A lipodystrophy characterized by the association of lipoatrophy, hypertriglyceridemia, hepatomegaly and acromegaloid features. BSCL belongs to the group of extreme insulin resistance syndromes, which also includes leprechaunism, Rabson-Mendenhall syndrome, acquired generalized lipodystrophy, and types A and B insulin resistance.


hereditary spastic paraplegia 46

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

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.


Löfgren syndrome

A sarcoidosis characterized by the triad of erythema nodosum, bilateral hilar lymphadenopathy on chest radiograph, and joint pain.


tendon sheath disorder

A disease that involves the tendon sheath.


autosomal dominant nonsyndromic hearing loss 3A

Any autosomal dominant nonsyndromic deafness in which the cause of the disease is a mutation in the GJB2 gene.


dysbaric osteonecrosis

A form of avascular necrosis where there is death of a portion of the bone that is thought to be caused by nitrogen embolism.


frontofacionasal dysplasia

Fronto-facio-nasal dysostosis is characterized by multiple craniofacial anomalies (brachycephaly, blepharophimosis, ptosis, S-shaped palpebral fissures, coloboma, cleft lip and palate, deformed nostrils, encephalocele, hypertelorism, midface hypoplasia, malformed eyes, and absent inner eyelashes).


autosomal recessive distal osteolysis syndrome

Autosomal recessive distal osteolysis syndrome is an early-onset distal osteolysis characterized by severe resorption of the hands and feet and absence of the distal and middle phalanges. It has been described in a son and daughter born to consanguineous parents. Other manifestations include distal muscular hypertrophy, flexion contractures, short stature, mild intellectual deficit and characteristic facies (maxillary hypoplasia, exophthalmos, and a broad nasal tip). It is transmitted as an autosomal recessive trait.


dedifferentiated solitary fibrous tumor

A solitary fibrous tumor characterized by the presence of areas of abrupt transition to high grade sarcoma.


neuronopathy, distal hereditary motor, type 2D

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


developmental and epileptic encephalopathy, 60


qualitative or quantitative defects of telethonin


partial duplication of the long arm of chromosome 7

Chromosome 7q duplication is a chromosome abnormality that occurs when there is an extra copy of genetic material on the long arm (q) of chromosome 7. The severity of the condition and the signs and symptoms depend on the size and location of the duplication and which genes are involved. Features that often occur in people with chromosome 7q duplication include developmental delay, intellectual disability, behavioral problems and distinctive facial features. Most cases are not inherited, but people can pass the duplication on to their children. Treatment is based on the signs and symptoms present in each person.


myoclonic encephalopathy in non-progressive disorder

This group of epilepsies are typically is characterized by onset of seizures from day 1 of life to 5 years (peak 12 months). Both sexes are affected, however the male to female ratio is 1:2. Antecedent (including birth) history, head size, neurological and developmental findings reflect the underlying cause (if known). Myoclonic status epilepticus is often the initial presenting seizure type, however other initial seizure types may also occur. Prognosis is unfavorable with severe neurological and developmental impairments typically seen.


nerve root neoplasm

Benign and malignant neoplasms arising from one or more of the cervical, thoracic, lumbar, sacral, or coccygeal nerve roots. The majority of these tumors are benign. Clinical manifestations may include pain, weakness and loss of sensation along the course of the involved nerve root. Large tumors may cause spinal cord compression.


toxic or nutritional optic neuropathy

A disease with basis in optic nerve damage secondary to a toxic substance and/or nutritional deficiency.


leishmaniasis

Infectious disease that is transmitted through the bite of hematophagous female phlebotomine sand flies. The clinical spectrum ranges from asymptomatic to clinically overt disease which can remain localized to the skin or disseminate to the upper oral and respiratory mucous membranes or throughout the reticulo-endothelial system. Three main clinical syndromes have been described: visceral (or Kala-Azar; with fever, weight loss, hepatosplenomegaly), cutaneous, and mucocutaneous leishmaniasis (cutaneous or mucocutaneous ulceration).


transient congenital hypothyroidism due to neonatal factor


hereditary sensory and autonomic neuropathy type 6

Any hereditary sensory and autonomic neuropathy in which the cause of the disease is a mutation in the DST gene.


classic Hodgkin lymphoma, nodular sclerosis type


skin fragility-woolly hair-palmoplantar keratoderma syndrome


2-methylacetoacetyl CoA thiolase deficiency


capillary disorder

A disease involving a capillary.


Hodgkin's lymphoma, mixed cellularity

A subtype of classical Hodgkin lymphoma with scattered Reed-Sternberg and Hodgkin cells in a diffuse or vaguely nodular mixed inflammatory background without nodular sclerosing fibrosis. (WHO, 2008)


spinocerebellar ataxia type 17

A rare subtype of type I autosomal dominant cerebellar ataxia (ADCA type I). It is characterized by a variable clinical picture which can include dementia, psychiatric disorders, parkinsonism, dystonia, chorea, spasticity, and epilepsy.


epulis

A non-neoplastic nodular lesion that arises from the gingiva.


neurodevelopmental disorder with intracranial hemorrhage, seizures, and spasticity


atypical glycine encephalopathy

Atypical glycine encephalopathy is a rare form of glycine encephalopathy (GE) presenting disease onset or clinical manifestations that differ from neonatal or infantile GE.


prostate leiomyosarcoma

An aggressive malignant smooth muscle neoplasm, arising from the prostate. It is characterized by a proliferation of neoplastic spindle cells.


glycogen storage disease due to glycogen branching enzyme deficiency, adult neuromuscular form


craniotelencephalic dysplasia

Craniotelencephalic dysplasia is an extremely rare, genetic developmental defect during embryogenesis syndrome characterized by craniosynostosis with frontal encephalocele and various additional brain anomalies (severe hydrocephalus, agenesis of the corpus callosum, lissencephaly and polymicrogyria, parenchymal cysts, septo-optic dysplasia) resulting in marked cerebral dysfunction, seizures and very severe psychomotor delay. There have been no further descriptions in the literature since 1983.


wet macular degeneration

A form of RETINAL degeneration in which abnormal CHOROIDAL NEOVASCULARIZATION occurs under the RETINA and MACULA LUTEA, causing bleeding and leaking of fluid. This leads to bulging and or lifting of the macula and the distortion or destruction of central vision.


nemaline myopathy

Nemaline myopathy (NM) encompasses a large spectrum of myopathies characterized by hypotonia, weakness and depressed or absent deep tendon reflexes, with pathologic evidence of nemaline bodies (rods) on muscle biopsy.


petroclival meningioma

A meningioma that affects the petroclival region.


dendritic cell tumor

A dendritic cell tumor develops from the cells of the immune system. This condition typically begins in the lymph system and may spread to nearby organs or distant parts of the body (metastasize). There are five subtypes of dendritic cell tumors: follicular dendritic cell tumor, interdigitating dendritic cell tumor, Langerhans' cell histiocytosis, Langerhans' cell sarcoma, and dendritic cell sarcoma not specified otherwise. The symptoms and severity of the condition depend on the subtype and location of the tumor. Treatment may include surgery, radiation therapy, and/or chemotherapy.


ataxia - telangiectasia variant

Ataxia-telangiectasia variant is a rare, genetic, persistent combined dystonia characterized by clinical signs similar to ataxia-telangiectasia but with a later (usually adulthood) onset and slower progression. Patients typically present extrapyramidal signs, such as resting tremor, choreathetosis, and dystonia, as the initial symptoms and later often develop mild cerebellar ataxia (with gait usually preserved). Telangiectasia and immunodeficiency may be absent but secondary features of ataxia-telangiectasia, such as risk of malignancy, dysarthria and peripheral neuropathy, are frequently present.


intellectual developmental disorder, autosomal dominant 65


autosomal recessive nonsyndromic hearing loss 20

An autosomal recessive nonsyndromic deafness that has material basis in variation in the chromosome region 11q25-qter.


hypercholesterolemia due to cholesterol 7alpha-hydroxylase deficiency


Dandy-Walker malformation-postaxial polydactyly syndrome

Dandy-Walker malformation with postaxial polydactyly syndrome is a syndromic disorder with, as a major feature, the association between Dandy-Walker malformation and postaxial polydactyly. The Dandy-Walker malformation has a variable expression and is characterized by a posterior fossa cyst communicating with the fourth ventricle, the partial or complete absence of the cerebellar vermis, and facultative hydrocephalus. Postaxial polydactyly includes tetramelic postaxial polydactyly of hands and feet with possible enlargement of the fifth metacarpal and metatarsal bones, as well as bifid fifth metacarpals.


monoclonal paraproteinemia disease

A disease characterized by the presence of excessive amounts of paraprotein or single monoclonal gammaglobulin in the blood. It is usually due to an underlying immunoproliferative disorder or hematologic neoplasms, especially multiple myeloma.


benign neoplasm of choroid

A benign neoplasm that involves the optic choroid.


intravascular papillary endothelial hyperplasia

A reactive, well-circumscribed vascular lesion. It is characterized by the formation of thin papillae projecting within the lumen of blood vessels. The papillae are lined by plump endothelial cells. Blood clots are also present.


malignant soft tissue neoplasm

A malignant neoplasm arising exclusively from the soft tissues.


metaphyseal dysostosis-intellectual disability-conductive deafness syndrome

Metaphyseal dysostosis-intellectual disability-conductive deafness syndrome is characterized by metaphyseal dysplasia, short-limb dwarfism, mild intellectual deficit and conductive hearing loss, associated with repeated episodes of otitis media in childhood. It has been described in three brothers born to consanguineous Sicilian parents. Variable manifestations included hyperopia and strabismus. The mode of inheritance is autosomal recessive.


fetal akinesia-cerebral and retinal hemorrhage syndrome

Fetal akinesia-cerebral and retinal hemorrhage syndrome is a rare, lethal, congenital myopathy syndrome characterized by decreased fetal movements and polyhydraminos in utero and the presence of akinesia, severe hypotonia with respiratory insufficiency, absent reflexes, joint contractures, skeletal abnormalities with thin ribs and bones, intracranial and retinal hemorrhages and decreased birth weight in the neonate.


progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 5

Any progressive external ophthalmoplegia with mitochondrial DNA deletions in which the cause of the disease is a mutation in the RRM2B gene.


infectious meningitis

Inflammation of the meninges of the brain and/or spinal cord caused by an infectious agent (viral, bacterial, or fungal). Symptoms include headache, fever, vomiting, neck stiffness, photophobia, confusion, and seizures.


skin disorder caused by infection

Skin diseases caused by bacteria, fungi, parasites, or viruses.


cap myopathy

Cap myopathy is a very rare congenital myopathy presenting a weakness of facial and respiratory muscles associated with craniofacial and thoracic deformities, as well as weakness of limb proximal and distal muscles. Onset is at birth or in childhood, weakness progression is slow but may lead to a severe and even fatal prognosis.


