severe Canavan disease

Severe Canavan disease (CD) is a rapidly progressing neurodegenerative disorder characterized by leukodystrophy with macrocephaly, severe developmental delay and hypotonia.


premature ovarian failure 2B

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

Any primary ovarian failure in which the cause of the disease is a mutation in the POF1B gene.


neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal recessive


qualitative or quantitative defects of filamin C


hereditary sclerosing poikiloderma with tendon and pulmonary involvement

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


neuronopathy, distal hereditary motor, type 2A

Any neuronopathy, distal hereditary motor in which the cause of the disease is a mutation in the HSPB8 gene.


spondylometaphyseal dysplasia, pagnamenta type


systemic mastocytosis

Systemic mastocytosis (SM) comprises a heterogeneous group of rare acquired and chronic hematological malignancies that are related to an abnormal proliferation of mast cells in tissue, including bone marrow, with or without skin involvement.


partial duplication of the short arm of chromosome 1


Charcot-Marie-Tooth disease type 4B3

Charcot-Marie-Tooth disease type 4B3 (CMT4B3) is a subtype of Charcot-Marie-Tooth type 4 characterized by a childhood onset of slowly progressing, demyelinating sensorimotor neuropathy, focally folded myelin sheaths in nerve biopsy, reduced nerve conduction velocities (less than 38 m/s), and the typical CMT phenotype (i.e. distal muscle weakness and atrophy, and sensory loss).


conventional lipoma

A benign well-circumscribed tumor, composed of lobules of mature adipocytes, that arises within subcutaneous tissue, deep soft tissues or on the surface of bones.


Karsch-Neugebauer syndrome

Karsch-Neugebauer syndrome is a rare syndrome characterized by split-hand and split-foot deformity and ocular abnormalities, mainly a congenital nystagmus.


congenital factor V deficiency

Congenital factor V deficiency is an inherited bleeding disorder due to reduced plasma levels of factor V (FV) and characterized by mild to severe bleeding symptoms.


intellectual disability, autosomal recessive 1

Any autosomal recessive non-syndromic intellectual disability in which the cause of the disease is a mutation in the PRSS12 gene.


polyposis, intestinal, scattered and discrete


cone-rod dystrophy 19

Any cone-rod dystrophy in which the cause of the disease is a mutation in the TTLL5 gene.


autosomal dominant nonsyndromic hearing loss 47

An autosomal dominant nonsyndromic deafness that has material basis in variation in the chromosome region 9p22-p21.


drug-induced localized lipodystrophy

Drug-induced localized lipodystrophy is a rare, acquired, localized lipodystrophy characterized by the appearance of asymptomatic, well-demarcated, variably sized, depressed, lipoatrophic lesions secondary to subcutaneous, intradermic or intramuscular drug injection, including corticosteroids, insulin, human growth hormone and antibiotics. Skin coloration may vary from white or hypopigmented to reddish, pinkish or violaceous. Epidermal atrophy may be also present.


hereditary spastic paraplegia 49

Any hereditary spastic paraplegia in which the cause of the disease is a mutation in the TECPR2 gene.


pterin-4 alpha-carbinolamine dehydratase 1 deficiency

Pterin-4 alpha-carbinolamine dehydratase 1 (PCBD1) deficiency is considered a transient and benign form of hyperphenylalaninemia due to tetrahydrobiopterin deficiency, characterized by muscular hypotonia, irritability (detected by EEG), slow acquisition of psychomotor skills, age-dependent movement disorders, including dystonia and an accompanying excretion of 7-substituted pterins. Neurological developement is normal with dietary control of blood phenyalanine. PCBD1 is inherited in an autosomal recessive manner.


bilateral parasagittal parieto-occipital polymicrogyria


acrocephalopolydactyly

Acrocephalopolydactyly, also known as Elejalde syndrome, is an extremely rare lethal autosomal recessive disorder characterized by massive birth weight, swollen globular body, generalized edema, short limbs, postaxial polydactyly, thick skin, facial dysmorphism (slanted palpebral fissures, hypertelorism, epicanthic folds, dysplastic ears), excessive connective tissue, renal dysplasia, and in some patients, organomegaly, craniosynostosis with acrocephaly, omphalocele, cleft palate, and cryptorchidism. Fewer than 10 cases have been reported to date.


blastoma

A malignant neoplasm composed of undifferentiated cells.


acute myeloid leukemia, KRAS gene mutation

Any acute myeloid leukemia that has the chromosomal anomaly KRAS gene mutation. (A change in the nucleotide sequence of the KRAS gene.)


sclerosing liposarcoma

A morphologic variant of well differentiated liposarcoma occurring most often in the retroperitoneum and paratesticular area. It is characterized by the presence of bizarre hyperchromatic stromal cells and rare multivacuolated lipoblasts within a fibrous stroma.


malignant Sertoli-Leydig cell tumor of ovary

Malignant Sertoli-Leydig cell tumor of ovary is a rare malignant sex cord stromal tumor of ovary occuring typically in young women and characterized by manifestations of androgen excess (hirsutism, hair loss, amenorrhea, or oligomenorrhea), when functional.


late-onset retinal degeneration

Late-onset retinal degeneration is an inherited retinal dystrophy characterized by delayed dark adaptation and nyctalopia and drusen deposits presenting in adulthood, followed by cone and rod degeneration that presents in the sixth decade of life, which leads to central vision loss. Anterior segment features such as peripupillary iris transillumination defects and abnormally long anterior zonular insertions are also observed. Choroidal neovascularization and glaucoma may occur in the late stages of the disease.


metaphyseal acroscyphodysplasia

Metaphyseal acroscyphodysplasia is an extremely rare form of metaphyseal dysplasia characterized by the distinctive radiological sign of cone-shaped upper tibial and lower femoral epiphyses embedded in large cup-shaped metaphyses, associated with short stature and micromelia. Upper limb involvement includes brachydactyly and phalangeal and metacarpal cone-shaped epiphyses. The association of metaphyseal acroscyphodysplasia with psychomotor delay and alopecia has also been reported in some cases.


granulomatous hypophysitis

Granulomatous hypophysitis is rare pathology that mimics pituitary adenoma.


