflammation, fibrosis), and recurrent, stereotypical febrile episodes, sometimes lasting several days, with encephalopathy and difficult-to-control seizures. Variable cardiac malformations were also reported. Although there were autoimmune lymphoproliferative syndrome (ALPS)-like biological features, clinical ALPS was not present. A homozygous missense mutation in the FADD gene (11q13.3) was found in the family and the disease is thought to follow an autosomal recessive pattern of inheritance.


Fanconi anemia complementation group G

description: Fanconi anemia caused by mutations of the FANCG gene.


name: congenital diarrhea 5 with tufting enteropathy

description: Congenital Tufting Enteropathy is a rare congenital enteropathy presenting with early-onset severe and intractable diarrhea that leads to irreversible intestinal failure.


name: COLORECTAL CANCER, HEREDITARY NONPOLYPOSIS, TYPE 8


colorectal cancer

description: A primary or metastatic malignant neoplasm that affects the colon or rectum. Representative examples include carcinoma, lymphoma, and sarcoma.


pontocerebellar hypoplasia type 1B

description: Any non-syndromic pontocerebellar hypoplasia in which the cause of the disease is a mutation in the EXOSC3 gene.


name: neuronopathy, distal hereditary motor, type 2D

description: Any neuronopathy, distal hereditary motor in which the cause of the disease is a mutation in the FBXO38 gene.


Fanconi anemia complementation group D2

description: Fanconi anemia caused by mutations of the FANCD2 gene. This gene is involved in the repair of DNA double-strand breaks, both by homologous recombination and single-strand annealing.


name: mandibuloacral dysplasia with type B lipodystrophy


restrictive dermopathy 1

description: A restrictive dermopathy that has material basis in homozygous or compound heterozygous mutation in the ZMPSTE24 gene on chromosome 1p34.


name: cutis laxa, autosomal recessive, type 1B

description: An autosomal recessive cutis laxa type I characterized by disturbed elastic fiber formation resulting in severe systemic connective tissue abnormalities that has material basis in homozygous or compound heterozygous mutation in the EFEMP2 gene on chromosome 11q13.


tyrosinemia type I

description: Tyrosinemia type 1 (HTI) is an inborn error of tyrosine catabolism caused by defective activity of fumarylacetoacetate hydrolase (FAH) and is characterized by progressive liver disease, renal tubular dysfunction, porphyria-like crises and a dramatic improvement in prognosis following treatment with nitisinone.


van Maldergem syndrome 2

description: Any van Maldergem syndrome in which the cause of the disease is a mutation in the FAT4 gene.


name: Hennekam lymphangiectasia-lymphedema syndrome 2

description: Any Hennekam syndrome in which the cause of the disease is a mutation in the FAT4 gene.


Fanconi anemia complementation group C

description: Fanconi anemia caused by mutations of the FANCC gene. This gene provides instructions for making a protein that delays the onset of apoptosis and promotes homologous recombination repair of damaged DNA.


mitochondrial DNA depletion syndrome 13

description: Any mitochondrial DNA depletion syndrome in which the cause of the disease is a mutation in the FBXL4 gene.


Doyne honeycomb retinal dystrophy

description: Doyne honeycomb retinal dystrophy (DHRD) is a condition that affects the eyes and causes vision loss. It is characterized bysmall, round, white spots known as drusen that accumulate beneath the retinal pigment epithelium(the pigmented layer of the retina). Over time, drusen may grow and come together, creating a honeycomb pattern. It usually begins in early to mid adulthood, but the age of onset varies.The degree of vision loss also varies. DHRD is usually caused by mutations in the EFEMP1 gene and is inherited in an autosomal dominant manner.


congenital contractural arachnodactyly

description: Congenital contractural arachnodactyly (CCA, Beals syndrome) is a connective tissue disorder characterized by multiple flexion contractures, arachnodactyly, severe kyphoscoliosis, abnormal pinnae and muscular hypoplasia.


Unverricht-Lundborg syndrome

description: Unverricht-Lundborg disease (ULD) is a rare progressive myoclonic epilepsy disorder characterized by action- and stimulus-sensitive myoclonus, and tonic-clonic seizures with ataxia, but with only a mild cognitive decline over time.


hepatocellular carcinoma

description: A malignant tumor that arises from hepatocytes. Hepatocellular carcinoma is relatively rare in the United States but very common in all African countries south of the Sahara and in Southeast Asia. Most cases are seen in patients over the age of 50 years, but this tumor can also occur in younger individuals and even in children. Hepatocellular carcinoma is more common in males than females and is associated with hepatitis B, hepatitis C, chronic alcohol abuse and cirrhosis. Serum elevation of alpha-fetoprotein occurs in a large percentage of patients with hepatocellular carcinoma. Grossly, hepatocellular carcinoma may present as a single mass, as multiple nodules, or as diffuse liver involvement. Microscopically, there is a wide range of differentiation from tumor to tumor (well differentiated to poorly differentiated tumors). Hepatocellular carcinomas quickly metastasize to regional lymph nodes and lung. The overall median survival of untreated liver cell carcinoma is about 4 months. The most effective treatment of hepatocellular carcinoma is complete resection of the tumor. Lately, an increasing number of tumors have been treated with liver transplantation.


Joubert syndrome 25

description: Any Joubert syndrome in which the cause of the disease is a mutation in the CEP104 gene.


name: MELANOMA, CUTANEOUS MALIGNANT, SUSCEPTIBILITY TO, 2


MELANOMA-PANCREATIC CANCER SYNDROME

description: An inherited condition caused by autosomal dominant mutation(s) in the CDKN2A gene, encoding cyclin-dependent kinase inhibitor 2A. The condition is characterized by an increased risk of developing melanoma and/or pancreatic carcinoma.


name: melanoma and neural system tumor syndrome

description: An inherited condition caused by autosomal dominant mutation(s) in the CDKN2A gene, encoding cyclin-dependent kinase inhibitor 2A. The condition is characterized by an increased risk of developing melanoma and/or cerebral astrocytoma.


hereditary spastic paraplegia 13

description: Any hereditary spastic paraplegia in which the cause of the disease is a mutation in the HSPD1 gene.


hypomyelinating leukodystrophy 4

description: Any leukodystrophy in which the cause of the disease is a mutation in the HSPD1 gene.


name: developmental and epileptic encephalopathy 94

description: An idiopathic generalized epilepsy characterized by onset of multiple seizure types in the first few years of life and associated with poor prognosis. Affected individuals have cognitive regression and intellectual disability.


name: neuronopathy, distal hereditary motor, autosomal recessive 5

description: Young adult-onset distal hereditary motor neuropathy is a rare autosomal recessive distal hereditary motor neuropathy characterized by slowly progressive muscular weakness, hypotonia and atrophy of the lower limbs, more pronounced distally, leading to paralysis, and loss of tendon reflexes. Additional features may include pes cavus and mild dysphonia. The upper limbs are relatively spared.


name: autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6)

description: Autosomal dominant limb-girdle muscular dystrophy type 1D (LGMD1D) is a subtype of autosomal dominant limb-girdle muscular dystrophy characterized by an adult-onset of slowly progressive, proximal pelvic girdle weakness, with none, or only minimal, shoulder girdle involvement, and absence of cardiac and respiratory symptoms. Mild to moderate elevated creatine kinase serum levels and gait abnormalities are frequently observed. LGMD1D is caused by heterozygous missense mutations in the DNAJB6 gene at chr. 7q36.3.


name: juvenile-onset diabetes mellitus-central and peripheral neurodegeneration syndrome


name: ceroid lipofuscinosis, neuronal, 4 (Kufs type)

description: A condition associated with mutation(s) in the DNAJC5 gene, encoding dnaJ homolog subfamily C member 5. The condition is one of a group of genetically heterogeneous neurodegenerative disorders, characterized by accumulation of intracellular lipopigments.


Filippi syndrome

description: Filippi syndrome is characterized by microcephaly, cutaneous syndactyly of the fingers and toes, intellectual deficit, growth retardation and a characteristic facies (high and broad nasal bridge, thin alae nasi, micrognathia and a high frontal hairline). So far, less than 25 cases have been reported. Cryptorchidism, polydactyly, and teeth and hair anomalies may also be present. Transmission is autosomal recessive.


DNA ligase IV deficiency

description: LIG4 syndrome is a hereditary disorder associated with impaired DNA double-strand break repair mechanisms and characterized by microcephaly, unusual facial features, growth and developmental delay, skin anomalies, and pancytopenia, which is associated with combined immunodeficiency (CID).


name: severe combined immunodeficiency due to DCLRE1C deficiency

description: Severe combined immunodeficiency (SCID) due to DCLRE1C deficiency is a type of SCID characterized by severe and recurrent infections, diarrhea, failure to thrive, and cell sensitivity to ionizing radiation.


nephropathic cystinosis

description: An autosomal recessive condition caused by mutation(s) in the CTNS gene, encoding cystinosin. It is a sub-type of cystinosis, in which accumulation of cystine in the kidney results in renal dysfunction.


ocular cystinosis

description: Ocular cystinosis is the benign, adult form of cystinosis, a metabolic disease characterized by an accumulation of cystine crystals in the cornea and conjunctiva responsible for tearing and photophobia and associated with no other additional manifestations.


juvenile nephropathic cystinosis

description: Nephropathic juvenile cystinosis is the intermediate form, in regards to severity and age of onset, of cystinosis, a metabolic disease characterized by an accumulation of cystine inside the lysosomes that causes damage in different organs and tissues, particularly in the kidneys and eyes.


name: arrhythmogenic right ventricular dysplasia 13

description: Any arrhythmogenic right ventricular cardiomyopathy in which the cause of the disease is a mutation in the CTNNA3 gene.


name: microcephaly 17, primary, autosomal recessive

description: Any autosomal recessive primary microcephaly in which the cause of the disease is a mutation in the CIT gene.


name: autosomal recessive congenital ichthyosis 5

description: An autosomal recessive congenital ichthyosis characterized by fine white or greyish-white scales, hyperkeratosis, moderate acanthosis, and moderate parakeratosis that has material basis in homozygous mutation in the CYP4F22 gene on chromosome 19p13.