spinal muscular atrophy, facioscapulohumeral type


mesoblastic nephroma

A solid, unencapsulated tumor of the kidney composed of spindle mesenchymal cells that resemble fibroblasts or muscle cells. The homogeneous mass typically extends into the renal parenchyma and replaces most of the kidney. In most cases, mesoblastic nephroma is benign and occurs in the fetus or newborn, and rarely in the older child or the adult.


broad ligament malignant neoplasm

A malignant neoplasm involving the broad ligament of uterus.


mammary-digital-nail syndrome

Mammary-digital-nail syndrome is a syndromic limb malformation characterized by congenital onychodystrophy/anonychia, brachydactyly of the fifth finger, digitalization of the thumbs, with absence or hypoplasia of the distal phalanges of the hands and feet in association with juvenile hypertrophy of the breast with gigantomastia in peripubertal females.


neurological muscular channelopathy due to a genetic potassium channel defect


leiomyoma

A well-circumscribed benign smooth muscle neoplasm characterized by the presence of spindle cells with cigar-shaped nuclei, interlacing fascicles, and a whorled pattern.


optic atrophy with demyelinating disease of CNS


corneal-cerebellar syndrome

A rare, genetic, neurological disorder characterized by the association of slowly progressive spinocerebellar degeneration and corneal dystrophy, manifesting with bilateral corneal opacities (which lead to severe visual impairment), mild intellectual disability, ataxia, gait disturbances, and tremor. Additional manifestations include facial dysmorphism (i.e. triangular face, ptosis, low-set, posteriorly angulated ears, and micrognathia), as well as mild upper motor neuron involvement with hypertonia, lower limb hyperreflexia and extensor plantar responses. There have been no further descriptions in the literature since 1985.


toxemia of pregnancy

A pregnancy induced hypertensive state that occurs after 20 weeks of gestation characterized by an increase in blood pressure, along with body swelling and proteinuria.


nephrotic syndrome, type 6

Any nephrotic syndrome in which the cause of the disease is a mutation in the PTPRO gene.


glycosylphosphatidylinositol biosynthesis defect 15

A rare, genetic, syndromic intellectual disability characterized by global developmental delay, early-onset seizures, cerebellar atrophy, osteopenia, nystagmus and dysmorphic facial features, including bitemporal narrowing, prominent forehead, anteverted nares. Dysarthria, dysmetria, ataxic gait, spasticity and dysmorphic features have also been associated.


developmental and epileptic encephalopathy, 45

Any early infantile epileptic encephalopathy in which the cause of the disease is a mutation in the GABRB1 gene.


pulmonary valve agenesis-tetralogy of fallot-absence of ductus arteriosus syndrome

Pulmonary valve agenesis-tetralogy of Fallot-absence of ductus arteriosus syndrome is a rare congenital heart malformation characterized by a tetralogy of Fallot (pulmonary stenosis, overriding aorta, ventricular septal defect and right ventricular hypertrophy), complete absence or rudimentary pulmonary valve that is both stenotic and regurgitant and an absence of the ductus arteriosus. It presents prenatally with cardiomegaly, polyhydramnios, fetal heart failure, hydrops fetalis and fetal demise or postnatally with cyanosis and respiratory failure due to bronchomalacia secondary to bronchial compression from dilated pulmonary arteries. It is frequently associated with 22q11 deletion.


progressive retinal dystrophy due to retinol transport defect


myopathy, lactic acidosis, and sideroblastic anemia 1

Any myopathy, lactic acidosis, and sideroblastic anemia in which the cause of the disease is a mutation in the PUS1 gene.


3M syndrome 1

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


skeletal muscle neoplasm

A benign or malignant mesenchymal neoplasm arising from skeletal muscle.


carbohydrate metabolism disease

A disease that has its basis in the disruption of carbohydrate metabolic process.


16p13.11 microdeletion syndrome

16p13.11 microdeletion syndrome is a recently described syndrome characterized by developmental delay, microcephaly, epilepsy, short stature, facial dysmorphism and behavioral problems.


adult lymphoma

A lymphoma that occurs in an adult.


posthitis

An inflammatory disease involving a pathogenic inflammatory response in the prepuce of penis.


telangiectatic osteogenic sarcoma

An osteosarcoma usually arising from the metaphysis of long bones. It is characterized by the presence of a cystic architecture with blood-filled spaces. The prognosis is similar to that of conventional osteosarcoma.


dermatitis herpetiformis, familial

Dermatitis herpetiformis is a rare, chronic, skin disorder characterized by groups of severely itchy blisters and raised skin lesions. These are more common on the knees, elbows, buttocks and shoulder blades. The slow onset of symptoms usually begins during adulthood, but children can also be affected. Other symptoms mayinclude fluid-filled sores; red lesions that resemble hives; and itchiness, rednessand burning. The exact cause of this disease is not known,but it is frequently associated with the inability to digest gluten. People with this disease are typically treated with the drug dapsone.


dental pulp necrosis

Death of pulp tissue with or without bacterial invasion. When the necrosis is due to ischemia with superimposed bacterial infection, it is referred to as pulp gangrene. When the necrosis is non-bacterial in origin, it is called pulp mummification.


congenital myopathy 4B, autosomal recessive

Any congenital myopathy in which the cause of the disease is a mutation in the TPM3 gene.


Hartnup disease

Hartnup disease is a rare metabolic disorder belonging to the neutral aminoacidurias and characterized by abnormal renal and gastrointestinal transport of neutral amino acids (tryptophan, alanine, asparagine, glutamine, histidine, isoleucine, leucine, phenylalanine, serine, threonine, tyrosine and valine).


melanocytic neoplasm

A benign or malignant, primary or metastatic neoplasm affecting the melanocytes.


developmental and epileptic encephalopathy 105 with hypopituitarism


sweat gland cancer

A malignant neoplasm that affects the sweat glands.


monosomy chromosome 8

A chromosomal disorder consisting of the absence of one chromosome 8.


malignant dermis tumor

A malignant neoplasm involving the dermis.


necrotizing encephalomyelopathy, subacute, of Leigh, adult


ASAH1-related sphingolipidosis

A spectrum of disorders that includes Farber disease and spinal muscular atrophy with progressive myoclonic epilepsy. Both disorders are caused by mutations in the ASAH1 gene that encodes the lysosomal hydrolase that breaks down the bioactive lipid, ceramide.


glycogen storage disease due to glycogen branching enzyme deficiency, congenital neuromuscular form


carbohydrate transport disease

A disease that has its basis in the disruption of carbohydrate transport.


unilateral retinoblastoma

A retinoblastoma that only involves a single eye.


mixed cell uveal melanoma

A melanoma arising from the choroid, ciliary body, or the iris. It is characterized by the presence of a mixture of spindle A melanoma cells, spindle B melanoma cells, and epithelioid melanoma cells.


autosomal dominant nonsyndromic hearing loss 53

An autosomal dominant nonsyndromic deafness that has material basis in variation in the chromosome region 14q11.2-q12.


congenital insensitivity to pain-hypohidrosis syndrome

A hereditary sensory neuropathy characterized by congenital insensitivity to pain and decreased sweating and tear production that has material basis in homozygous mutation in the PRDM12 gene on chromosome 9q34.


microphthalmia, isolated, with coloboma 6


hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism

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


autosomal dominant spondylocostal dysostosis

Autosomal dominant spondylocostal dysostosis is a very rare and mild form of spondylocostal dysostosis characterized by vertebral and costal segmentation defects, often with a reduction in the number of ribs.


hereditary spastic paraplegia 77

Autosomal recessive spastic paraplegia type 77 is a rare, pure or complex hereditary spastic paraplegia characterized by an infancy to childhood onset of slowly progressive lower limb spasticity, delayed motor milestones, gait disturbances, hyperreflexia and various muscle abnormalities, including weakness, hypotonia, intention tremor and amyotrophy. Ocular abnormalities (e.g. strabismus, ptosis) and other neurological abnormalities, such as dysarthria, seizures and extensor plantar responses, may also be associated.


autoimmune lymphoproliferative syndrome, type III caused by mutation in PRKCD

Any autoimmune lymphoproliferative syndrome in which the cause of the disease is a mutation in the PRKCD gene.


hereditary spastic paraplegia 6

Autosomal dominant spastic paraplegia type 6 (SPG6) is a form of hereditary spastic paraplegia which usually presents in late adolescence or early adulthood as a pure phenotype of lower limb spasticity with hyperreflexia and extensor plantar responses, as well as mild bladder disturbances and pes cavus. Rarely, it can present as a complex phenotype with additional manifestations including epilepsy, variable peripheral neuropathy and/or memory impairment.


angular blepharoconjunctivitis

A blepharoconjunctivitis that is characterized by fissuring, scaling, maceration and erythema of the lateral or medial canthal area.


disorder of folate metabolism and transport


coenzyme Q10 deficiency

A genetically heterogeneous condition, typically inherited in an autosomal recessive fashion, characterized by coenzyme Q10 deficiency.


Angelman syndrome due to paternal uniparental disomy of chromosome 15


hereditary spastic paraplegia 39

This syndrome is characterized by progressive spastic paraplegia and distal muscle wasting.


acquired kinky hair syndrome

Acquired progressive kinking of the hair (APKH) is a rare hair disorder characterized by the appearance of lustreless, curly, frizzy, and coarse hair generally during adolescence predominantly in the frontal, temporal, and vertex regions of the scalp. Eyelashes, as well as growth and pigmentation of the hair, may also be affected.


peroxisome biogenesis disorder 13A (Zellweger)


thrombophilia due to protein C deficiency, autosomal recessive


autosomal recessive nonsyndromic hearing loss 1B

Any autosomal recessive nonsyndromic deafness in which the cause of the disease is a mutation in the GJB6 gene.


limbic encephalitis with DPP6 antibodies


hypogonadotropic hypogonadism-severe microcephaly-sensorineural hearing loss-dysmorphism syndrome


linear skin defects with multiple congenital anomalies 2

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


split hand, bilateral

Split hand, bilateral is a rare, non-syndromic limb reduction defect, clinically and genetically heterogeneous, characterized by bilateral underdevelopment or absence of the central rays of the autopod, with absence of all, or just some, of the central phalanges and at least part of the associated metacarpal bones, yielding a cleft appearance of the hand. It is frequently associated with syndactyly and aplasia/hypoplasia of remaining digits and metacarpal bones. No other dysmorphic features are observed and development is appropriate for age.


pontocerebellar hypoplasia, type 1C

Any pontocerebellar hypoplasia type 1 in which the cause of the disease is a mutation in the EXOSC8 gene.


developmental and epileptic encephalopathy, 21

Any early infantile epileptic encephalopathy in which the cause of the disease is a mutation in the NECAP1 gene.


autosomal recessive nonsyndromic hearing loss 93

Any autosomal recessive nonsyndromic deafness in which the cause of the disease is a mutation in the CABP2 gene.


Baraitser-winter syndrome 2

Any Baraitser-Winter cerebrofrontofacial syndrome in which the cause of the disease is a mutation in the ACTG1 gene.


arbovirus infection

A viral infection that is transmitted by an arthropod.


facial onset sensory and motor neuronopathy

Facial onset sensory and motor neuronopathy is characterized initially by paraesthesia and numbness in the region of the trigeminal nerve distribution, which later progresses to involve the scalp, neck, upper trunk and upper limbs. Onset of motor manifestations occurs later with cramps, fasciculations, dysphagia, dysarthria, muscle weakness and atrophy. This syndrome has been described in four males and appears to be a slowly progressive neurodegenerative disease.


hypogonadotropic hypogonadism 12 with or without anosmia

A hypogonadotropic hypogonadism that has material basis in homozygous mutation in the GNRH1 gene on chromosome 8p21.


holoprosencephaly 9

Any holoprosencephaly in which the cause of the disease is a mutation in the GLI2 gene.


B-lymphoblastic leukemia/lymphoma with t(17;19)


tuberculous pneumothorax

A pneumothorax in which air enters into the pleural cavity.


hereditary spastic paraplegia 57

An extremely rare, complex type of hereditary spastic paraplegia, characterized by onset in infancy of pronounced leg spasticity (leading to the inability to walk independently), reduced visual acuity due to optic atrophy, and distal wasting of the hands and feet due to an axonal demyelinating sensorimotor neuropathy. SPG57 is caused by mutations in the TFG gene (3q12.2) encoding protein TFG, which is thought to play a role in ER microtubular architecture and function.


craniometadiaphyseal dysplasia, wormian bone type

Craniometadiaphyseal dysplasia, wormian bone type is an extremely rare craniotubular bone dysplasia syndrome described in fewer than 10 patients to date. Clinical manifestations include macrocephaly, frontal bossing, malar hypoplasia, prominent mandible and dental hypoplasia. Other skeletal anomalies include abnormal bone modeling in tubular bones, multiple wormian bones and deformities of chest, pelvis and elbows. An increased risk of fractures is noted.


benign neoplasm of parathyroid gland

A benign neoplasm that involves the parathyroid gland.


late-onset localized junctional epidermolysis bullosa-intellectual disability syndrome


rheumatic heart disease

An autoinflammatory condition following an infection with Group A Beta Hemolytic Streptococcus (GABHS), in which the heart is attacked by antibodies formed in reaction to a recent GABHS infection. Chief anatomic changes of the valve include leaflet thickening, commissural fusion, and shortening and thickening of the tendinous cords, all of which can result in valvular dysfunction.


paternal uniparental disomy of chromosome 20

Paternal uniparental disomy of chromosome 20 is a very rare chromosomal anomaly in which both copies of chromosome 20 are inherited from the father. The main features described are high birth weight and/or early-onset obesity, relative macrocephaly, and tall stature. Most patients were ascertained during sporadic pseudohypoparathyroidism type 1b testing and have UPD involving variable segments of the long arm of chromosome 20.


cornea plana 2

Any cornea plana in which the cause of the disease is a mutation in the KERA gene.


schizophrenia 15

A schizophrenia that has material basis in a mutation of SHANK3 on chromosome 22q13.33.


spondyloepimetaphyseal dysplasia, Guo-Campeau type


traumatic brain injury

A brain disease that is characterized by brain dysfunction caused by an outside force, usually a violent blow to the head.


middle cranial fossa meningioma

A meningioma that affects the middle cranial fossa.


cyclothymic disorder

An affective disorder characterized by periods of depression and hypomania. These may be separated by periods of normal mood.


neurodevelopmental disorder with language delay and behavioral abnormalities, with or without seizures


cutaneous collagenous vasculopathy

Cutaneous collagenous vasculopathy (CCV) is a primary microangiopathy confined to the skin, characterized by multiple and widespread telangiectasias.


Alzheimer disease 11

An Alzheimer's disease that is characterized by an associated with variation in the region 9p22.1.


nonsyndromic genetic hearing loss

A disease characterized by hearing loss that is not part of a larger syndrome.


benign lymphoepithelial lesion of salivary gland

A benign lesion that involves the salivary glands, usually the parotid gland. It affects females more often than males and it may be a manifestation of autoimmune diseases such as Sjogren syndrome. There is an increased incidence of benign lymphoepithelial lesions in HIV-positive patients. It is characterized by the presence of a marked lymphocytic infiltrate and epi-myoepithelial islands in the affected salivary gland. Patients usually present with firm and painless swelling of the affected salivary gland. There is an increased risk for development of lymphoma.


neoplasm of mature T-cells or NK-cells

A group of neoplasms composed of T-lymphocytes with a mature (peripheral/post-thymic) immunophenotypic profile and/or NK-cells.


hereditary hyperekplexia

Hereditary hyperekplexia is a hereditary neurological disorder characterized by excessive startle responses.


benign carotid body paraganglioma

A carotid body paraganglioma that is confined to the site of origin, without metastatic potential.


angiodysplasia

Acquired degenerative dilation or expansion (ectasia) of normal blood vessels, often associated with aging. They are isolated, tortuous, thin-walled vessels and sources of bleeding. They occur most often in mucosal capillaries of the gastrointestinal tract leading to gastrointestinal hemorrhage and anemia.


combined oxidative phosphorylation deficiency 54


juvenile idiopathic scoliosis

A scoliosis with no known cause arising in a juvenile.


inborn disorder of ornithine or proline metabolism


agammaglobulinemia 6, autosomal recessive

Any autosomal agammaglobulinemia in which the cause of the disease is a mutation in the CD79B gene.


GAPO syndrome

A multiple congenital anomalies (MCA) syndrome involving connective tissue characterized by growth retardation, alopecia, pseudoanodontia and ocular manifestations


myeloid neoplasm

Proliferation of myeloid cells originating from a primitive stem cell.


necrotizing scleritis

A severe form of scleritis with subtypes: necrotising zonal granulomatous inflammation, diffuse non-granulomatous chronic inflammation, mixed pattern of acute purulent inflammation mixed with granulomatous inflammation and sarcoidal pattern.


ocular pemphigoid

Ocular pemphigoid is a rare inflammatory eye disease characterized by sub-epithelial blistering manifesting with bilateral, asymmetrical, chronic or recurrent conjunctivitis and aberrant tissue regeneration leading to progressive conjunctival fibrosis, secondary corneal vascularization and, in some cases, blindness. Patients typically present with conjunctival redness, increased lacrimation, burning and/or foreign body sensation, edema, limbitis and/or varying degrees of ocular pain. Ankyloblepharon may be observed in end stages of the disease.


congenital disorder of glycosylation, type 2v


Bartter disease type 2

Any Bartter syndrome in which the cause of the disease is a mutation in the KCNJ1 gene.


acquired polycythemia

An instance of polycythemia that is acquired during the lifetime of the individual.


intellectual disability, autosomal recessive 25


brain-lung-thyroid syndrome

Brain-lung-thyroid syndrome is a rare disorder characterized by congenital hypothyroidism (CH), infant respiratory distress syndrome (IRDS) and benign hereditary chorea (BHC).


drug-induced akathisia

An uncomfortable feeling of inner restlessness and inability to stay still. It can be a side effect of psychotropic medications.


intrinsic asthma

An asthma that is triggered by factors not related to allergies such as anxiety, stress, exercise, cold air, dry air, hyperventilation, smoke, viruses, chemical irritants, autonomic imbalance, hormonal deficiencies and psychogenic influences. It is characterized by airway obstruction and inflammation that is at least partially reversible with medication. The symptoms include coughing, wheezing, shortness of breath or rapid breathing, and chest tightness.


eye adnexa disorder

A disease involving the ocular adnexa.


tick paralysis

Paralysis caused by a neurotropic toxin secreted by the salivary glands of ticks.


inborn disorder of pyridoxine metabolism

An inherited metabolic disease that is has its basis in the disruption of pyridoxine metabolic process.


dyskinesia with orofacial involvement, autosomal dominant

A rare paroxysmal movement disorder, with childhood or adolescent onset, characterized by paroxysmal choreiform, dystonic, and myoclonic movements involving the limbs (mostly distal upper limbs), neck and/or face, which can progressively increase in both frequency and severity until they become nearly constant. Patients may also present with delayed motor milestones, perioral and periorbital dyskinesias, dysarthria, hypotonia, and weakness.


ring chromosome 16

Ring chromosome 16 is characterized bypostnatal growthdeficiency, intellectual disability, microcephaly, broad flat nasal bridge, down-turned mouth, low-set and dysmorphic (abnormally-shaped) ears and speech delay.To date, less than 10 cases have been reported in the medical literature.


congenital disorder of glycosylation, type iit


developmental and epileptic encephalopathy, 14

Any early infantile epileptic encephalopathy in which the cause of the disease is a mutation in the KCNT1 gene.


Volkmann contracture

An ischemic contracture of the forearm that most often occurs secondary to trauma.


cortical dysplasia, complex, with other brain malformations 10


infectious discitis

An infection of the intervertebral disk space.


hyperphosphatasia with intellectual disability syndrome 1

Any hyperphosphatasia-intellectual disability syndrome in which the cause of the disease is a mutation in the PIGV gene.


autosomal dominant optic atrophy

An autosomal dominant hereditary condition characterized by optic atrophy and progressive visual loss.


bilateral retinoblastoma

Retinoblastoma involving both eyes. This occurs in the majority of patients with the inherited variant. A minority of patient with bilateral retinoblastoma were found to have involvement of the pineal gland as well.


frontal fibrosing alopecia

Frontal fibrosing alopecia (FFA) is a rare variant of lichen planopilaris characterized by symmetrical, progressive, band-like anterior hair loss of the scalp.


glossopharyngeal nerve disorder

A disease involving the glossopharyngeal nerve.


congenital absence of both forearm and hand, bilateral

Congenital absence of both forearm and hand, bilateral is a rare developmental defect during embryogenesis characterized by a bilateral, transverse absence of the radius and ulna (of varying terminal lengths), as well as all the elements composing the hand.


grade III meningioma

A malignant meningioma with aggressive clinical course. It recurs in approximately 50-78% of the cases. This category includes the anaplastic (malignant) meningioma, papillary meningioma, and rhabdoid meningioma.


Friedreich ataxia with retained reflexes


trisomy 17p

Trisomy 17p is a rare chromosomal abnormality resulting from the duplication of the short arm of chromosome 17 and characterized by pre- and post-natal growth retardation, developmental delay, hypotonia, digital abnormalities, congenital heart defects, and distinctive facial features.


patent ductus arteriosus 3

Any patent ductus arteriosus in which the cause of the disease is a mutation in the PRDM6 gene.


familial hemophagocytic lymphohistiocytosis 3

Any genetic hemophagocytic lymphohistiocytosis in which the cause of the disease is a mutation in the UNC13D gene.