name: classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency

description: The most common form of congenital adrenal hyperplasia (CAH), characterized by simple virilizing or salt wasting forms that can manifest with genital ambiguity in females and with adrenal insufficiency (in both sexes), and that presents with dehydration, hypoglycemia in the neonatal period (that can be lethal if untreated), and hyperandrogenia.


cataract 22 multiple types

description: Any early-onset non-syndromic cataract in which the cause of the disease is a mutation in the CRYBB3 gene.


cataract 2, multiple types

description: Any cataract in which the cause of the disease is a mutation in the CRYGC gene.


cataract 4 multiple types

description: Any cataract (disease) in which the cause of the disease is a mutation in the CRYGD gene.


myofibrillar myopathy 2

description: Any autosomal dominant distal myopathy in which the cause of the disease is a mutation in the CRYAB gene.


cataract 16 multiple types

description: Any early-onset non-syndromic cataract in which the cause of the disease is a mutation in the CRYAB gene.


name: fatal infantile hypertonic myofibrillar myopathy


dilated cardiomyopathy 1II

description: Any familial isolated dilated cardiomyopathy in which the cause of the disease is a mutation in the CRYAB gene.


name: cerebellar atrophy, visual impairment, and psychomotor retardation;


name: leukoencephalopathy, diffuse hereditary, with spheroids 1

description: A rare autosomal dominant disease characterized by a complex phenotype including progressive dementia, apraxia, apathy, impaired balance, parkinsonism, spasticity and epilepsy.


nephrotic syndrome, type 10

description: Any nephrotic syndrome in which the cause of the disease is a mutation in the EMP2 gene.


protein-losing enteropathy

description: Pathological conditions in the intestines that are characterized by the gastrointestinal loss of serum proteins, including serum albumin; immunoglobulins; and at times lymphocytes. Severe condition can result in hypogammaglobulinemia or lymphopenia. Protein-losing enteropathies are associated with a number of diseases including intestinal lymphangiectasis; whipple'S disease; and neoplasms of the small intestine.


isolated congenital megalocornea

description: Isolated congenital megalocornea is a genetic, non-syndromic developmental defect of the anterior eye segment characterized by bilateral enlargement of the corneal diameter (>12.5 mm) and a deep anterior eye chamber, without an elevation in intraocular pressure. It can manifest with mild to moderate myopia as well as photophobia and iridodonesis (due to iris hypoplasia). Associated complications include lens dislocation, retinal detachment, presenile cataract development, and secondary glaucoma.


periventricular nodular heterotopia 6

description: Any periventricular nodular heterotopia in which the cause of the disease is a mutation in the ERMARD gene.


dilated cardiomyopathy 1M

description: Any familial isolated dilated cardiomyopathy in which the cause of the disease is a mutation in the CSRP3 gene.


hypertrophic cardiomyopathy 12

description: Any hypertrophic cardiomyopathy in which the cause of the disease is a mutation in the CSRP3 gene.


name: hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome

description: An autosomal dominant condition caused by mutations(s) in the CTBP1 gene, encoding C-terminal-binding protein 1. It is characterized by hypotonia, ataxia, developmental delay, and tooth enamel defects.


Joubert syndrome 21

description: Any Joubert syndrome in which the cause of the disease is a mutation in the CSPP1 gene.


name: cerebroretinal microangiopathy with calcifications and cysts 1

description: Any Coats plus syndrome in which the cause of the disease is a mutation in the CTC1 gene.


name: intellectual disability-feeding difficulties-developmental delay-microcephaly syndrome


name: congenital cataracts-facial dysmorphism-neuropathy syndrome

description: Congenital Cataracts Facial Dysmorphism Neuropathy (CCFDN) syndrome is a complex developmental disorder of autosomal recessive inheritance.


type 1 diabetes mellitus 12

description: An inherited susceptibility or predisposition to developing type 1 diabetes mellitus in which the cause of the disease is a mutation in the CTLA4 gene.


celiac disease, susceptibility to, 3

description: Any celiac disease in which the cause of the disease is a mutation in the CTLA4 gene.


name: autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency

description: A somatic mutation in the CTLA4 gene resulting in only a single functional gene. Haploinsufficiency for CTLA4 is associated with autoimmune lymphoproliferative syndrome, type V.


pilomatrixoma

description: Pilomatrixoma is a rare and benign hair cell-derived tumor occurring mostly in young adults (usually under the age of 20) and characterized as a 3-30 mm solitary, painless, firm, mobile, deep dermal or subcutaneous tumor, most commonly found in the head, neck or upper extremities. When superficial, the tumors tint the skin blue-red. Multiple pilomatrixomas are seen in myotonic dystrophy, Gardner syndrome, Rubinstein-Taybi syndrome, and Turner syndrome.


medulloblastoma

description: A malignant, invasive embryonal neoplasm arising from the cerebellum. It occurs predominantly in children and has the tendency to metastasize via the cerebrospinal fluid pathways. Signs and symptoms include truncal ataxia, disturbed gait, lethargy, headache, and vomiting. There are four histologic variants: classic medulloblastoma, large cell/anaplastic medulloblastoma, desmoplastic/nodular medulloblastoma, and medulloblastoma with extensive nodularity.


malignant mesothelioma

description: A malignant neoplasm of the pleura or peritoneum, arising from mesothelial cells. It is associated with exposure to asbestos.


name: severe intellectual disability-progressive spastic diplegia syndrome

description: Severe intellectual disability-progressive spastic diplegia syndrome is a rare condition that has been described in a few people with severe intellectual disability. Other signs and symptoms include progressive microcephaly (very small head); ataxia (lack of coordination); spasticity ; and/or skin, hair and mild facial anomalies. It is caused by changes (mutations) in the CTNNB1 gene and it is inherited in an autosomal dominant fashion. Treatment is based on the signs and symptoms present in each person.


3M syndrome 1

description: Any 3-M syndrome in which the cause of the disease is a mutation in the CUL7 gene.


name: Bietti crystalline corneoretinal dystrophy

description: Bietti's crystalline dystrophy (BCD) is a rare progressive autosomal recessive tapetoretinal degeneration disease, occurring in the third decade of life, characterized by small sparkling crystalline deposits in the posterior retina and corneal limbus in addition to sclerosis of the choroidal vessels and manifesting as nightblindness, decreased vision, paracentral scotoma, and, in the end stages of the disease, legal blindness.


D-2-hydroxyglutaric aciduria 1

description: Any D-2-hydroxyglutaric aciduria in which the cause of the disease is a mutation in the D2HGDH gene.


name: hydrocephalus, nonsyndromic, autosomal recessive 1

description: Any congenital hydrocephalus in which the cause of the disease is a mutation in the CCDC88C gene.


spinocerebellar ataxia type 40

description: Spinocerebellar ataxia type 40 (SCA40) is a very rare subtype of autosomal dominant cerebellar ataxia type 1, characterized by the adult-onset of unsteady gait and dysarthria, followed by wide-based gait, gait ataxia, ocular dysmetria, intention tremor, scanning speech, hyperreflexia and dysdiadochokinesis.


Omenn syndrome

description: An inflammatory condition characterized by erythroderma, desquamation, alopecia, chronic diarrhea, failure to thrive, lymphadenopathy, and hepatosplenomegaly, associated with severe combined immunodeficiency (SCID).


congenital factor VII deficiency

description: Factor VII (FVII) deficiency is a rare hereditary hemorrhagic disease caused by the diminution or absence of this coagulation factor.


amelogenesis imperfecta, type 3A

description: Any amelogenesis imperfecta in which the cause of the disease is a mutation in the FAM83H gene.


primary ciliary dyskinesia 13

description: Any primary ciliary dyskinesia in which the cause of the disease is a mutation in the DNAAF1 gene.


Woodhouse-Sakati syndrome

description: Woodhouse-Sakati syndrome is a multisystemic disorder characterized by hypogonadism, alopecia, diabetes mellitus, intellectual deficit and extrapyramidal signs with choreoathetoid movements and dystonia.


malonic aciduria

description: Malonic aciduria is a metabolic disorder caused by deficiency of malonyl-CoA decarboxylase (MCD).


name: lethal occipital encephalocele-skeletal dysplasia syndrome

description: Lethal occipital encephalocele-skeletal dysplasia syndrome is a rare, genetic, bone development disorder characterized by occipital and parietal bone hypoplasia leading to occipital encephalocele, calvarial mineralization defects, craniosynostosis, radiohumeral fusions, oligodactyly and other skeletal anomalies (arachnodactyly, terminal phalangeal aplasia of the thumbs, bilateral absence of the great toes, pronounced bilateral angulation of femora, shortened limbs, advanced osseous maturation). Fetal death in utero is associated.


hereditary spastic paraplegia 56

description: Any hereditary spastic paraplegia in which the cause of the disease is a mutation in the CYP2U1 gene.


peeling skin syndrome 4

description: Any peeling skin syndrome in which the cause of the disease is a mutation in the CSTA gene.


name: hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency


name: congenital generalized lipodystrophy type 4

description: Any congenital generalized lipodystrophy in which the cause of the disease is a mutation in the CAVIN1 gene.


carboxypeptidase N deficiency

description: An autosomal recessive condition caused by mutation(s) in the CPN1 gene, encoding carboxypeptidase N catalytic chain. It may be characterized by episodic angioedema, chronic urticaria, asthma and/or allergic hypersensitivity.


name: autosomal recessive nonsyndromic hearing loss 32

description: An autosomal recessive nonsyndromic deafness that is characterized by prelingual onset with severe to profound, stable hearing loss and has material basis in variation in the chromosome region 1p22.1-p13.3.


name: Rubinstein-Taybi syndrome due to CREBBP mutations

description: Any Rubinstein-Taybi syndrome in which the cause of the disease is a mutation in the CREBBP gene.


long QT syndrome 15

description: Any long QT syndrome in which the cause of the disease is a mutation in the CALM2 gene.