Desulfovibrionaceae infectious disease

Infections with bacteria of the family Desulfovibrionaceae.


neuroaxonal dystrophy

A nonspecific term referring both to the pathologic finding of swelling of distal portions of axons in the brain and to disorders which feature this finding. Neuroaxonal dystrophy is seen in various genetic diseases, vitamin deficiencies, and aging. Infantile neuroaxonal dystrophy is an autosomal recessive disease characterized by arrested psychomotor development at 6 months to 2 years of age, ataxia, brain stem dysfunction, and quadriparesis. Juvenile and adult forms also occur. Pathologic findings include brain atrophy and widespread accumulation of axonal spheroids throughout the neuroaxis, peripheral nerves, and dental pulp. (From Davis & Robertson, Textbook of Neuropathology, 2nd ed, p927)


fibrocartilaginous embolism

Fibrocartilaginous embolism (FCE) is a rare type of embolism (sudden blocking of an artery) that occurs in the spinal cord. FCE occurs when materials that are usually found within the vertebral disk of the spine enter into the nearby vascular system (veins and arteries) and block one of the spinal cord vessels. The signs and symptoms of FCE often develop after a minor or even unnoticed btriggering eventb such as lifting, straining, or falling. Symptoms of FCE may include neck and/or back pain, progressive muscle weakness, and paralysis.The exact underlying cause of FCE is poorly understood. Most cases occur sporadically in people with no family history of the disease. Diagnosis is based on imaging of the spinal cord and ruling out other causes of a blockage of the vascular system within the spinal cord. Treatment is generally focused on preventing possible complications and improving quality of life with medications and physical therapy.


intellectual disability, autosomal dominant 6

Any autosomal dominant non-syndromic intellectual disability in which the cause of the disease is a mutation in the GRIN2B gene.


developmental and epileptic encephalopathy, 55


myoclonic dystonia 15

A myoclonic dystonia characterized by autosomal dominant inheritance that has material basis in variation in the chromosome region 18p11.


distal trisomy 17q

Distal trisomy 17q is a rare chromosomal anomaly syndrome with variable phenotype principally characterized by intellectual disability, developmental delay, short stature, craniofacial dysmorphism (incl. microcephaly, low posterior hairline, frontal bossing, bitemporal narrowing, low-set and malformed ears, flat nasal bridge, long philtrum, wide mouth with downturned corners, thin upper lip) and a short, webbed neck, as well as skeletal anomalies (e.g. brachyrhizomelia, poly-/syndactyly) and joint hyperlaxity. Cardiac, cerebral, and urogenital anomalies are also frequently associated.


congenital heart defects, multiple types


bladder lateral wall cancer

The aspect of the bladder wall that is located on the side.


congenital unguarded mitral orifice

Congenital unguarded mitral orifice is a rare, congenital, mitral valve malformation characterized by complete absence of mitral valve leaflets and tensor apparatus at the mitral annulus, which can present clinically with cyanosis, heart murmur, electrocardiogram abnormalities, mild cardiomegaly, or congestive heart failure. Association with heterotaxy, discordant atrioventricular connections, double-outlet right ventricle, pulmonary atresia or stenosis, thin left ventricular wall, and hypoplastic left heart syndrome has been reported.


cubital tunnel syndrome

Compression of the ULNAR NERVE in the cubital tunnel, which is formed by the two heads of the flexor carpi ulnaris muscle, humeral-ulnar aponeurosis, and medial ligaments of the elbow. This condition may follow trauma or occur in association with processes which produce nerve enlargement or narrowing of the canal. Manifestations include elbow pain and PARESTHESIA radiating distally, weakness of ulnar innervated intrinsic hand muscles, and loss of sensation over the hypothenar region, fifth finger, and ulnar aspect of the ring finger. (Joynt, Clinical Neurology, 1995, Ch51, p43)


anhidrotic ectodermal dysplasia-immunodeficiency-osteopetrosis-lymphedema syndrome

This syndrome is characterized by severe immunodeficiency, osteopetrosis, lymphedema and anhidrotic ectodermal dysplasia.


angioosteohypotrophic syndrome

Angioosteohypotrophic syndrome is a rare, congenital, vascular anomaly syndrome characterized by venous or, on occasion, arterial malformations which lead to soft tissue hypertrophy and bone hypoplasia. Affected limb is generally shortened, highly deformed, painful and edematous and associates bone and muscle hypotrophy. Single parts, or multiple small parts, of limbs are typically affected but more extensive involvement, including complete extremity, shoulder girdle and axilla, has been reported.


herpes zoster dermatitis

Painful, localized rash caused by reactivation of latent varicella zoster virus residing in nerve cell bodies, with resulting infection of the skin in the region supplied by the affected nerve.


trilateral retinoblastoma

Trilateral retinoblastoma refers to bilateral (or less often unilateral) retinoblastoma associated with an intracranial primitive neuroectodermal tumor in the pineal or suprasellar region. This syndrome is often associated with a increased familial incidence of retinoblastoma. (From Cancer 86(1): 135-141, 1999).


palpebral nevus

A melanocytic nevus that involves the skin of eyelid.


Congenital hypogonadotropic hypogonadism (CHH) is a rare disorder of sexual maturation characterized by gonadotropin (Gn) deficiency with low sex steroid levels associated with low levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH).


aortic valve disorder

A disease involving the aortic valve.


nosocomial infection

An infection acquired in a hospital or other healthcare setting.


uterine benign neoplasm

A non-metastasizing neoplasm that arises from the uterine corpus or the cervix. Representative examples include leiomyoma, adenomyoma, and endocervical polyp.


craniosynostosis syndrome, autosomal recessive

Autosomal recessive form of craniosynostosis.


epileptic encephalopathy, infantile or early childhood, 2


erythropoietic uroporphyria associated with myeloid malignancy


acute hemorrhagic encephalitis

Acute encephalitis that is characterized by bleeding.


autosomal dominant aplasia and myelodysplasia


epithelioid hemangioendothelioma

A low-grade malignant blood vessel neoplasm. It is characterized by the presence of epithelioid endothelial cells. The neoplastic cells are arranged in cords and nests, which are embedded in a myxoid to hyalinized stroma.


neurodevelopmental disorder with hearing loss and spasticity


retinitis pigmentosa 54

Any retinitis pigmentosa in which the cause of the disease is a mutation in the PCARE gene.


Chondrodysplasia - disorder of sex development is an extremely rare disorder of sex development, reported in only two siblings (one terminated in pregnancy) to date, characterized by the clinical features of 46,XY complete gonadal dysgenesis (normal external female genitalia, lack of pubertal development, primary amenorrhea, and hypergonadotrophic hypogonadism) in association with severe dwarfism with generalized chondrodysplasia (bell-shaped thorax, micromelia, brachydactyly). Other reported features in the live sibling included eye anomalies (hypoplastic irides, myopia, coloboma of optic disks), dysmorphic features (deep-set eyes, upslanting palpebral fissures, puffy eyelids, large ears and mouth, mild prognathism), muscular hypoplasia, mild intellectual deficiency and severe microcephaly with cerebellar vermis hypoplasia. An autosomal recessive inheritance has been suggested.


congenital supravalvular mitral ring

Congenital supravalvular mitral ring is a rare, congenital, mitral valve malformation characterized by an abnormal ridge of the connective tissue on the atrial side of the mitral valve, which can present clinically with signs and symptoms of left ventricle inflow obstruction (dyspnea, tachypnea, pulmonary hypertension, right ventricle hypertrophy, pulmonary edema). Association with other mitral valve anomalies, aortic stenosis, ventricular septal defect, patent ductus arteriosus, double-outlet right ventricle, pulmonary hypertension, and Shone complex has been reported.


McLeod neuroacanthocytosis syndrome

A form of neuroacanthocytosis and is characterized clinically by a Huntington's disease-like phenotype with an involuntary hyperkinetic movement disorder, psychiatric manifestations and cognitive alterations, and biochemically by absence of the Kx antigen and by weak expression of the Kell antigens.


NDE1-related microhydranencephaly

NDE1-related microhydranencephaly is a rare, hereditary syndrome with a central nervous system malformation as major feature characterized by extreme microcephaly and growth restriction, severe motor delay and mental retardation, and typical radiological findings of gross dilation of the ventricles resulting from the absence (or severe delay in the development) of cerebral hemispheres, hypoplasia of the corpus callosum, cerebellum, and brainstem. Associated features are thin bones and scalp rugae.


autosomal recessive nonsyndromic hearing loss 3

Any autosomal recessive nonsyndromic deafness in which the cause of the disease is a mutation in the MYO15A gene.


peroxisome biogenesis disorder 10A (Zellweger)


corneal dystrophy, lattice type 3A

Lattice corneal dystrophy type 3A is rare condition that affects the cornea. It is characterized primarily by protein clumps in the clear, outer covering of the eye which cloud the cornea and impair vision. Affected people also experience recurrent corneal erosion (separation of certain layers of the cornea), which is associated with severe pain and sensitivity to bright light. Lattice corneal dystrophy type 3A is caused by changes (mutations) in the TGFBI gene and is inherited in an autosomal dominant manner. The condition is usually treated surgically.


basal ganglia calcification, idiopathic, 4


calvarial doughnut lesions with bone fragility and spondylometaphyseal dysplasia


mucolipidosis type III, alpha/beta

Mucolipidosis III alpha/beta (MLIII alpha/beta) is a lysosomal disorder characterized by progressive slowing of the growth rate from early childhood, stiffness and pain in joints, gradual coarsening of facial features, moderate developmental delay and mild intellectual disability in most patients.


patterned macular dystrophy 1

Any patterned macular dystrophy in which the cause of the disease is a mutation in the PRPH2 gene.


placental villitis

Inflammatory process that involves the chorionic villi (villitis) of the placenta.


benign mastocytoma

A localized mast cell neoplasm without metastatic potential.


Developmental malformations-deafness-dystonia syndrome is characterized by the association of midline malformations, sensory hearing loss, and a delayed-onset generalized dystonia syndrome.


X-linked spinocerebellar ataxia type 3

A form of spinocerebellar degeneration characterized by onset in infancy of hypotonia, ataxia, sensorineural deafness, developmental delay, esotropia, and optic atrophy, and by a progressive course leading to death in childhood. It has been described one family with at least six affected males from five different sibships (connected through carrier females). It is transmitted as an X-linked recessive trait.


frontotemporal dementia and/or amyotrophic lateral sclerosis 7

Any amyotrophic lateral sclerosis in which the cause of the disease is a mutation in the CHMP2B gene.


cranioectodermal dysplasia 1

Any cranioectodermal dysplasia in which the cause of the disease is a mutation in the IFT122 gene.