name: anemia, congenital dyserythropoietic, type 1a


Meier-Gorlin syndrome 4

description: Any Meier-Gorlin syndrome in which the cause of the disease is a mutation in the CDT1 gene.


name: cone-rod synaptic disorder, congenital nonprogressive


name: epilepsy, childhood absence, susceptibility to, 6

description: An inherited susceptibility or predisposition to developing child absence epilepsy or idiopathic generalized epilepsy, in which the cause of the disease is a mutation in the CACNA1H gene.


spinocerebellar ataxia type 6

description: Spinocerebellar ataxia type 6 (SCA6) is the most common subtype of autosomal dominant cerebellar ataxia type III (ADCA type III) characterized by late-onset and slowly progressive gait ataxia and other cerebellar signs such as impaired muscle coordination and nystagmus.


migraine, familial hemiplegic, 1

description: An autosomal dominant subtype of familial hemiplegic migraine caused by mutation(s) in the CACNA1A gene, encoding voltage-dependent P/Q-type calcium channel subunit alpha-1A.


episodic ataxia type 2

description: Episodic ataxia type 2 (EA2) is the most frequent form of Hereditary episodic ataxia (EA) characterized by paroxysmal episodes of ataxia lasting hours, with interictal nystagmus and mildly progressive ataxia.


name: developmental and epileptic encephalopathy, 42

description: Any early infantile epileptic encephalopathy in which the cause of the disease is a mutation in the CACNA1A gene.


name: multiple mitochondrial dysfunctions syndrome 3

description: Any fatal multiple mitochondrial dysfunctions syndrome in which the cause of the disease is a mutation in the IBA57 gene.


hereditary spastic paraplegia 74

description: Autosomal recessive spastic paraplegia type 74 is a rare, genetic, spastic paraplegia-optic atrophy-neuropathy-related (SPOAN-like) disorder characterized by childhood onset of mild to moderate spastic paraparesis which manifests with gait impairment that very slowly progresses into late adulthood, hyperactive patellar reflex and bilateral extensor plantar response, in association with optic atrophy and typical symptoms of peripheral neuropathy, including reduced or absent ankle reflexes, lower limb atrophy and distal sensory impairment. Reduced visual acuity and pes cavus are frequently reported.


name: autoimmune lymphoproliferative syndrome type 2A

description: A rare, primary immunodeficiency with an autosomal dominant pattern of inheritance but incomplete penetrance. It is caused by a mutation in the CASP10 (caspase-10) gene that leads to defective Fas-induced apoptosis. Disruption of Fas-induced apoptosis impairs lymphocyte homeostasis and immune tolerance. Characteristic laboratory findings include an increase in circulating, double-negative (CD4-/CD8-) T cells in the setting of immune-mediated anemia, thrombocytopenia and neutropenia. Clinical signs present in childhood include fatigue, pallor, bruising, hepatosplenomegaly and chronic, non-malignant, non-infectious lymphadenopathy. The clinical course is influenced by a strong association with other autoimmune disorders and an increased risk for developing Hodgkin and non-Hodgkin lymphoma.


CBL-related disorder

description: CBL-related disorder is a genetic condition caused by pathogenic variants in the Cbl ubiquitin ligase gene, (CBL; HGNC:1541). Due to the proposed mechanism indicating the CBL gene's relationship to the RAS-MAPK pathway and the phenotypic presentation similar to that of the RASopathies, CBL-related disorder should be considered a RASopathy disorder. Though there is a wide spectrum of phenotypic variability, broadly, patients with CBL-related disorder have presented with developmental delay, intellectual disability, neurodevelopmental alterations, prenatal lymphatic anomalies, cardiac malformations as well as vascular anomalies particularly affecting the brain (e.g. Moya-moya arteriopathies), craniofacial features indicative of a RASopathy, hypotonia, feeding difficulties, edema of the legs, musculoskeletal and respiratory thorax abnormalities, ectodermal features including cafe-au-lait spots, immunological and hematological disorders and susceptibility to tumors diagnosed as juvenile myelomonocytic leukemia (JMML) that is usually self-remitting. Note tumor risk beyond JMML has not yet been thoroughly assessed. Due to the clinical presentation of a broad spectrum of these and other phenotypes in patients with variants in CBL, these conditions are currently defined by experts in reference to the causal gene, CBL.


name: intellectual disability, autosomal dominant 10

description: Any autosomal dominant non-syndromic intellectual disability in which the cause of the disease is a mutation in the CACNG2 gene.


name: developmental and epileptic encephalopathy, 2

description: Any early infantile epileptic encephalopathy in which the cause of the disease is a mutation in the CDKL5 gene.


acatalasia

description: A congenital disorder resulting from a deficiency in erythrocyte catalase, an enzyme responsible for the breakdown of hydrogen peroxide.


name: ichthyosis, congenital, autosomal recessive 12

description: Any autosomal recessive congenital ichthyosis in which the cause of the disease is a mutation in the CASP14 gene.


name: autosomal dominant nonsyndromic hearing loss 44

description: Any autosomal dominant nonsyndromic deafness in which the cause of the disease is a mutation in the CCDC50 gene.


hyper-IgM syndrome type 1

description: The X-linked variant of the Hyper-IgM syndrome. The affected individuals are virtually always male, because males only have one X chromosome, received from their mothers. Their mothers are not symptomatic, even though they are carriers of the allele, because the trait is recessive. Male offspring of these women have a 50% chance of inheriting their mother's mutant allele.


name: susceptibility to respiratory infections associated with CD8alpha chain mutation

description: Susceptibility to respiratory infections associated with CD8 alpha chain mutation is a rare primary immunodeficiency due to a defect in adaptive immunity characterized by the absence of CD8+ T cells with normal immunoglobulin and specific antibody titres in blood and susceptibility to recurrent respiratory bacterial and viral infections. Symptom severity range from fatal respiratory insufficiency to mild or asymptomatic phenotypes.


name: congenital generalized lipodystrophy type 3

description: Any congenital generalized lipodystrophy in which the cause of the disease is a mutation in the CAV1 gene.


pulmonary hypertension, primary, 3

description: Any primary pulmonary hypertension in which the cause of the disease is a mutation in the CAV1 gene.


name: partial lipodystrophy, congenital cataracts, and neurodegeneration syndrome


name: myopathy due to calsequestrin and SERCA1 protein overload

description: Myopathy due to calsequestrin and SERCA1 protein overload is characterized by mild myopathy or elevated levels of creatine kinase in the blood without associated symptoms.


myopathy, tubular aggregate, 1

description: Any tubular aggregate myopathy in which the cause of the disease is a mutation in the STIM1 gene.


pycnodysostosis

description: Pycnodysostosis is a genetic lysosomal disease characterized by short stature, increased density of the bones (osteosclerosis/osteopetrosis), and brittle bones. Other features may include underdevelopment of the tips of the fingers with absent or small nails, an abnormal collarbone (clavicle), distinctive facial features including a large head with a small face and chin, underdeveloped facial bones, a high forehead, and dental abnormalities.Pycnodysostosis is an autosomal recessive condition caused by mutations in the gene that codes the enzyme cathepsin K (CTSK) on chromosome 1q21. The diagnosis of pycnodysostosis is based on physical features and X-ray findings. Molecular genetic testing is available. Treatment should address the symptoms found in each patient and may include orthopedic monitoring, treatment of fractures, appropriate dental care, and craniofacial surgery.


corneal dystrophy, Fuchs endothelial, 8

description: Any Fuchs' endothelial dystrophy in which the cause of the disease is a mutation in the AGBL1 gene.


primary ciliary dyskinesia 30

description: Any primary ciliary dyskinesia in which the cause of the disease is a mutation in the CCDC151 gene.


Bardet-Biedl syndrome 1

description: A Bardet-Biedl syndrome that has material basis in homozygous mutation in the BBS1 gene on chromosome 11q13.


description: Any megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome in which the cause of the disease is a mutation in the CCND2 gene.


name: macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome


name: MELANOMA, CUTANEOUS MALIGNANT, SUSCEPTIBILITY TO, 3


name: autoimmune lymphoproliferative syndrome type 2B

description: Autoimmune lymphoproliferative syndrome (ALPS) with recurrent viral infections is a rare genetic disorder characterized by lymphadenopathy and/or splenomegaly and recurrent infections due to herpes viruses.


name: catecholaminergic polymorphic ventricular tachycardia 2

description: Any catecholaminergic polymorphic ventricular tachycardia in which the cause of the disease is a mutation in the CASQ2 gene.


familial temporal lobe epilepsy 5

description: A temporal lobe epilepsy that has material basis in heterozygous mutation in the CPA6 gene on chromosome 8q13.


retinitis pigmentosa 75

description: Any retinitis pigmentosa in which the cause of the disease is a mutation in the AGBL5 gene.


type 1 diabetes mellitus 22

description: An inherited susceptibility or predisposition to developing type 1 diabetes mellitus in which the cause of the disease is a mutation in the CCR5 gene.


name: combined immunodeficiency due to CD3gamma deficiency

description: Combined immunodeficiency due to CD3gamma deficiency is an extremely rare genetic combined primary immunodeficiency characterized by a selective partial lymphopenia (T+/-B+NK+) phenotype and decreased CD3 complex resulting in a variable but usually mild clinical presentation ranging from asymptomatic until adulthood to high susceptibility to infections from early infancy with predominant automimmune manifestations.


name: methylmalonic acidemia due to transcobalamin receptor defect

description: Methylmalonic aciduria due to transcobalamin receptor defect is a rare metabolite absorption and transport disorder characterized by a moderate increase of methylmalonic acid (MMA) in the blood and urine due to decreased cellular uptake of cobalamin resulting from decreased transcobalamin receptor function. Patients are usually asymptomatic however, screening reveals increased C3-acylcarnitine and MMA in plasma. Serum homocysteine levels may vary from normal to moderately elevated and retinal vascular occlusive disease, resulting in severe visual loss, has been reported.


Meier-Gorlin syndrome 7

description: Any Meier-Gorlin syndrome in which the cause of the disease is a mutation in the CDC45 gene.


Papillon-Lefevre disease

description: Papillon-Lefevre syndrome (PLS) is a rare ectodermal dysplasia characterized by palmoplantar keratoderma associated with early-onset periodontitis.


Haim-Munk syndrome

description: Haim-Munk syndrome (HMS) is characterized by palmoplantar hyperkeratosis, severe early-onset periodontitis, onychogryposis, pes planus, arachnodactyly and acroosteolysis.


periodontitis, aggressive 1

description: A localized aggressive periodontitis, formerly called localized juvenile periodontitis. It is a destructive form of periodontitis characterized by ALVEOLAR BONE LOSS of the MOLARS and INCISORS. Inflammation and loss of PERIODONTIUM that is characterized by rapid attachment loss and bone destruction in the presence of little local factors such as DENTAL PLAQUE and DENTAL CALCULUS. This highly destructive form of periodontitis often occurs in young people and was called early-onset periodontitis, but this disease also appears in old people.


primary ciliary dyskinesia 15

description: Any primary ciliary dyskinesia in which the cause of the disease is a mutation in the CCDC40 gene.


name: epidermolysis bullosa simplex 7, with nephropathy and deafness


immunodeficiency 25

description: Any severe combined immunodeficiency in which the cause of the disease is a mutation in the CD247 gene.


name: congenital myopathy with internal nuclei and atypical cores

description: Congenital myopathy with internal nuclei and atypical cores is a rare genetic skeletal muscle disease characterized by neonatal hypotonia, distal more than proximal muscle weakness, progressive exercise intolerance with prominent myalgias, and mild-to-moderate overall motor impairment with preserved ambulation. Face, extraocular, cardiac, and respiratory muscles are unaffected. Mild cognitive impairment is also noted in most patients.


cerebral cavernous malformation 2

description: Any familial cerebral cavernous malformation in which the cause of the disease is a mutation in the CCM2 gene.


primary ciliary dyskinesia 29

description: Any primary ciliary dyskinesia in which the cause of the disease is a mutation in the CCNO gene.


Al Kaissi syndrome

description: Al Kaissi syndrome is an autosomal recessive developmental disorder characterized by growth retardation, spine malformation, particularly of the cervical spine, dysmorphic facial features, and delayed psychomotor development with moderate to severe intellectual disability (summary by {1:Windpassinger et al., 2017}).


holoprosencephaly 11

description: Any holoprosencephaly in which the cause of the disease is a mutation in the CDON gene.


name: microcephaly 13, primary, autosomal recessive

description: Any autosomal recessive primary microcephaly in which the cause of the disease is a mutation in the CENPE gene.


progressive myoclonic epilepsy type 8

description: Any progressive myoclonic epilepsy in which the cause of the disease is a mutation in the CERS1 gene.


name: severe hypotonia-psychomotor developmental delay-strabismus-cardiac septal defect syndrome

description: Severe hypotonia-psychomotor developmental delay-strabismus-cardiac septal defect syndrome is a rare, genetic, non-dystrophic congenital myopathy disorder characterized by a neonatal-onset of severe generalized hypotonia associated with mild psychomotor delay, congenital strabismus with abducens nerve palsy, and atrial and/or ventricular septal defects. Cryptorchidism is commonly reported in male patients and muscle biopsy typically reveals increased variability in muscle fiber size.


plasma cell myeloma

description: A bone marrow-based plasma cell neoplasm characterized by a serum monoclonal protein and skeletal destruction with osteolytic lesions, pathological fractures, bone pain, hypercalcemia, and anemia. Clinical variants include non-secretory myeloma, smoldering myeloma, indolent myeloma, and plasma cell leukemia. (WHO, 2001)


aceruloplasminemia

description: An adult-onset disorder of neurodegeneration with brain iron accumulation (NBIA) characterized by anemia, retinal degeneration, diabetes and various neurological symptoms.


name: autosomal dominant nonsyndromic hearing loss 64

description: Any autosomal dominant nonsyndromic deafness in which the cause of the disease is a mutation in the DIABLO gene.


name: intellectual disability, autosomal dominant 24

description: Any autosomal dominant non-syndromic intellectual disability in which the cause of the disease is a mutation in the DEAF1 gene.


hyperinsulinism-hyperammonemia syndrome

description: Hyperinsulinism-hyperammonemia syndrome (HIHA) is a frequent form of diazoxide-sensitive diffuse hyperinsulinism, characterized by an excessive/ uncontrolled insulin secretion (inappropriate for the level of glycemia), asymptomatic hyperammonemia and recurrent episodes of profound hypoglycemia induced by fasting and protein rich meals, requiring rapid and intensive treatment to prevent neurological sequelae. Epilepsy and cognitive deficit that are unrelated to hypoglycemia may also occur.


name: spondyloepimetaphyseal dysplasia, Shohat type

description: A spondyloepimetaphyseal dysplasia characterized by severely disproportionate short stature, short limbs, small chest, short neck, thin lips, severe lumbar lordosis, marked genu varum, joint laxity, distended abdomen, mild hepatomegaly and splenomegaly.


keratosis palmoplantaris striata 2

description: Any striate palmoplantar keratoderma in which the cause of the disease is a mutation in the DSP gene.


name: arrhythmogenic cardiomyopathy with wooly hair and keratoderma

description: A cardioectodermal syndrome that is often associated with the gene DSP, encoding desmoplakin. Desmoplakin is a member of the plakin family of cell adhesion molecules that are responsible for the formation and maintenance of desmosomes. Variation in DSP is associated with cardiomyopathic manifestations that include: (1) seemingly isolated arrhythmogenic right ventricle cardiomyopathy (ARVC) that is atypical and can show left ventricle dominance, or be present in the left and right ventricle simultaneously; and (2) dilated cardiomyopathy. Cutaneous phenotypes including wooly hair and/or keratoderma can present along with the cardiomyopathy, but are noted as less penetrant features.


name: arrhythmogenic right ventricular dysplasia 8

description: Any arrhythmogenic right ventricular cardiomyopathy in which the cause of the disease is a mutation in the DSP gene.


name: lethal acantholytic epidermolysis bullosa

description: Lethal acantholytic epidermolysis bullosa is a suprabasal subtype of epidermolysis bullosa simplex (EBS) characterized by generalized oozing erosions, usually in the absence of blisters.


name: cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis


paragangliomas 1

description: Any paraganglioma in which the cause of the disease is a mutation in the SDHD gene.


pheochromocytoma

description: Pheochromocytomas (also known as chromaffin tumors) produce, store, and secrete catecholamines. Pheochromocytomas usually originate from the adrenal medulla but may also develop from chromaffin cells in or about sympathetic ganglia. A common symptom of pheochromocytoma is hypertension owing to release of catecholamines.


Carney-Stratakis syndrome

description: A rare, autosomal dominant inherited neoplastic syndrome caused by mutations in the genes that code the succinate dehydrogenase protein complex. It is charcaterized by the presence of gastrointestinal stromal tumors and paragangliomas.


name: mitochondrial complex II deficiency, nuclear type 1

description: Complex II deficiency is a mitochondrial disease. Mitochondria are specialized compartments in cells that create more than 90% of the energy needed by the body. In mitochondrial diseases, the mitochondria don't work correctly resulting in less energy in the cell, cell injury and cell death. The signs and symptoms of mitochondrial complex II deficiency can vary greatly from severe life-threatening symptoms in infancy to muscle disease beginning in adulthood. Complex II deficiency can be caused by mutations in the SDHA, SDHB, SDHD, or SDHAF1 genes. In many cases the underlying gene mutations cannot be identified. Complex II deficiency is inherited in an autosomal recessive fashion. Complex II deficiency gene mutation carriers may be at an increased risk for certain cancers.


X-Linked Dyskeratosis Congenita

description: Dyskeratosis congenita inherited in an X-linked recessive pattern. It is caused by mutations in the DKC1 gene.


hereditary spastic paraplegia 28

description: Autosomal recessive spastic paraplegia type 28 is a pure form of hereditary spastic paraplegia characterized by a childhood or adolescent onset of slowly progressive, pure crural muscle spastic paraparesis which manifests with mild lower limb weakness, gait difficulties, extensor plantar responses, and hyperreflexia of lower extremities. Less common manifestations reported include cerebellar oculomotor disturbance with saccadic eye pursuit, pes cavus and scoliosis. Some patients also present pin and vibration sensory loss in distal legs.


name: progressive encephalopathy with leukodystrophy due to DECR deficiency

description: Progressive encephalopathy with leukodystrophy due to DECR deficiency is a rare mitochondrial disease, which presents with neonatal hypotonia, central nervous system abnormalities (ventriculomegaly, corpus callosum hypoplasia, cerebellar atrophy), acquired microcephaly, failure to thrive, developmental delay and intermittent lactic acidosis provoked by catabolic stress (e.g. infection). Hyperlysinemia and elevated C10:2 carnitine can be detected in plasma. Later on, epilepsy, cerebellar ataxia, renal tubular acidosis, severe encephalopathy, dystonia, spastic quadriplegia and other complications may develop.


intellectual disability, X-linked 102

description: An inherited condition caused by mutation(s) in the DDX3X gene, encoding ATP-dependent RNA helicase DDX3X. It is characterized by severe intellectual disability and variable neurologic features.


orofaciodigital syndrome V

description: Oral-facial-digital syndrome, type 5 is characterized by median cleft of the upper lip, postaxial polydactyly of hands and feet, and oral manifestations (duplicated frenulum).


Smith-Lemli-Opitz syndrome

description: Smith-Lemli-Opitz syndrome (SLOS) is characterized by multiple congenital anomalies, intellectual deficit, and behavioral problems.


name: neurodevelopmental disorder with severe motor impairment and absent language


pleuropulmonary blastoma

description: A malignant neoplasm affecting the lungs and/or the pleura. Pleuropulmonary blastoma is seen in children. Microscopically, the tumor may show features of chondrosarcoma, leiomyosarcoma, rhabdomyosarcoma, liposarcoma, or undifferentiated sarcoma. In approximately 25% of patients with pleuropulmonary blastoma, there are other lesions or neoplasms that may affect patients or their families, including lung or kidney cysts, and ovarian or testicular neoplasms. Heterozygous germline mutations in DICER1 gene have been identified in families harboring pleuropulmonary blastomas.


name: polycystic kidney disease 6 with or without polycystic liver disease

description: Any polycystic kidney disease in which the cause of the disease is a mutation in the DNAJB11 gene.