PRKAR1B-related neurodegenerative dementia with intermediate filaments


bilineal acute myeloid leukemia

An acute leukemia of ambiguous lineage in which there is a dual population of blasts with each population expressing markers of a distinct lineage (myeloid and lymphoid or B-and T-lymphocyte). (WHO, 2001) -- 2003


polydactyly of a triphalangeal thumb, bilateral


amyotrophic lateral sclerosis type 20

Any amyotrophic lateral sclerosis in which the cause of the disease is a mutation in the HNRNPA1 gene.


aquarium granuloma

A skin condition caused by Mycobacterium marinum, characterized by a skin lesion that presents roughly three weeks after exposure.


aromatase deficiency

Aromatase deficiency disrupts the synthesis of estradiol, resulting in hirsutism of mothers during gestation of an affected child; pseudohermaphroditism and virilization in women; and tall stature, osteoporosis and obesity in men.


macrothrombocytopenia, isolated, 1, autosomal dominant

Any autosomal dominant macrothrombocytopenia in which the cause of the disease is a mutation in the TUBB1 gene.


alcoholic ketoacidosis

An acute disease characterized by severe ketoacidosis in the absence of diabetes mellitus and occuring in individuals with a history of prolonged excessive alcohol consumption. Disease manifestations include nausea, intractable vomiting, and abdominal pain. When treated, AKA resolves rapidly and completely with no apparent sequelae.


progressive encephalomyelitis with rigidity and myoclonus


immunotactoid or fibrillary glomerulopathy

A group of very rare glomerular diseases, composed of immunotactoid glomerulopathy (ITG) and non-amyloid fibrillary glomerulopathy (non-amyloid FGP), that are characterized by mesangial deposition of monoclonal microtubular or polyclonal fibrillar deposits. Both present clinically with nephrotic range proteinuria, hematuria and renal insufficiency leading to renal failure in many cases. ITG is more likely to manifest with underlying lymphoproliferative disease, hypocomplementemia, dysproteinemia, monoclonal gammopathy or occult cryoglobulinemia. Non-amyloid FGP is 10 times more frequent than ITG.


viral infection of central nervous system


pulmonary hypertension, primary, 4

Any primary pulmonary hypertension in which the cause of the disease is a mutation in the KCNK3 gene.


collagen type III glomerulopathy

A rare glomerular disease characterized by abnormal accumulation of type III collagen within the mesangium and subendothelial space of the glomerulus. Clinically it usually manifests with proteinuria (often in the nephrotic range), microscopic hematuria, peripheral edema and/or hypertension. In some cases progression to end-stage renal failure is observed.


contractures-ectodermal dysplasia-cleft lip/palate syndrome

Contractures - ectodermal dysplasia - cleft lip/palate is an ectodermal dyplasia syndrome characterized by severe arthrogryposis, multiple ectodermal dysplasia features, cleft lip/palate, facial dysmorphism, growth deficiency and a moderate delay of psychomotor development. Ectodermal dysplasia manifestations include sparse, brittle and hypopigmented hair, xerosis, multiple nevi, small conical shaped teeth and hypodontia, and facial dysmorphism with blepharophimosis, deep-set eyes and micrognathia.


neurodevelopmental disorder with motor regression, progressive spastic paraplegia, and oromotor dysfunction


microphthalmia, isolated, with coloboma 5

Any microphthalmia, isolated, with coloboma in which the cause of the disease is a mutation in the SHH gene.


spinocerebellar ataxia type 6

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.


mast syndrome

Autosomal recessive spastic paraplegia type 21 is a complex type of hereditary spastic paraplegia characterized by an onset in adolescence or adulthood of slowly progressive spastic paraparesis associated with the additional manifestations of apraxia, cognitive and speech decline (leading to dementia and akinetic mutism in some cases), personality disturbances and extrapyramidal (e.g. oromandibular dyskinesia, rigidity) and cerebellar (i.e. dysdiadochokinesia and incoordination) signs. Subtle abnormalities (e.g. developmental delays) may be noted earlier in childhood. A thin corpus callosum and white matter abnormalities are equally reported on magnetic resonance imaging.


unilateral multicystic dysplastic kidney

Unilateral multicystic dysplastic kidney is the form of multicystic dysplastic kidney (MCDK), a congenital anomaly of the kidney and urinary tract (CAKUT), in which one kidney is large, distended by multiple cysts, and non-functional.


developmental and epileptic encephalopathy, 84


gonococcal salpingitis

An salpingitis caused by infection with Neisseria gonorrhoeae.


subcorneal pustular dermatosis

A rare, benign, chronic disease characterized by sterile pustular eruption, typically involving the flexural sites of the trunk and proximal extremities.


acquired torsion dystonia

An instance of torsion dystonia that is acquired during the lifetime of the individual.


partial monosomy of the long arm of chromosome 9


fibrosis of extraocular muscles, congenital, 3b


childhood disintegrative disorder

A rare pervasive developmental disorder with a disease onset before the age of three and characterized by a dramatic loss of behavioral and developmental functioning after atleast two years of normal development. Manifestations of the disease include loss of speech, incontinence, communication and social interaction problems, stereotypical autistic behaviors and dementia.


46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency

Decreased activity of the steroidogenic enzyme, 17-beta-hydroxysteroid dehydrogenase, associated with mutation(s) in the HSD17B3 gene, leading to reduced testosterone production.


infantile-onset X-linked spinal muscular atrophy

A rare form of spinal muscular atrophy characterized by the neonatal onset of severe hypotonia, areflexia, profound weakness, multiple congenital contractures, facial dysmorphic features (myopathic face with open, tent-shaped mouth), cryptorchidism, and mild skeletal abnormalities (i.e. kyphosis, scoliosis), that is often preceded by polyhydramnios and reduced fetal movements in utero and followed by bone fractures shortly after birth. SMAX2 patients often have a limited life span, often succumbing to the disease within 2 years, as muscle weakness is progressive and chest muscle involvement eventually leads to ventilatory insufficiency and respiratory failure.


prostate stromal sarcoma

A rare malignant neoplasm arising from specialized prostatic stroma. It is characterized by the presence of stromal overgrowth and hypercellularity, increased number of mitotic figures, and pleomorphism.


amyotrophic lateral sclerosis type 10

Any amyotrophic lateral sclerosis in which the cause of the disease is a mutation in the TARDBP gene.


intellectual disability, autosomal recessive 46

Any autosomal recessive non-syndromic intellectual disability in which the cause of the disease is a mutation in the NDST1 gene.


myofibrillar myopathy 8

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


neuropathy, hereditary sensory and autonomic, type 2B

Any hereditary sensory and autonomic neuropathy type 2 in which the cause of the disease is a mutation in the RETREG1 gene.


complement component 9 deficiency

Any classic complement early component deficiency in which the cause of the disease is a mutation in the C9 gene.


congenital alveolar dysplasia due to FGF10

Any congenital alveolar dysplasia in which the cause of the disease is a mutation in the FGF10 gene.


macular amyloidosis

Macular amyloidosis (MA) is a rare chronic form of cutaneous amyloidosis, a skin disease characterized by the accumulation of amyloid deposits in the dermis, clinically characterized by pruritic hyperkeratotic gray-brown macules that give a rippled or reticulated pattern of pigmentation usually in the upper back and extensor sites of arms, forearms and legs, and histologically by the deposition of amyloid in the upper dermis and close to the basal cell layer of the epidermis. MA is commonly associated with other skin diseases, such as atopic dermatitis.


adolescent/adult onset autosomal dominant epilepsy with auditory features

A genetic focal epilepsy, with focal sensory auditory seizures seen in family members. Seizures often comprise such mild symptoms that they are undiagnosed. There are no implications expected for development or learning and seizures are typically infrequent and well controlled.


idiopathic linear interstitial keratitis

Idiopathic linear interstitial keratitis is a rare, acquired ocular disease characterized by migratory or non-migratory, horizontal, linear, stromal infiltrates that may heal spontaneously. Minimal vascularization and scarring may be observed but vision loss is not associated.


arthrogryposis-ectodermal dysplasia-other anomalies syndrome


dysostosis, Stanescu type

Stanescu type dysostosis is a rare form of osteosclerosis.


spastic ataxia 4

Any autosomal recessive spastic ataxia in which the cause of the disease is a mutation in the MTPAP gene.


fibroosseous pseudotumor of the digits

A non-neoplastic soft tissue disorder characterized by the localized formation of reactive fibrous and bone tissues. It usually occurs in the subcutaneous tissue of the proximal phalanx. Less frequently, it involves the toe. It presents with swelling and pain of the affected area. The prognosis is excellent. However, incomplete excision may lead to the re-growth of the lesion.


drug-resistant tuberculosis

Tuberculosis disease caused by Mycobacterium tuberculosis isolate that is resistant to one or more of the antitubercular medications.


vascular ectasia

Dilatation of the blood vessels.


autosomal recessive distal spinal muscular atrophy 2

Distal hereditary motor neuropathy, Jerash type is a rare, genetic neuromuscular disease characterized by progressive, symmetrical, moderate to severe, distal muscle weakness and atrophy, without sensory involvement, first affecting the lower limbs (towards the end of the first decade) and then involving (within two years) the upper extremities. Patients typically develop foot drop, pes varus, hammer toes and claw hands. Pyramidal tract signs (e.g. brisk knee reflexes, positive Babinski sign, absent ankle reflexes) are initially associated but regress as disease stabilizes (~10 years after onset).


developmental and epileptic encephalopathy 6B


digitotalar dysmorphism

Digitotalar dysmorphism, also known as distal arthrogryposis type 1 (DA1), is an autosomal dominant congenital anomaly characterized by contractures of the distal regions of the hands and feet with no facial involvement or any additional anomalies. It is the most common type of distal arthrogryposis.


congenital mitral valve insufficiency and/or stenosis


ocular cicatricial pemphigoid

Ocular cicatricial pemphigoid (OCP) is a form of mucous membrane pemphigoid (a group of rare, chronic autoimmune disorders) that affects the eyes. In the early stages, people with OCPgenerally experience chronic or relapsing conjunctivitis that is often characterized by tearing, irritation, burning, and/or mucus drainage. If left untreated, OCP can progress to severe conjunctiva scarring and vision loss. Involvement of other mucosal sites and the skin may also occur in OCP. The exact underlying cause is currently unknown. The treatment of OCP aims to slow disease progression and prevent complications. This usually involves long-term use of medications called immunomodulators which help regulate or normalize the immune system.


intellectual disability, autosomal dominant 20

Any autosomal dominant non-syndromic intellectual disability in which the cause of the disease is a mutation in the MEF2C gene.


cataract 29

A cataract that has material basis in variation in the region 2pter-p24.


junctional epidermolysis bullosa with pyloric atresia

Junctional epidermolysis bullosa with pyloric atresia is a severe subtype of junctional epidermolysis bullosa (JEB) characterized by generalized blistering at birth and congenital atresia of the pylorus and rarely of other portions of the gastrointestinal tract.


hypoplastic left heart syndrome 1

Any hypoplastic left heart syndrome in which the cause of the disease is a mutation in the GJA1 gene.


steroid-responsive encephalopathy associated with autoimmune thyroiditis


MASA syndrome

MASA syndrome (Mental retardation, Aphasia, Spastic paraplegia, Adducted thumbs) is a historical term used to describe a phenotype now considered to be part of the X-linked L1 clinical spectrum (L1 syndrome). MASA is characterized by mild to moderate intellectual deficit, delayed development of speech, hypotonia progressing to spasticity or spastic paraplegia, adducted thumbs, and mild to moderate distension of the cerebral ventricles.


nasolacrimal duct cyst

Nasolacrimal duct cyst describes a unilateral or bilateral congenital cyst of the nasolacrimal duct, which is almost always associated with dacryocystocele, presenting most commonly at birth or a few weeks of age (but rarely presenting in adulthood) as a benign, grayish blue mass in the inferomedial canthus or in the nasal cavity, that can cause epiphora, dacryocystitis (inflammation of the lacrimal sac) and nasal obstruction. It is more commonly reported in females.


complex neurodevelopmental disorder with motor features

A complex neurodevelopmental disorder that involves more than one phenotype associated with the central nervous system, including but not limited to intellectual disability, autism, and seizures (epilepsy). Additionally, the disorder features at least one phenotype associated with motor function, including but not limited to spasticity, hypo- or hypertonia, dyskinesia, choreo-athetosis, or ataxia.