Duchenne muscular dystrophy

description: Duchenne muscular dystrophy (DMD) is a neuromuscular disease characterized by rapidly progressive muscle weakness and wasting due to degeneration of skeletal, smooth and cardiac muscle.


Becker muscular dystrophy

description: Becker muscular dystrophy (BMD) is a neuromuscular disease characterized by progressive muscle wasting and weakness due to degeneration of skeletal, smooth and cardiac muscle.


dilated cardiomyopathy 3B

description: Any dilated cardiomyopathy in which the cause of the disease is a mutation in the DMD gene.


name: developmental and epileptic encephalopathy, 49

description: Any early infantile epileptic encephalopathy in which the cause of the disease is a mutation in the DENND5A gene.


apparent mineralocorticoid excess

description: Apparent mineralocorticoid excess (AME) is a rare form of pseudohyperaldosteronism characterized by very early-onset and severe hypertension, associated with low renin levels and hypoaldosteronism.


dihydropteridine reductase deficiency

description: Dihydropteridine reductase (DHPR) deficiency is a severe form of hyperphenylalaninemia (HPA) due to impaired regeneration of tetrahydrobiopterin (BH4), leading to decreased levels of neurotransmitters (dopamine, serotonin) and folate in cerebrospinal fluid, and causing neurological symptoms such as psychomotor delay, hypotonia, seizures, abnormal movements, hypersalivation, and swallowing difficulties.


name: autosomal dominant nonsyndromic hearing loss 1

description: Any autosomal dominant nonsyndromic deafness in which the cause of the disease is a mutation in the DIAPH1 gene.


name: progressive microcephaly-seizures-cortical blindness-developmental delay syndrome

description: Progressive microcephaly-seizures-cortical blindness-developmental delay syndrome is a rare, genetic, neuro-ophthalmological syndrome characterized by post-natal, progressive microcephaly and early-onset seizures, associated with delayed global development, bilateral cortical visual impairment and moderate to severe intellectual disability. Additional manifestations include short stature, generalized hypotonia and pulmonary complications, such as recurrent respiratory infections and bronchiectasis. Auditory and metabolic screenings are normal.


name: autosomal dominant auditory neuropathy 1

description: Any auditory neuropathy in which the cause of the disease is a mutation in the DIAPH3 gene.


late-onset Parkinson disease

description: A Parkinson disease that begins after around the age of 50.


schizophrenia 9

description: A schizophrenia that has material basis in a mutation of DISC1 on chromosome 1q42.2.


name: hypophosphatemic rickets, autosomal recessive, 1

description: Any autosomal recessive hypophosphatemic rickets in which the cause of the disease is a mutation in the DMP1 gene.


nephronophthisis 19

description: Any nephronophthisis in which the cause of the disease is a mutation in the DCDC2 gene.


name: autosomal recessive nonsyndromic hearing loss 66

description: Any autosomal recessive nonsyndromic deafness in which the cause of the disease is a mutation in the DCDC2 gene.


name: isolated neonatal sclerosing cholangitis

description: Isolated neonatal sclerosing cholangitis is a rare, genetic, biliary tract disease characterized by severe neonatal-onset cholangiopathy with patent bile ducts and absence of ichthyosiform skin lesions. Patients present with jaundice, acholic stools, hepatosplenomegaly and high serum gamma-glutamyltransferase activity. Liver histology shows portal fibrosis, ductular proliferation, hepatocellular metallothionein deposits, and intralobular bile-pigment accumulations. Some patients may also have renal disease.


Warsaw breakage syndrome

description: A syndrome mainly characterized by severe growth retardation and microcephaly. It is a new form of cohesinopathy showing defects in sister chromatid cohesion and hypersensitivity to chemicals that induce replication stress, thus combining distinct cytogenetic features seen in Roberts syndrome and Fanconi anemia, respectively. It has material basis in homozygous or compound heterozygous mutation in the DDX11 gene on chromosome 12p11.


name: congenital diarrhea 7 with exudative enteropathy

description: Congenital chronic diarrhea with protein-losing enteropathy is a rare, genetic, intestinal disease characterized by early-onset, chronic, non-infectious, non-bloody, watery diarrhea associated with protein-losing enteropathy which results in hypoalbuminemia, hypogammaglobulinemia and elevated stool alpha-1-antitrypsin. Patients typically present severe, intractable diarrhea, failure to thrive, recurrent infections and edema.


spinocerebellar ataxia type 20

description: Spinocerebellar ataxia type 20 (SCA20) is a very rare subtype of type I autosomal dominant cerebellar ataxia (ADCA type I). It is characterized by cerebellar dysarthria as the initial typical manifestation.


d-bifunctional protein deficiency

description: A genetic disorder that affects the ability of the body to effectively break down fat from our diet. It is typically characterized by hypotonia (low muscle tone) and seizures in the newborn period. Other symptoms include unusual facial features and an enlarged liver (hepatomegaly). Most babies with this condition nevergain anydevelopmental skills and do not survive past the age of 2. DBP deficiency is caused by mutations in the HSD17B4 gene and is inherited in an autosomal recessive manner. Some researchers have suggested classifying DBP deficiency into three subtypes, depending on how severely the mutation in the HSD17B4 gene affects the function of the gene and the protein that it codes for. Almost all individuals with types I, II, and III have similar signs and symptoms. A fourth subtype has additionally been proposed for individuals that have less severe symptoms. While there is no cure for DBP deficiency, treatment is focused on improving nutrition and growth, controlling symptoms, and limiting the progression of liver disease.


Perrault syndrome 1

description: Any Perrault syndrome in which the cause of the disease is a mutation in the HSD17B4 gene.


name: 46,XY gonadal dysgenesis-motor and sensory neuropathy syndrome


retinitis pigmentosa 59

description: Any retinitis pigmentosa in which the cause of the disease is a mutation in the DHDDS gene.


name: developmental delay and seizures with or without movement abnormalities

description: DEDSM is a neurodevelopmental disorder characterized by global developmental delay, variable intellectual disability, and early-onset seizures with a myoclonic component. Most patients have delayed motor development and show abnormal movements, including ataxia, dystonia, and tremor (summary by {1:Hamdan et al., 2017}).


esophageal cancer

description: A primary or metastatic malignant neoplasm involving the esophagus.


myofibrillar myopathy 1

description: A rare genetic skeletal muscle disease characterized by abnormal chimeric aggregates of desmin and other cytoskeletal proteins and granulofilamentous material at the ultrastructural level in muscle biopsies and variable clinical/ myopathological features, age of disease onset and rate of disease progression. Patients present with bilateral skeletal muscle weakness that starts in distal leg muscles and spreads proximally, sometimes involving trunk, neck flexors and facial muscles and often cardiomyopathy manifested by conduction blocks, arrhythmias, chronic heart failure, and sometimes tachyarrhythmia. Weakness eventually leads to wheelchair dependence. Respiratory insufficiency can be a major cause of disability and death, beginning with nocturnal hyperventilation with oxygen desaturation and progressing to daytime respiratory failure.


dilated cardiomyopathy 1I

description: Any familial isolated dilated cardiomyopathy in which the cause of the disease is a mutation in the DES gene.


name: neurogenic scapuloperoneal syndrome, Kaeser type


description: Glomerulonephritis characterized by mesangial proliferation, endocapillary proliferation, and glomerular capillary wall remodeling with immune complex deposits from classical complement pathway activation.


desmosterolosis

description: Desmosterolosis is a very rare sterol biosynthesis disorder characterized by multiple congenital anomalies, failure to thrive, and intellectual disability, with elevated levels of desmosterol.


name: spondylocostal dysostosis 1, autosomal recessive


cortisone reductase deficiency 2

description: Decreased activity of the enzyme 11-beta-hydroxysteroid dehydrogenase type 1 due to inactivating mutation(s) in the HSD11B1 gene. The condition is characterized by hyperandrogenism as a result of increased adrenocorticotropic hormone stimulation of the adrenal gland due to failure of cortisol-mediated down-regulation, and is clinically indistinguishable from H6PD deficiency.


name: Charcot-Marie-Tooth disease axonal type 2Q

description: Autosomal dominant Charcot-Marie-Tooth disease type 2Q is a rare subtype of autosomal dominant Charcot-Marie-Tooth disease type 2 characterized by adolescent to adulthood-onset of symmetrical, slowly progressive distal muscle weakness and atrophy (with a predominant weakness of the distal lower limbs) associated with reduced or absent deep tendon reflexes, pes cavus and mild to moderated deep sensory impairment.


bone marrow failure syndrome 3

description: Any bone marrow failure syndrome in which the cause of the disease is a mutation in the DNAJC21 gene.


hypotrichosis 6

description: Any hypotrichosis in which the cause of the disease is a mutation in the DSG4 gene.


name: hereditary hypotrichosis with recurrent skin vesicles

description: Hereditary hypotrichosis with recurrent skin vesicles is a very rare inherited hair loss disorder described in a family and characterized by sparse, fragile or absent hair on the scalp, eyebrows, eyelashes, axillae and rest of the body, associated with vesicle formation on various parts of the scalp and body which regularly burst and release watery fluid.


name: Ehlers-Danlos syndrome, musculocontractural type 2

description: Any Ehlers-Danlos syndrome, musculocontractural type in which the cause of the disease is a mutation in the DSE gene.


name: palmoplantar keratoderma i, striate, focal, or diffuse


name: severe dermatitis-multiple allergies-metabolic wasting syndrome


name: deafness, autosomal dominant 39, with dentinogenesis imperfecta 1


dentinogenesis imperfecta type 2

description: Dentinogenesis imperfecta type 2 (DGI-2) is a rare, severe form of dentinogenesis imperfecta (DGI) and is characterized by weakness and discoloration of all teeth.


dentinogenesis imperfecta type 3

description: Dentinogenesis imperfecta type 3 (DGI-3) is a rare, severe form of dentinogenesis imperfecta (DGI) characterized by opalescent primary and permanent teeth, marked attrition, large pulp chambers, multiple pulp exposure and shell teeth radiographically (i.e. teeth which appear hollow due to dentin hypotrophy).


dentin dysplasia type II

description: Dentin dysplasia type II (DD-II) is a rare mild form of dentin dysplasia (DD) characterized by normal tooth roots but abnormal primary dentition.


thyroid dyshormonogenesis 6

description: Any familial thyroid dyshormonogenesis in which the cause of the disease is a mutation in the DUOX2 gene.


tricho-dento-osseous syndrome

description: Tricho-dento-osseous dysplasia (TDO) belongs to the ectodermal dysplasias and is characterized by curly/kinky hair at birth, enamel hypoplasia with discolouration and molar taurodontism, increased overall bone mineral density (BMD) and increased thickness of the cortical bones of the skull.


name: hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism

description: Any amelogenesis imperfecta in which the cause of the disease is a mutation in the DLX3 gene.


intellectual disability, X-linked 90

description: Any non-syndromic X-linked intellectual disability in which the cause of the disease is a mutation in the DLG3 gene.


hereditary spastic paraplegia 46

description: A rare, complex type of hereditary spastic paraplegia characterized by an onset, in infancy or childhood, of the typical signs of spastic paraplegia (i.e. spastic gait and weakness of the lower limbs) associated with a variety of additional manifestations including upper limb spasticity and weakness, pseudobulbar dysarthria, bladder dysfunction, cerebellar ataxia, cataracts, and cognitive impairment that can progress to dementia. Brain imaging may show thinning of the corpus callosum and mild atrophy of the cerebrum and cerebellum. SPG46 is due to mutations in the GBA2 gene (9p13.2) encoding non-lysosomal glucosylceramidase.


name: intellectual disability, autosomal dominant 42

description: Any autosomal dominant intellectual disability in which the cause of the disease is a heterozygous mutation in the GNB1 gene. It is characterized by global developmental delay, intellectual disability, hypotonia, structural brain abnormalities, and seizures. Other less common findings include dystonia, visual impairment, behavior problems, growth delay, craniofacial defects, and genitourinary abnormalities in males.


name: arrhythmogenic right ventricular dysplasia 10

description: Any arrhythmogenic right ventricular cardiomyopathy in which the cause of the disease is a mutation in the DSG2 gene.


dilated cardiomyopathy 1BB

description: Any familial isolated dilated cardiomyopathy in which the cause of the disease is a mutation in the DSG2 gene.


dyschromatosis symmetrica hereditaria

description: Acropigmentation of Dohi is a genodermatosis characterized by the presence of hyperpigmented and hypopigmented macules, principally located on the extremities and limbs.


Aicardi-Goutieres syndrome 6

description: Any Aicardi-Goutieres syndrome in which the cause of the disease is a mutation in the ADAR gene.


name: epileptic encephalopathy, infantile or early childhood, 2


left ventricular noncompaction 1

description: Any left ventricular noncompaction in which the cause of the disease is a mutation in the DTNA gene.


name: recurrent Neisseria infections due to factor D deficiency


name: linear skin defects with multiple congenital anomalies 2

description: Any microphthalmia with linear skin defects syndrome in which the cause of the disease is a mutation in the COX7B gene.


name: Antibody Deficiency due to Defect in CD19


name: agammaglobulinemia 3, autosomal recessive

description: Any autosomal agammaglobulinemia in which the cause of the disease is a mutation in the CD79A gene.


Meier-Gorlin syndrome 5

description: Any Meier-Gorlin syndrome in which the cause of the disease is a mutation in the CDC6 gene.


name: immunodeficiency-centromeric instability-facial anomalies syndrome 3

description: Any immunodeficiency-centromeric instability-facial anomalies syndrome in which the cause of the disease is a mutation in the CDCA7 gene.


Perlman syndrome

description: Perlman syndrome is characterized principally by polyhydramnios, neonatal macrosomia, bilateral renal tumors (hamartomas with or without nephroblastomatosis), hypertrophy of the islets of Langerhans and facial dysmorphism.


IMAGe syndrome

description: IMAGe syndrome is characterized by the association of intrauterine growth retardation, metaphyseal dysplasia (and short limbs), adrenal hypoplasia congenita, and genital anomalies. It has been described in less than 20 cases. The patients also present with dysmorphic features (frontal bossing, broad nasal bridge, low-set ears). In boys, genital anomalies include bilateral cryptorchidism, hypospadias, micropenis, and hypogonadotropic hypogonadism. This syndrome is likely to be transmitted as an autosomal recessive trait.


Stromme syndrome

description: An autosomal recessive congenital disorder affecting multiple systems with features of a ciliopathy. Affected individuals typically have some type of intestinal atresia, variable ocular abnormalities, microcephaly, and sometimes involvement of other systems, including renal and cardiac. In some cases, the condition is lethal in early life, whereas other patients show normal survival with or without mild cognitive impairment (summary by Filges et al., 2016).


name: autosomal recessive congenital ichthyosis 9

description: Any autosomal recessive congenital ichthyosis in which the cause of the disease is a mutation in the CERS3 gene.


Joubert syndrome 15

description: Any Joubert syndrome in which the cause of the disease is a mutation in the CEP41 gene.


focal facial dermal dysplasia type IV

description: Focal facial dermal dysplasia type IV (FFDD4) is a rare focal facial dysplasia (FFDD), characterized by congenital isolated preauricular and/or cheek blister scar-like lesions.


cataract 17 multiple types

description: Any early-onset non-syndromic cataract in which the cause of the disease is a mutation in the CRYBB1 gene.


name: delayed sleep phase syndrome, susceptibility to

description: An inherited susceptibility or predisposition to developing delayed sleep phase syndrome.


cataract 20 multiple types

description: Any cataract (disease) in which the cause of the disease is a mutation in the CRYGS gene.


amelogenesis imperfecta type 1B

description: Any amelogenesis imperfecta in which the cause of the disease is a mutation in the ENAM gene.


3M syndrome 3

description: Any 3-M syndrome in which the cause of the disease is a mutation in the CCDC8 gene.


immunodeficiency 19

description: Any severe combined immunodeficiency in which the cause of the disease is a mutation in the CD3D gene.


name: focal segmental glomerulosclerosis 3, susceptibility to

description: Any focal segmental glomerulosclerosis in which the cause of the disease is a mutation in the CD2AP gene.


immunodeficiency 18

description: Immunodeficiency-18 is an autosomal recessive primary immunodeficiency characterized by onset in infancy or early childhood of recurrent infections. Immunologic work-up of the IMD18 SCID patients shows a T cell-negative, B cell-positive, natural killer (NK) cell-positive phenotype, whereas T-cell development is not impaired in the mild form of IMD18.


lymphoproliferative syndrome 2

description: Any lymphoproliferative syndrome in which the cause of the disease is a mutation in the CD27 gene.


cone-rod dystrophy 15

description: Any cone-rod dystrophy in which the cause of the disease is a mutation in the CDHR1 gene.


multiple endocrine neoplasia type 4

description: An autosomal dominant tumor syndrome caused by germline CDKN1B mutations that result in a phenotype similar to that of multiple endocrine neoplasia type 1, characterized by endocrine neoplasms, particularly in the parathyroid glands, pituitary, and pancreas. (WHO 2017)


specific granule deficiency 1

description: Any specific granule deficiency in which the cause of the disease is a mutation in the CEBPE gene.


Seckel syndrome 6

description: Any Seckel syndrome in which the cause of the disease is a mutation in the CEP63 gene.


name: atypical hemolytic-uremic syndrome with B factor anomaly


primary ciliary dyskinesia 14

description: Any primary ciliary dyskinesia in which the cause of the disease is a mutation in the CCDC39 gene.


name: linear skin defects with multiple congenital anomalies 1

description: Any microphthalmia with linear skin defects syndrome in which the cause of the disease is a mutation in the HCCS gene.


name: syndactyly-telecanthus-anogenital and renal malformations syndrome

description: This syndrome is characterized by the association of toe syndactyly, facial dysmorphism including telecanthus (abnormal distance between the eyes) and a broad nasal tip, urogenital malformations and anal atresia.


platelet-type bleeding disorder 10

description: Any inherited bleeding disorder, platelet-type in which the cause of the disease is a mutation in the CD36 gene.


name: coronary heart disease, susceptibility to, 7

description: Any coronary artery disease in which the cause of the disease is a mutation in the CD36 gene.


name: short-rib thoracic dysplasia 13 with or without polydactyly

description: An asphyxiating thoracic dystrophy that has material basis in homozygous mutation in the CEP120 gene on chromosome 5q23.


name: microcephaly 9, primary, autosomal recessive

description: Any autosomal recessive primary microcephaly in which the cause of the disease is a mutation in the CEP152 gene.


Seckel syndrome 5

description: Any Seckel syndrome in which the cause of the disease is a mutation in the CEP152 gene.


name: lissencephaly 7 with cerebellar hypoplasia


Joubert syndrome 5

description: Any Joubert syndrome in which the cause of the disease is a mutation in the CEP290 gene.


Senior-Loken syndrome 6

description: Any Senior-Loken syndrome in which the cause of the disease is a mutation in the CEP290 gene.


Leber congenital amaurosis 10

description: Any Leber congenital amaurosis in which the cause of the disease is a mutation in the CEP290 gene.


Meckel syndrome, type 4

description: Any Meckel syndrome in which the cause of the disease is a mutation in the CEP290 gene.