B-lymphoblastic leukemia/lymphoma with hyperdiploidy

A precursor lymphoid neoplasm composed of B-lymphoblasts which contain more than 50 and usually less than 66 chromosomes. It has a favorable clinical outcome.


neonatal intrahepatic cholestasis due to citrin deficiency

Neonatal intrahepatic cholestasis due to citrin deficiency is a mild subtype of citrin deficiency characterized clinically by low birth weight, failure to thrive, transient intrahepatic cholestasis, multiple aminoacidemia, galactosemia, hypoproteinemia, hepatomegaly, decreased coagulation factors, hemolytic anemia, variable but mostly mild liver dysfunction, and hypoglycemia.


familial or sporadic hemiplegic migraine

Hemiplegic migraine (HM) is a rare variety of migraine with aura characterized by the presence of a motor weakness during the aura. Hemiplegic migraine has two main forms depending on the familial history: patients with at least one first- or second-degree relative who has aura including motor weakness have familial hemiplegic migraine (FHM); patients without such familial history have sporadic hemiplegic migraine (SHM).


Haim-Munk syndrome

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


congenital bile acid synthesis defect 6

Any congenital bile acid synthesis defect in which the cause of the disease is a mutation in the ACOX2 gene.


atypical dopamine transporter deficiency syndrome

A subset of SLC6A3-related DTDS cases which have later onset which ranges from late childhood to adulthood. This disorder is characterized by the presentation of parkinsonism-dystonia, rigidity, tremor, and bradykinesia after normal childhood development.


acute myeloid leukemia, t(10;11)(p12;q23)

Any acute myeloid leukemia that has the chromosomal anomaly t(10;11)(p12;q23). (A cytogenetic abnormality that refers to the translocation of chromosome 10p12 with chromosome 11q23. It is associated with acute myeloid leukemia in childhood.)


severe combined immunodeficiency due to CORO1A deficiency


odontochondrodysplasia 1

A very rare syndrome associating chondrodysplasia with dentinogenesis imperfecta.


frontotemporal dementia and/or amyotrophic lateral sclerosis 2

An amyotrophic lateral sclerosis that has material basis in mutation in the CHCHD10 gene on chromosome 22. It is characterized by adult onset of either frontotemporal dementia and/or amyotrophic lateral sclerosis.


suprabasal epidermolysis bullosa simplex

A form of epidermolysis bullosa simplex in which blistering occurs above the basal keratinocytes.


Bickerstaff brainstem encephalitis

Bickerstaff's brainstem encephalitis (BBE) is a rare post-infectious neurological disease characterized by the association of external ophthalmoplegia, ataxia, lower limb arreflexia, extensor plantar response and disturbance of consciousness (drowsiness, stupor or coma).


hypogonadotropic hypogonadism 27 without anosmia


overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes

A disease caused by mosaic gain-of-function (GoF) of several genes in the MTOR pathway (MTOR, PIK3CA, PIK3R2 and AKT3) are functionally the same despite significant phenotypic variability. These GoF variants result in overgrowth due to an over-activation of key genes in this pathway. The phenotypic variability is generally attributed to the mosaic fraction and affected tissue types. For example, macrocephaly is noted if the variant is identified in the brain, but non symmetric overgrowth of that limb is noted when the variant is only present in the affected limb. The pathologies of the affected tissue often reveal similar characteristics such as cellular overgrowth. However, this is not always the case especially with focal cortical dysplasia. At times the characteristics pathologies are not present in the tissue but sampling biases are an issue. FCD resections often involve a very small area and so a very small amount of tissue is available for pathology and it is not guaranteed that lesional tissue is sent. Therefore, having a single disease term which can encompass the phenotypic variability yet provide a unifying molecular diagnosis name makes sense given the common functional mechanism.


salpingitis isthmica nodosa

Formation of nodules in the isthmus of the fallopian tube due to fallopian tube diverticulosis. It may cause infertility or ectopic pregnancy.


developmental and epileptic encephalopathy 111


juvenile cataract-microcornea-renal glucosuria syndrome

Juvenile cataract - microcornea - renal glucosuria is an extremely rare autosomal dominant association reported in a single Swiss family and characterized clinically by juvenile cataract associated with bilateral microcornea, and renal glucosuria without other renal tubular defects.


autosomal recessive spinocerebellar ataxia 16

Any autosomal recessive cerebellar ataxia in which the cause of the disease is a mutation in the STUB1 gene.


incessant infant ventricular tachycardia

Incessant infant ventricular tachycardia is a rare type of ventricular tachycardia (VT) characterized by the presence of tachycardia originating from the ventricles, observed for more than 10% of a 24 hour monitoring period. Patients are either asymptomatic or present congestive heart failure.


thymic dysplasia

The developmental arrest and architectural distortion of the thymus that results in immunodeficiency.


congenital dyserythropoietic anemia type 4

Congenital dyserythropoietic anemia type IV (CDA IV) is a newly discovered form of CDA characterized by ineffective erythropoiesis and hemolysis that leads to severe anemia at birth.


Eales disease

Eales disease (ED) is an idiopathic, inflammatory retinal venous occlusive disease characterized by 3 stages: vasculitis, occlusion and retinal neovascularization, leading to recurrent vitreous hemorrhages and vision loss.


atopic keratoconjunctivitis

Atopic keratoconjunctivitis is a rare and chronic allergic disease of the cornea and conjunctiva occurring in all age groups characterized by severe itching and burning sensation, conjunctival injection, photophobia and edema with serious cases leading to ulceration of the cornea which can result in blindness. It is often associated with atopic dermatitis.


proximal myopathy with extrapyramidal signs

Proximal myopathy with extrapyramidal signs is a rare, hereditary non-dystrophic myopathy characterized by proximal muscle weakness, delayed motor development, learning difficulties, and progressive extrapyramidal motor signs including chorea, dystonia and tremor. Variable additional features have been reported - ataxia, microcephaly, ophthalmoplegia, ptosis, and optic atrophy.


familial syringomyelia

An instance of syringomyelia that is caused by an inherited modification of the individual's genome.


symphalangism, proximal, 1B

Any proximal symphalangism in which the cause of the disease is a mutation in the GDF5 gene.


partial duplication of the long arm of chromosome 12

Chromosome 12q duplication is a chromosome abnormality that occurs when there is an extra copy of genetic material on the long arm (q) of chromosome 12. The severity of the condition and the signs and symptoms depend on the size and location of the duplication and which genes are involved. Features that often occur in people with chromosome 12q duplication include developmental delay, intellectual disability, behavioral problems, growth delay, and distinctive facial features. Most cases are not inherited, but people can pass the duplication on to their children. Treatment is based on the signs and symptoms present in each person.


congenital achiasma

Congenital achiasma is a rare, genetic, non-syndromic cranial nerve and nuclear aplasia malformation characterized by the congenital absence of the optic chiasm, resulting from the failure of the optic nerve fibers to cross over and decussate to the contralateral hemisphere, leading to decreased vision, strabismus and congenital nystagmus in infancy.


anti-neutrophil antibody associated vasculitis

Group of systemic vasculitis with a strong association with ANCA. The disorders are characterized by necrotizing inflammation of small and medium size vessels, with little or no immune-complex deposits in vessel walls.


ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant


hereditary motor and sensory neuropathy, Okinawa type

Hereditary motor and sensory neuropathy, Okinawa type is a rare, genetic, axonal hereditary motor and sensory neuropathy characterized by the adult-onset of slowly progressive, symmetric, proximal dominant muscle weakness and atrophy, painful muscle cramps, fasciculations and distal sensory impairment, mostly (but not exclusively) in individuals (and their descendents) from the Okinawa region in Japan. Absent deep tendon reflexes, elevated creatine kinase levels and autosomal dominant inheritance are also characteristic.


infantile hypotonia-oculomotor anomalies-hyperkinetic movements-developmental delay syndrome


Mendelian neurodevelopmental disorder

A neurodevelopmental disorder that is caused by genetic modifications where those modifications are inherited from a parent's genome.


lymphoblastic leukemia, acute, with lymphomatous features


fibrothecoma

A sex cord-stromal tumor characterized by mixed features of both fibroma and thecoma.


trichofolliculoma

Trichofolliculoma is a rare benign follicular hamartoma that develops primarily on the face of adults, with a particular predilection for the back of the nose, but also on the neck or scalp. It presents as a solitary hemispheric flesh-colored nodule with a central pore or black dot that may contain a tuft of hair.


frontotemporal dementia and/or amyotrophic lateral sclerosis 3

An amyotrophic lateral sclerosis that has material basis in mutation in the SQSTM1 gene on chromosome 5q35.


congenital vitamin K-dependent coagulation factors deficiency

Congenital vitamin K-dependent coagulation factors deficiency involving multiple coagulation factors.


hemolytic anemia with thermal sensitivity of red cells


Enthesitis-related juvenile idiopathic arthritis is a subtype of juvenile idiopathic arthritis that is characterized by both arthritis and inflammation of an enthesitis site (the point at which a ligament, tendon, or joint capsule attaches to the bone). Signs and symptoms generally develop in late childhood or early adolescence and include pain, tenderness, and swelling in joints and at the enthesis. The knee and the back of the ankle (at the Achilles tendon) are the most commonly affected parts of the body. The underlying cause of enthesitis-related juvenile idiopathic arthritis is currently unknown (idiopathic). It is very rare for more than one member of a family to have juvenile arthritis; however, research suggests that having a family member with juvenile arthritis or any autoimmune disease may increase the risk of having juvenile arthritis, in general. Treatment usually involves different types of medications to help manage symptoms and/or physical therapy.


progressive rubella panencephalitis

A neurological disorder arising from primary rubella infection of the brain, characterized by chronic encephalitis. It is believed to be due to a persistence or reactivation of rubella virus infection. It usually manifesting between 8–19 years of age.


glycine N-methyltransferase deficiency

Glycine N-methyltransferase deficiency (GNMT deficiency) is a very rare condition characterized by persistent and isolated excess levels of methionine in the blood (hypermethioninemia). The only clinical abnormalities are mild increase of the liver size (hepatomegaly) and chronic elevation of the transaminase levels in the blood without liver disease. Methionine may also be increased in urine. However, because elevated levels of methionine in the blood itself is a risk factor for development of neurological signs and symptoms, people with GNMT deficiency can have neurological problems when methionine levelsare greater than 800μmol/L. GNMT deficiency is caused by mutations in the GNMT gene. Inheritance is autosomal recessive. Treatment is not needed in most cases.


pituitary hormone deficiency, combined, 6

Any combined pituitary hormone deficiencies, genetic form in which the cause of the disease is a mutation in the OTX2 gene.


cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 3

Any dysequilibrium syndrome in which the cause of the disease is a mutation in the CA8 gene.


renal dysplasia, unilateral

Unilateral renal dysplasia is a form of renal dysplasia (RD), a renal tract malformation in which the development of one kidney is abnormal and incomplete. Unilateral RD can be segmental, and of variable severity, with renal aplasia corresponding to extreme RD.


alcohol-induced disorders

Disorders stemming from the misuse and abuse of alcohol.


adult choroid plexus neoplasm

A choroid plexus neoplasm that occurs in an adult.