Bardet-Biedl syndrome 14

description: A Bardet-Biedl syndrome that has material basis in homozygous mutation in the CEP290 gene on chromosome 12q21.


name: retinal dystrophy with or without macular staphyloma


axial spondylometaphyseal dysplasia

description: Axial spondylometaphyseal dysplasia is a genetic disorder of bone growth. The term axial means towards the center of the body. Sphondylos is a Greek term meaning vertebra. Metaphyseal dysplasia refers to abnormalities at the ends of long bones.Axial spondylometaphyseal dysplasia primarily affects the bones of the chest, pelvis, spine,upper arms and upper legs, and results in shortened stature.For reasons not well understood,this rare skeletal dysplasia is also associated withearly and progressivevision loss. The underlying genetic cause of axial spondylometaphyseal dysplasia is currently unknown.It is thought to be inherited in an autosomal recessive fashion.


CHARGE syndrome

description: CHARGE syndrome is a multiple congenital anomaly syndrome characterized by the variable combination of multiple anomalies, mainly Coloboma; Choanal atresia/stenosis; Cranial nerve dysfunction; Characteristic ear anomalies (known as the major 4 C's).


name: scoliosis, isolated, susceptibility to, 3


name: hypogonadotropic hypogonadism 5 with or without anosmia

description: Any hypogonadotropic hypogonadism in which the cause of the disease is a mutation in the CHD7 gene.


name: vitamin D hydroxylation-deficient rickets, type 1B

description: An autosomal recessive form of rickets caused by inactivating mutation(s) in the CYP2R1 gene, encoding vitamin D 25-hydroxylase, the hepatic enzyme that converts vitamin D to 25-hydroxyvitamin D, the precursor of 1,25-dihydroxyvitamin D (calcitriol). The condition is characterized by reduced serum concentrations of 25-hydroxyvitamin D, hypophosphatemia, hypocalcemia with secondary hyperparathyroidism and elevated serum alkaline phosphatase, and by failure to thrive, seizures, muscle weakness, and rickets.


name: carbamoyl phosphate synthetase I deficiency disease

description: Carbamoyl-phosphate synthetase 1 deficiency (CPS1D) is a rare and severe disorder of urea cycle metabolism most commonly characterized by either a neonatal-onset of severe hyperammonemia that occurs few days after birth and manifests with lethargy, vomiting, hypothermia, seizures, coma and death or a presentation outside the newborn period at any age with (sometimes) milder symptoms of hyperammonemia.


name: pulmonary hypertension, neonatal, susceptibility to


name: carnitine palmitoyl transferase II deficiency, myopathic form

description: The myopathic form of carnitine palmitoyltransferase II (CPT II) deficiency, an inherited metabolic disorder that affects mitochondrial oxidation of long chain fatty acids (LCFA), is the most common and the least severe form of CPT II deficiency.


name: carnitine palmitoyl transferase II deficiency, severe infantile form

description: The severe infantile form of carnitine palmitoyltransferase II (CPT II) deficiency, an inherited disorder that affects mitochondrial oxidation of long chain fatty acids (LCFA), is the early-onset form of the disease.


name: carnitine palmitoyl transferase II deficiency, neonatal form

description: The neonatal form of carnitine palmitoyltransferase II (CPT II) deficiency, an inherited disorder that affects mitochondrial oxidation of long chain fatty acids (LCFA), is the lethal form of the disease which presents with multisystem failure.


name: encephalopathy, acute, infection-induced, susceptibility to, 4

description: Any encephalopathy, acute, infection-induced in which the cause of the disease is a mutation in the CPT2 gene.


cataract 39 multiple types

description: Any early-onset non-syndromic cataract in which the cause of the disease is a mutation in the CRYGB gene.


name: autosomal dominant nonsyndromic hearing loss 40

description: Any autosomal dominant nonsyndromic deafness in which the cause of the disease is a mutation in the CRYM gene.


name: neurodegeneration with brain iron accumulation 4

description: Mitochondrial membrane protein-sssociated neurodegeneration (MPAN), also known as neurogeneration with brain iron accumulation (NBIA) due to C19orf12 mutations, is an autosomal recessive neurodegenerative disorder characterized by iron accumulation in specific regions of the brain, usually the basal ganglia, and associated with slowly progressive pyramidal (spasticity) and extrapyramidal (dystonia) signs, motor axonal neuropathy, optic atrophy, cognitive decline, and neuropsychiatric abnormalities.


hereditary spastic paraplegia 43

description: Autosomal recessive spastic paraplegia type 43 is a rare, complex hereditary spastic paraplegia characterized by a childhood to adolescent onset of progressive lower limb spasticity, associated with mild to severe gait disturbances, extensor plantar responses, muscle weakness and severe distal atrophy, frequently with upper limb involvement. Additional features may include joint contractures, distal sensory loss and brisk or absent deep tendon reflexes. Other signs, such as depression, memory loss, optic atrophy (with vision loss) and brain iron deposition (revealed by brain imagery), have also been reported.


Wagner disease

description: Wagner disease is a rare hereditary vitreoretinopathy characterized by an anomaleous vitreous associated with myopia, cataract, chorioretinal atrophy, and peripheral tractional or rhegmatogenous retinal detachment.


hereditary spastic paraplegia 5A

description: Autosomal recessive spastic paraplegia type 5A (SPG5A) is a form of hereditary spastic paraplegia characterized by either a pure phenotype of slowly progressive spastic paraplegia of the lower extremities with bladder dysfunction and pes cavus or a complex presentation with additional manifestations including cerebellar signs, nystagmus, distal or generalized muscle atrophy and cognitive impairment. Age of onset is highly variable, ranging from early childhood to adulthood. White matter hyperintensity and cerebellar and spinal cord atrophy may be noted, on brain magnetic resonance imaging, in some patients.


congenital bile acid synthesis defect 3

description: Congenital bile acid synthesis defect type 3 (BAS defect type 3) is a severe anomaly of bile acid synthesis characterized by severe neonatal cholestatic liver disease.


name: atrioventricular septal defect, susceptibility to, 2

description: Any atrioventricular septal defect in which the cause of the disease is a mutation in the CRELD1 gene.


retinitis pigmentosa 12

description: Any retinitis pigmentosa in which the cause of the disease is a mutation in the CRB1 gene.


Leber congenital amaurosis 8

description: Any Leber congenital amaurosis in which the cause of the disease is a mutation in the CRB1 gene.


name: pigmented paravenous retinochoroidal atrophy

description: Pigmented paravenous retinochoroidal atrophy (PPRCA) is a rare, commonly bilateral and symmetric retinal disease characterized by non-progressive or slowly progressive chorioretinal atrophy, peripapillary pigmentary changes and accumulation of ''bone-corpuscle'' pigmentation along the retinal veins and which is usually asymptomatic or can present with mild blurred vision.


name: systemic lupus erythematosus, susceptibility to, 9

description: Any systemic lupus erythematosus in which the cause of the disease is a mutation in the CR2 gene.


cataract 42

description: Any early-onset non-syndromic cataract in which the cause of the disease is a mutation in the CRYBA2 gene.


name: intellectual disability, autosomal recessive 2

description: Any autosomal recessive non-syndromic intellectual disability in which the cause of the disease is a mutation in the CRBN gene.


name: syndromic X-linked intellectual disability 5

description: X-linked Dandy-Walker malformation with intellectual disability, basal ganglia disease and seizures (XDIBS), or Pettigrew syndrome is a central nervous system malformation characterized by severe intellectual deficit, early hypotonia with progression to spasticity and contractures, choreoathetosis, seizures, dysmorphic face (long face with prominent forehead), and brain imaging abnormalities such as Dandy-Walker malformation, and iron deposition.


name: psoriasis 15, pustular, susceptibility to

description: Any generalized pustular psoriasis in which the cause of the disease is a mutation in the AP1S3 gene.


hereditary spastic paraplegia 50

description: Any hereditary spastic paraplegia in which the cause of the disease is a mutation in the AP4M1 gene.


name: diabetes insipidus, nephrogenic, autosomal


name: short-rib thoracic dysplasia 15 with polydactyly


giant axonal neuropathy 2

description: Any giant axonal neuropathy in which the cause of the disease is a mutation in the DCAF8 gene.


mirror movements 1

description: Any familial congenital mirror movements in which the cause of the disease is a mutation in the DCC gene.


name: gaze palsy, familial horizontal, with progressive scoliosis, 2


name: neuronopathy, distal hereditary motor, type 7B

description: Any neuronopathy, distal hereditary motor in which the cause of the disease is a mutation in the DCTN1 gene.


amyotrophic lateral sclerosis type 1

description: An inherited form of amyotrophic lateral sclerosis, usually inherited in an autosomal dominant pattern, caused by mutation(s) in the SOD1 gene, encoding superoxide dismutase.


Perry syndrome

description: Perry syndrome is a rare inherited neurodegenerative disorder characterized by rapidly progressive early-onset parkinsonism, central hypoventilation, weight loss, insomnia and depression.


name: lissencephaly type 1 due to doublecortin gene mutation

description: Type 1 lissencephaly due to doublecortin (DCX) gene mutations is a semi-dominant X-linked disease characterized by intellectual deficiency and seizures that are more severe in male patients.


myxoid liposarcoma

description: A liposarcoma characterized by the presence of round non-lipogenic primitive mesenchymal cells and small signet ring lipoblasts within a myxoid stoma with a branching vascular pattern. This category includes hypercellular lesions with round cell morphology, formerly known as round cell liposarcoma.


spinocerebellar ataxia type 37

description: Spinocerebellar ataxia type 37 (SCA37) is a subtype of autosomal dominant cerebellar ataxia type 1 (ADCA type 1), characterized by a cerebellar syndrome along with altered vertical eye movements.


name: autosomal recessive limb-girdle muscular dystrophy type 2P

description: Autosomal recessive limb-girdle muscular dystrophy type 2P (LGMD2P) is a form of limb-girdle muscular dystrophy characterized by slowly-progressive mainly proximal muscle weakness presenting in early childhood (with difficulties walking and climbing stairs) and mild to severe intellectual disability. Additional manifestations reported include microcephaly, mild increase in thigh or calf muscles, and contractures of the ankles.


name: muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9


familial porphyria cutanea tarda

description: An instance of porphyria cutanea tarda that is caused by an inherited modification of the individual's genome.


pentosuria

description: Pentosuria is an inborn error of metabolism which is characterized by the excretion of 1 to 4 g of the pentose L-xylulose in the urine per day.


xeroderma pigmentosum group E

description: An autosomal recessive genetic disorder caused by mutations in the DDB2 gene. This disease exhibits the mildest degree of sun sensitivity of all xeroderma pigmentosum complementation groups, although individuals are at high risk for skin cancer.


hereditary spastic paraplegia 54

description: A rare, complex form of hereditary spastic paraplegia characterized by the onset in early childhood of progressive spastic paraplegia associated with cerebellar signs, short stature, delayed psychomotor development, intellectual disability and, less commonly, foot contractures, dysarthria, dysphagia, strabismus and optic hypoplasia. SPG54 is caused by mutations in the DDHD2 gene (8p11.23) encoding phospholipase DDHD2.


name: aromatic L-amino acid decarboxylase deficiency

description: Aromatic L-amino acid decarboxylase deficiency is a very rare, severe, genetic neurometabolic disorder associated with clinical manifestations related to underproduction of serotonin and dopamine, mainly hypotonia, hypokinesia, ptosis oculogyric crises, and signs of autonomic dysfunction.