Charcot-Marie-Tooth disease type 1D

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.


type II mixed cryoglobulinemia

Type II mixed cryoglobulinemia, a relatively rare clinico-serological subtype of mixed cryoglobulinemia (MC), is an immune complex disorder characterized by purpura, weakness and arthralgia and defined immunochemically by cryoglobulins composed of polyclonal IgGs (autoantigens) and monoclonal IgM (autoantibody).


Dianzani autoimmune lymphoproliferative disease (DALD) is a very rare disorder characterized by autoimmunity, lymphadenopathy and/or splenomegaly.


syndromic X-linked intellectual disability 14

Any X-linked syndromic intellectual disability in which the cause of the disease is a mutation in the UPF3B gene.


hereditary sensory and autonomic neuropathy type 1

Hereditary sensory neuropathy type I (HSN I) is a slowly progressive neurological disorder characterized by prominent predominantly distal sensory loss, autonomic disturbances, autosomal dominant inheritance, and juvenile or adulthood disease onset.


partial duplication of the short arm of chromosome 17


12q14 microdeletion syndrome

12q14 microdeletion syndrome is characterized by mild intellectual deficit, failure to thrive, short stature and osteopoikilosis. It has been described in four unrelated patients. The syndrome appears to be caused by a heterozygous deletion at chromosome region 12q14, which was detected in three of the four patients. The deleted region contains the LEMD3 gene: mutations in this gene have already been implicated in osteopoikilosis.


agammaglobulinemia 10, autosomal dominant

An agammaglobulinemia characterized by early-childhood onset of recurrent viral and bacterial infections affecting various organ systems, particularly the sinopulmonary system. Laboratory studies show low or absent circulating B cells and hypo- or agammaglobulinemia. Affected individuals may have adverse reactions to certain vaccinations, such as the polio vaccine. Treatment with replacement Ig is effective; hematopoietic stem cell transplantation has also been reported.


microsporidiosis

A fungal infection caused by Microsporidia. It occurs in immunocompromised patients, causing diarrhea and wasting.


mitochondrial complex 1 deficiency, nuclear type 22


developmental and epileptic encephalopathy, 7

KCNQ2-related epileptic encephalopathy is a severe form of neonatal epilepsy that usually manifests in newborns during the first week of life with seizures (that affect alternatively both sides of the body), often accompanied by clonic jerking or more complex motor behavior, as well as signs of encephalopathy such as diffuse hypotonia, limb spasticity, lack of visual fixation and tracking and mild to moderate intellectual deficiency. The severity can range from controlled to intractable seizures and mild/moderate to severe intellectual disability.


collagen 6-related myopathy

A qualitative or quantitative defect of collagen 6 disorder that covers a wide spectrum of musculoskeletal phenotypes caused by dominant and recessive mutations in the three major collagen VI genes: COL6A1, COL6A2, and COL6A3. These variants lead to a variety of overlapping phenotypes, ranging from severe congenital muscle weakness, hypotonia, torticollis and contractures with loss or non-development of ambulation on one end and childhood to adult onset mild muscle weakness, stiffness, and joint hyperlaxity on the other.


uterine corpus mixed epithelial and mesenchymal neoplasm

A primary, benign or malignant neoplasm of the uterine corpus characterized by the presence of an epithelial and a mesenchymal component. Representative examples include adenomyoma, adenosarcoma, and carcinosarcoma.


acute rheumatic heart disease

Pancarditis, involving inflammation of the endocardium, myocardium, and epicardium. It results from an autoimmune reaction following an infection with Streptococcus pyogenes (Group A Streptococci).


nemaline myopathy 5B, autosomal recessive, childhood-onset


pyruvate kinase deficiency of red cells

Hemolytic anemia due to red cell pyruvate kinase (PK) deficiency is a metabolic disorder characterized by a variable degree of chronic nonspherocytic hemolytic anemia.


adult intestinal botulism

A very rare form of botulism, a rare acquired neuromuscular junction disease with descending flaccid paralysis caused by botulinum neurotoxins (BoNTs), and is due to intestinal colonization by Clostridium botulinum leading to toxin-mediated infection with toxemia.


amyotrophic lateral sclerosis 27, juvenile


AGAT deficiency

L-Arginine:glycine amidinotransferase (AGAT) deficiency is a very rare type of creatine deficiency sydrome characterized by global developmental delay, intellectual disability, and myopathy.


tremor, hereditary essential, 5

Any essential tremor in which the cause of the disease is a mutation in the TENM4 gene.


Curry-Jones syndrome

Curry-Jones syndrome is a form of syndromic craniosynostosis, characterized by unilateral coronal craniosynostosis or multiple suture synostosis associated with complete or partial agenesis of the corpus callosum, preaxial polysyndactyly and syndactyly of hands and/or feet, along with anomalies of the skin (characteristic pearly white areas that become scarred and atrophic, abnormal hair growth around the eyes and/or cheeks, and on the limbs), eyes (iris colobomas, microphthalmia,) and intestine (congenital short gut, malrotation, dysmotility, chronic constipation, bleeding and myofibromas). Developmental delay and variable degrees of intellectual disability may also be observed. Multiple intra-abdominal smooth muscle hamartomas, trichoblastoma of the skin, occipital meningoceles and development of desmoplastic medulloblastoma have been reported.


uremic neuropathy

Neuropathy resulting from uremia.


Balo concentric sclerosis

Tumefactive multiple sclerosis is characterized by a tumor-like lesion larger than two centimeters and signs and symptoms similar to those of a brain tumor. It is a rare form of multiple sclerosis (MS). Symptoms of tumefactive MS often differ from other MS cases and may include, headaches, changes in thinking, confusion, speech problems, seizures, and weakness. The cause of tumefactive MS is not known. It often develops into the relapsing-remitting form of MS. In other cases there is only one occurrence of the condition. In still others the disease process remains less clear. While there is no cure for tumefactive MS, treatments such as corticosteroids are available to decrease disease activity.


X-linked intellectual disability-plagiocephaly syndrome is characterized by severe intellectual deficit, brachycephaly, plagiocephaly, prominent forehead and coarse facial features. It has been described in two males from one family. Two females belonging to the same family displayed moderate intellectual deficit but no craniofacial dysmorphism.


Seckel syndrome 9

Any Seckel syndrome in which the cause of the disease is a mutation in the TRAIP gene.


ocular albinism with late-onset sensorineural deafness

Ocular albinism with late-onset sensorineural deafness (OASD), is a rare, X-linked inherited type of ocular albinism described in one African kindred (7 males over 3 generations) to date, characterized by severe visual impairment, translucent pale-blue iridies, a reduction in the retinal pigment and moderately severe deafness by middle age (fourth to fifth decade of life). It is unclear whether it is allelic to X-linked recessive ocular albinism or a contiguous gene syndrome.


sporadic idiopathic steroid-resistant nephrotic syndrome with focal segmental hyalinosis


Neu-Laxova syndrome 1

Any Neu-Laxova syndrome in which the cause of the disease is a mutation in the PHGDH gene.


undifferentiated round cell sarcoma

An undifferentiated soft tissue sarcoma characterized by the presence of uniform round or ovoid malignant cells with a high nuclear to cytoplasmic ratio.


linear skin defects with multiple congenital anomalies 1

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


polyvalvular heart disease syndrome

Polyvalvular heart disease syndrome is a recently described syndrome characterized by the combination of polyvalvular heart disease, short stature, facial anomalies and intellectual deficit.


congenital stationary night blindness 2A

Any congenital stationary night blindness in which the cause of the disease is a mutation in the CACNA1F gene.


polyneuropathy in collagen vascular disease


oocyte/zygote/embryo maturation arrest 20


age related macular degeneration 7

Any age-related macular degeneration in which the cause of the disease is a mutation in the HTRA1 gene.


hypomyelinating leukodystrophy 2

Any leukodystrophy in which the cause of the disease is a mutation in the GJC2 gene.


trisomy

A chromosomal abnormality consisting of the presence of one chromosome in addition to the normal diploid number.


smooth muscle cancer

A malignant neoplasm arising from smooth muscle.


hereditary thrombocytosis with transverse limb defect

Thrombocythemia with distal limb defects is a rare, genetic syndrome with limb reduction defects characterized by thrombocytosis, unilateral transverse limb defects (ranging from absence of phalanges to absence of hand or forearm) and splenomegaly.


chorea, remitting, with nystagmus and cataract


Prata-Liberal-Goncalves syndrome

Acrodysplasia scoliosis is a rare, genetic dysostosis disorder characterized by brachydactyly and other finger/toe anomalies (short and/or wide metacarpals, abnormal or absent metatarsals, broad halluces), carpal synostosis, fused cervical vertebrae, scoliosis and spina bifida occulta. There have been no further descriptions in the literature since 1984.


retinitis pigmentosa 14

Any retinitis pigmentosa in which the cause of the disease is a mutation in the TULP1 gene.


hereditary thermosensitive neuropathy

Hereditary thermosensitive neuropathy is a rare, demyelinating, hereditary motor and sensory neuropathy characterized by reversible episodes of ascending muscle weakness, paresthesias and areflexia triggered by a febrile episode, with or without pressure palsy.