Singleton-Merten syndrome 2

description: Any singleton-Merten dysplasia in which the cause of the disease is a mutation in the DDX58 gene.


name: epilepsy, familial focal, with variable foci 1

description: Any epilepsy, familial focal, with variable foci in which the cause of the disease is a mutation in the DEPDC5 gene.


name: MYELOPROLIFERATIVE/LYMPHOPROLIFERATIVE NEOPLASMS, FAMILIAL (MULTIPLE TYPES), SUSCEPTIBILITY TO


name: developmental and epileptic encephalopathy, 65

description: An autosomal dominant form of developmental and epileptic encephalopathy, caused by mutation(s) in the CYFIP2 gene, encoding cytoplasmic FMR1-interacting protein 2.


ACys amyloidosis

description: Hereditary cerebral hemorrhage with amyloidosis (HCHWA), Icelandic type is a form of HCHWA characterized by an age of onset of 20-30 years, systemic amyloidosis and recurrent lobar intracerebral hemorrhages.


age related macular degeneration 11

description: Any age-related macular degeneration in which the cause of the disease is a mutation in the CST3 gene.


primary ciliary dyskinesia 25

description: Any primary ciliary dyskinesia in which the cause of the disease is a mutation in the DNAAF4 gene.


primary ciliary dyskinesia 18

description: Any primary ciliary dyskinesia in which the cause of the disease is a mutation in the DNAAF5 gene.


primary ciliary dyskinesia 2

description: Any primary ciliary dyskinesia in which the cause of the disease is a mutation in the DNAAF3 gene.


spermatogenic failure 9

description: Any azoospermia in which the cause of the disease is a mutation in the DPY19L2 gene.


primary ciliary dyskinesia 1

description: Any primary ciliary dyskinesia in which the cause of the disease is a mutation in the DNAI1 gene.


episodic ataxia type 6

description: Episodic ataxia type 6 (EA6) is an exceedingly rare form of hereditary episodic ataxia with varying degrees of ataxia and associated findings including slurred speech, headache, confusion and hemiplegia.


name: developmental and epileptic encephalopathy, 41

description: Any early infantile epileptic encephalopathy in which the cause of the disease is a mutation in the SLC1A2 gene.


X-linked chondrodysplasia punctata 2

description: A rare genodermatosis with great phenotypic variation and characterized most commonly by ichthyosis, chondrodysplasia punctata (CDP), asymmetric shortening of the limbs, cataracts and short stature.


lipoid proteinosis

description: Lipoid proteinosis (LP) is a rare genodermatosis characterized clinically by mucocutaneous lesions, hoarseness developing in early childhood and, at times, neurological complications.


description: Moyamoya disease with early-onset achalasia is an exceedingly rare autosomal recessive neurological disorder reported only in a few families so far. It is characterized by the association of early onset achalasia (manifesting in infancy) with severe intracranial angiopathy that is consistent with moyamoya angiopathy in most cases (moyamoya disease). Other variable associated manifestations include hypertension, Raynaud phenomenon, and livedo reticularis.


myostatin-related muscle hypertrophy

description: Myostatin-related muscle hypertrophy is a rare condition characterized by reduced body fat and increased muscle size. Affected individuals have up to twice the usual amount of muscle mass in their bodies. They also tend to have increased muscle strength. This condition is not known to cause any medical problems, and affected individuals are intellectually normal. Myostatin-related muscle hypertrophy is caused by mutations in the MSTN gene. It follows an incomplete autosomal dominant pattern of inheritance.


nephrotic syndrome, type 8

description: Any nephrotic syndrome in which the cause of the disease is a mutation in the ARHGDIA gene.


Shwachman-Diamond syndrome 2

description: Shwachman-Diamond syndrome-2 (SDS2) is characterized by exocrine pancreatic dysfunction, hematopoietic abnormalities, short stature, and metaphyseal dysplasia ({1:Stepensky et al., 2017}).nnFor a discussion of genetic heterogeneity of Shwachman-Diamond syndrome, see SDS1 (OMIM:260400).


Meier-Gorlin syndrome 6

description: Any Meier-Gorlin syndrome in which the cause of the disease is a mutation in the GMNN gene.


congenital myasthenic syndrome 12

description: Any congenital myasthenic syndromes with glycosylation defect in which the cause of the disease is a mutation in the GFPT1 gene.


name: fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3

description: Combined oxidative phosphorylation deficiency type 3 is an extremely rare clinically heterogenous disorder described in about 5 patients to date. Clinical signs included hypotonia, lactic acidosis, and hepatic insufficiency, with progressive encephalomyopathy or hypertrophic cardiomyopathy.


description: Gamma-glutamyl transpeptidase deficiency is characterized by increased glutathione concentration in the plasma and urine.


name: developmental and epileptic encephalopathy, 3

description: Any early infantile epileptic encephalopathy in which the cause of the disease is a mutation in the SLC25A22 gene.


anterior segment dysgenesis 7

description: Any anterior segment dysgenesis in which the cause of the disease is a mutation in the PXDN gene.


postaxial acrofacial dysostosis

description: Postaxial acrofacial dysostosis (POADS) is a type of acrofacial dysostosis characterized by mandibular and malar hypoplasia, small and cup-shaped ears, lower lid ectropion, and symmetrical postaxial limb deficiencies with absence of the fifth digital ray and ulnar hypoplasia.


name: severe combined immunodeficiency due to CTPS1 deficiency

description: Severe combined immunodeficiency (SCID) due to CTPS1 deficiency is a rare primary immunodeficiency disorder due to impaired capacity of activated T- and B-cells to proliferate in response to antigen receptor-mediated activation characterized by early-onset, severe, persistent and/or recurrent viral infections due to Epstein-Barr virus (EBV) and Varicella Zoster virus (VZV), (including generalized varicella), as well as recurrent sino-pulmonary bacterial infections due to encapsulated pathogens.


name: developmental and epileptic encephalopathy, 50

description: An autosomal recessive form of early infantile epileptic encephalopathy, caused by mutation(s) in the CAD gene, encoding CAD protein.


glycogen storage disease V

description: Myophosphorylase deficiency (McArdle's disease), or glycogen storage disease type 5 (GSD5), is a severe form of glycogen storage disease characterized by exercise intolerance.


myofibrillar myopathy 8

description: Any myofibrillar myopathy in which the cause of the disease is a mutation in the PYROXD1 gene.


name: mitochondrial complex III deficiency nuclear type 4

description: Any mitochondrial complex III deficiency in which the cause of the disease is a mutation in the UQCRQ gene.


name: proteasome-associated autoinflammatory syndrome 3


essential hypertension

description: Hypertension that presents without an identifiable cause.


name: metaphyseal chondrodysplasia, Jansen type

description: Jansen's metaphyseal chondrodysplasia (JMC) is a very rare autosomal dominant skeletal dysplasia characterized by short-limbed short stature (due to severe metaphyseal changes that are often discovered in childhood by imaging), waddling gait, bowed legs, contracture deformities of the joints, short hands with clubbed fingers, clinodactyly, prominent upper face and small mandible, as well as chronic parathyroid hormone-independent hypercalcemia, hypercalciuria, and mild hypophosphatemia.


chondrodysplasia Blomstrand type

description: Blomstrand lethal chondrodysplasia (BLC) is a neonatal osteosclerotic dysplasia characterized by advanced endochondral bone maturation, very short limbs, dwarfism and prenatal lethality.


Ollier disease

description: A rare primary bone dysplasia disorder characterized by the development of multiple mainly unilateral or asymmetrically distributed enchondromas throughout the metaphyses of the long bones.


Eiken syndrome

description: Eiken syndrome is a rare familial skeletal dysplasia characterized by multiple epiphyseal dysplasia, with extremely retarded ossification. It has been described in 6 members of a unique consanguineous family.


brachydactyly type E2

description: Any brachydactyly type E in which the cause of the disease is a mutation in the PTHLH gene.


LEOPARD syndrome 1

description: Any Noonan syndrome with multiple lentigines in which the cause of the disease is a heterozygous mutation in the PTPN11 gene on chromosome 12q24.


Noonan syndrome 1

description: Noonan syndrome caused by mutations in the PTPN11 gene.


juvenile myelomonocytic leukemia

description: A myelodysplastic/myeloproliferative neoplasm of childhood that is characterized by proliferation principally of the granulocytic and monocytic lineages. Myelomonocytic proliferation is seen in the bone marrow and the blood. The leukemic cells may infiltrate any tissue, however liver, spleen, lymph nodes, skin, and respiratory tract are the most common sites of involvement. (WHO, 2001)


metachondromatosis

description: Metachondromatosis (MC) is a rare disorder characterized by the presence of both multiple enchondromas and osteochondroma-like lesions.


BH4-deficient hyperphenylalaninemia A

description: An autosomal recessive condition caused by mutation(s) in the PTS gene, encoding 6-pyruvoyl tetrahydrobiopterin synthase. It is characterized by BH4-defecient hyperphenylalanemia, depletion of dopamine and serotonin, and progressive cognitive and motor deficits.