Nonrhizomelic chondrodysplasia punctata is a form of chondrodysplasia punctata, a group of diseases in which the common characteristic is bone calcifications near joints from birth. Nonrhizomelic chondrodysplasia punctata is not an entity in itself but covers several diseases with variable clinical findings and modes of transmission.


benign neoplasm of cornea

A benign neoplasm that involves the cornea.


immunodeficiency 33

Any immunodeficiency disease in which the cause of the disease is a mutation in the IKBKG gene.


early onset absence epilepsy

A childhood electroclinical syndrome characterized by the occurrence of typical absence seizures starting between the age of four and ten years.


primary non-gestational choriocarcinoma of ovary

Primary non-gestational choriocarcinoma of ovary is a rare ovarian germ cell malignant tumor, arising from primordial germ cells, usually presenting with nausea, vomiting, abdominal pain, menstrual irregularities, and characterized by fast growth pattern, metastasis to lung, liver and brain and production of human chorionic gonadotrophin (hCG). It is apparently chemoresistant and has a worse prognosis than gestational choriocarcinoma and hence should be distinguished from the latter by DNA polymorphism.


Megalocornea-intellectual disability syndrome is a rare intellectual disability syndrome most commonly characterized by megalocornea, congenital hypotonia, varying degrees of intellectual disability, psychomotor/developmental delay, seizures, and mild facial dysmorphism (including round face, frontal bossing, antimongoloid slant of the eyes, epicanthal folds, large low set ears, broad nasal base, anteverted nostrils, and long upper lip). Interfamilial and intrafamilial clinical variability has been reported.


hereditary hypophosphatemic rickets with hypercalciuria

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a hereditary renal phosphate-wasting disorder characterized by hypophosphatemia and hypercalciuria associated with rickets and/or osteomalacia.


holoprosencephaly 8

A holoprosencephaly that has material basis in variation in the chromosome region 14q13.


hyperlipoproteinemia type 3

Hyperlipoproteinemia (HLP) type 3 is a rare combined hyperlipidemia characterized by high levels of cholesterol and triglycerides, transported by intermediate density lipoproteins (IDLs), and a high risk of premature atherosclerosis and cardiovascular disease.


Aphalangy-hemivertebrae-urogenital-intestinal dysgenesis is an extremely rare congenital limb malformation syndrome, described in only 3 patients to date, and characterized by the association of hypoplasia or aplasia of the hand and foot phalanges, hemivertebrae and various urogenital and/or intestinal abnormalities (i.e. dysgenesis of the urogenital tract and rectum). There have been no further descriptions in the literature since 1991.


theca steroid-producing cell malignant tumor of ovary, not further specified

Malignant steroid cell tumor of the ovary, not otherwise specified is a rare malignant sex cord stromal tumor of ovary of unknown histological lineage, occurring in adult women, characterized, in most cases, by manifestations of androgen excess (hirsutism, hair loss, amenorrhea, or oligomenorrhea) and, occasionally, Cushing syndrome.


primary ciliary dyskinesia 28

Any primary ciliary dyskinesia in which the cause of the disease is a mutation in the SPAG1 gene.


epilepsy, familial adult myoclonic, 2

Any epilepsy, familial adult myoclonic in which the cause of the disease is a mutation in the ADRA2B gene.


congenital hematological disorder

A disorder of the blood that is present at birth.


prolactin producing pituitary tumor

An adenoma or carcinoma of the anterior lobe of the pituitary gland that produces prolactin.


transient bullous dermolysis of the newborn

Transient bullous dermolysis of the newborn is a rare subtype of dystrophic epidermolysis bullosa (DEB) characterized by generalized blistering at birth that usually regresses within the first 6 to 24 months of life.


congenital hydrocephalus

Hydrocephalus that is present at birth.


corneal dystrophy, Fuchs endothelial, 8

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


chronic canaliculitis

Chronic form of actinomycosis.


type 2 collagenopathy

Any disease or disorder in which the cause of the disease is a mutation in the COL2A1 gene.


bullous systemic lupus erythematosus

A manifestation of systemic lupus erythematosus with a widespread vesiculobullous eruption.


diabetic encephalopathy

A brain disease that is characterized by functional impairment of cognition, cerebral signal conduction, neurotransmission and synaptic plasticity, and underlying structural pathology associated with diabetes.


isolated ankyloblepharon filiforme adnatum

Isolated ankyloblepharon filiforme adnatum (AFA) is characterized by the presence of single or multiple thin bands of connective tissue between the upper and lower eyelids, preventing full opening of the eye. Several cases have been reported. It can occur sporadically or following an autosomal dominant transmission pattern. In some cases, AFA can be associated with other disorders, such as trisomy 18. The bands should be removed to avoid amblyopia and this can easily be performed in the neonatal period by cutting with tissue scissors.


isolated microphthalmia 4

Any isolated microphthalmia in which the cause of the disease is a mutation in the GDF6 gene.


Oguchi disease

Oguchi disease is an autosomal recessive retinal disorder characterized by congenital stationary night blindness and the Mizuo-Nakamura phenomenon.


cone-rod dystrophy 20

Any cone-rod dystrophy in which the cause of the disease is a mutation in the POC1B gene.


spermatogenic failure 10

Any azoospermia in which the cause of the disease is a mutation in the SEPT12 gene.


B4GALT1-congenital disorder of glycosylation

B4GALT1-CDG is a congenital disorder of glycosylation characterized by macrocephaly due to Dandy-Walker malformation, hydrocephaly, hypotonia, myopathy and coagulation anomalies. To date, only one case has been reported. The syndrome is associated with mutations in the GALT1 gene (localized to region q13 of chromosome 9) leading to a deficiency in the Golgi apparatus enzyme beta-1,4-galactosyl transferase.


thanatophoric dysplasia type 2

Thanatophoric dysplasia characterized by a cloverleaf-like skull and straight femurs.


mucolipidosis type IV

A lysosomal storage disease characterized clinically by psychomotor retardation and visual abnormalities including corneal clouding, retinal degeneration, or strabismus.


mitochondrial complex 1 deficiency, nuclear type 3


ectodermal dysplasia 7, hair/nail type

Any pure hair and nail ectodermal dysplasia in which the cause of the disease is a mutation in the KRT74 gene.


Lemierre syndrome

Lemierre syndrome is a rare, potentially lethal, oropharyngeal infectious disease occurring in immunocompetent adolescents and young adults that is mainly due to Fusobacterium necrophorum and that is characterized by septic thrombophlebitis of the internal jugular vein that leads to septic, usually pulmonary, embolism, associated with ENT (ear, nose, and throat) infection that manifests with fever, neck pain, and tonsillopharyngitis.


cervical disk degenerative disorder

Any degenerative disorder affecting one or more vertebral disks of the cervical spine.


sarcoglycanopathy

Deficiencies or mutations in the genes for the sarcoglycan complex subunits. A variety of phenotypes are associated with these mutations including a subgroup of autosomal recessive limb girdle muscular dystrophies, cardiomyopathies, and respiratory deficiency.


2-hydroxyglutaric aciduria

2-Hydroxyglutaric aciduria is a group of neurometabolic disorders with a wide clinical spectrum ranging from severe neonatal presentations to progressive forms, and asymptomatic cases, characterized biochemically by increased levels of 2-hydroxyglutaric acid in the plasma, cerebrospinal fluid and urine.


sella turcica neoplasm

A benign or malignant neoplasm that occurs in sella turcica. Representative examples include craniopharyngioma and pituitary gland adenoma.


testicular dysgenesis syndrome

A syndrome comprising testicular germ cell cancer, cryptorchidism and some cases of hypospadias and male infertility with impaired development of the testis.


neonatal encephalopathy with non-epileptic myoclonus

A disorder characterized onset at birth of profound encephalopathy with hypotonia, Respiratory insufficiency central hypoventilation, a persistent suppression burst pattern of EEG background, and recurrent bouts of myoclonus that are not accompanied by epileptic discharges on electroencephalography. Evolution to pharmacoresistant seizures is common and continued profound global developmental delay.


autosomal recessive nonsyndromic congenital nuclear cataract


mitochondrial dna depletion syndrome 16B (neuroophthalmic type)


partial septate uterus

Partial septate uterus is a rare, non-syndromic uterovaginal malformation characterized by a uterus that has a longitudinal septum which extends from the uterine fundus and does not reach the internal cervical os (variable lengths and widths may be observed). Although frequently asymptomatic, an increased risk of poor reproductive outcome has been observed. Urinary tract abnormalities are very rarely associated.


Duane-radial ray syndrome

A syndrome of multiple congenital anomalies and is characterized by ocular manifestations (uni- or bilateral Duane anomaly (95% of cases), congenital optic nerve hypoplasia or optic disk coloboma), bilateral deafness and radial ray malformation that can include thenar hypoplasia and/or hypoplasia or aplasia of the thumbs; hypoplasia or aplasia of the radii; shortening and radial deviation of the forearms; triphalangeal thumbs; and duplication of the thumb (preaxial polydactyly).The phenotype overlaps with other SALL4>/i> related disorders including acro-renal-ocular syndrome and Holt-Oram syndrome (see these terms). Transmission is autosomal dominant.


bullous pyoderma gangrenosum

A rare subtype of pyoderma gangrenosum disease characterized by grouped vesicles that rapidly spread and coalesce to form large bullae, which evolve into ulcerations that have an erythematous peripheral halo and central necrosis, mainly affecting the upper limbs and face. Lymphoproliferative diseases are frequently associated, thus prognosis is often compromised.


posteroinferior myocardial infarction

An electrocardiographic finding of an injury in leads corresponding to the anatomic region of the posteroinferior wall of the heart.


atypical childhood epilepsy with centrotemporal spikes

A childhood-onset epilepsy that is characterized by frequent seizures of multiple types, including nocturnal focal motor and fronto-parietal opercular seizures, and daytime focal motor seizures with negative myoclonus and atypical absence seizures. Centrotemporal sharp waves are seen on EEG. During the phase of the epilepsy when seizures are frequent, neuropsychological deficits and motor impairment may be present. These deficits improve when seizures remit.


Ciliophora infectious disease

Infections with protozoa of the phylum ciliophora.


short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans

A rare genetic skeletal disorder characterized clinically by abnormal chondro-skeletal development, disproportionate short stature and skeletal deformation mainly affecting the knees, hips, ankles and elbows with onset generally in late childhood or adolescence.


ring dermoid of cornea

Ring dermoid of cornea is characterized by annular limbal dermoids (growths with a skin-like structure) with corneal and conjunctival extension. Less than 30 cases have been described. Transmission is autosomal dominant and mutations in the PITX2 gene have been suggested as a potential cause of the condition.


congenital heart defects, multiple types, 5


mitochondrial DNA depletion syndrome 12B (cardiomyopathic type), autosomal recessive

An inherited condition caused by mutation(s) in the SLC25A4 gene, encoding ADP/ATP translocase 1. It is characterized by hypertrophic cardiomyopathy.


episodic ataxia type 6

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.


legionellosis

Any disease caused by Legionella bacteria.


mitochondrial complex 1 deficiency, nuclear type 5