X-linked colobomatous microphthalmia-microcephaly-intellectual disability-short stature syndrome is a rare syndromic microphthalmia disorder characterized by microphthalmia with coloboma (which may involve the iris, cilary body, choroid, retina and/or optic nerve), microcephaly, short stature and intellectual disability. Other eye abnormalities such as pendular nystagmus, esotropia and ptosis may also be present. Additional associated abnormalities include kyphoscoliosis, anteverted pinnae with minimal convolutions, diastema of the incisors and congenital pes varus.


blepharophimosis-ptosis-epicanthus inversus syndrome type 1


bladder trigone cancer

A malignant neoplasm involving the trigone of urinary bladder.


aortic arch defects

Congenital abnormalities of the aortic arch result from aberrant development of one or more components of the embyronic pharangeal arch system. Any component of tihs system can regress or persist abnormally, resulting in an extensive array of aortic arch anomalies. Clinically, they are classified by those that cause (or are likely to cause) physiolgogical abnormalities and those that do not. Physiologic abnormalities include tracheobronchial compression, esophageeal compression, and abnormal blood flow patteren.


partial deletion of the long arm of chromosome 8

Chromosome 8q deletion is a chromosome abnormality that occurs when there is a missing copy of the genetic material located on the long arm (q) of chromosome 8. The severity of the condition and the signs and symptoms depend on the size and location of the deletion and which genes are involved. Features that often occur in people with chromosome 8q deletion include developmental delay, intellectual disability, behavioral problems, and distinctive facial features. Most cases are not inherited, but people can pass the deletion on to their children. Treatment is based on the signs and symptoms present in each person.


visual epilepsy

Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or 'seizure disorder.'


sclerosteosis

Sclerosteosis is a very rare serious sclerosing hyperostosis syndrome characterized clinically by variable syndactyly and progressive skeletal overgrowth (particularly of the skull), resulting in distinctive facial features (mandibular overgrowth, frontal bossing, midfacial hypoplasia), cranial nerve entrapment causing facial palsy and deafness, and potentially lethal elevation of intracranial pressure.


congenital pulmonary venous return anomaly

Congenital pulmonary venous return anomaly is a cardiac malformation where some or all of the pulmonary veins drain into the right atrium or the systemic veins, with or without the presence of pulmonary venous obstruction, leading to various manifestations such as fatigue, exertional dyspnea, pulmonary arterial hypertension, cyanosis and progressive congestive heart failure. The two main subtypes are congenital partial pulmonary venous return anomaly (PAPVC), where one or a few of the pulmonary veins are anomalous, and congenital total pulmonary venous return anomaly (TAPVC), where all of the pulmonary veins are anomalous.


craniosynostosis, Philadelphia type

Craniosynostosis, Philadelphia type is a form of syndromic craniosynostosis, characterized by sagittal/dolichocephalic head shape with a relatively normal facial appearance and complete soft tissue syndactyly of hand and foot. Transmission is autosomal dominant with variable expression of the hand findings, and incomplete penetrance of the sagittal craniosynostosis. Craniosynostosis, Philadelphia type has been suggested to share the same etiology as syndactyly type 1A.


infantile-onset autosomal recessive nonprogressive cerebellar ataxia


exogenous ochronosis

Exogenous ochronosis refers tothe bluish-black discoloration of certain tissues, such as the ear cartilage, the ocular (eye) tissue, and other body locations when it is due toexposure to various substances.It has been reported most commonly with topical application of hydroquinones to the skin. The discolorationmay becaused byan effect ontyrosinase(an enzyme located in melanocytes, which are skincells that produce pigment), or by inhibiting homogentisic acid oxidase, resulting in the accumulation and deposition of homogentisic acid (HGA) in cartilage. The discoloration is often permanent, but when exogenous ochronosis is caused by topical hydroquinones, carbon dioxide lasers and dermabrasion have been reported to be helpful. Exogenous ochronosis is different from hereditary ochronosis, which is an inherited condition that occurs with alkaptonuria.


autosomal recessive spastic paraplegia type 70

Autosomal recessive spastic paraplegia type 70 is a very rare, complex subtype of hereditary spastic paraplegia that presents in infancy with delayed motor development (i.e. crawling, walking) and is characterized by lower limb spasticity, increased deep tendon reflexes, extensor plantar responses, impaired vibratory sensation at ankles, amyotrophy and borderline intellectual disability. Additional signs may include gait disturbances, Achilles tendon contractures, scoliosis and cerebellar abnormalities.


hemochromatosis type 2

Hemochromatosis type 2 (juvenile) is the early-onset and most severe form of rare hereditary hemochromatosis (HH), a group of diseases characterized by excessive tissue iron deposition of genetic origin.


MAN2B2 deficiency

Any non-severe combined immunodeficiency in which the cause of the disease is variation in the MAN2B2 gene.


Char syndrome

Char syndrome is characterized by the triad of patent ductus arteriosus (PDA), facial dysmorphism and hand anomalies.


hereditary inclusion body myopathy type 4

Hereditary inclusion body myopathy type 4 is a rare non-dystrophic myopathy characterized by slowly progressive muscular weakness and atrophy initially involving proximal lower limbs and hip girdle and later on shoulder girdle, proximal upper limbs and axial muscles. Ambulation is usually preserved. Congophilic inclusions with cytoplasmic inclusions of 15-21 nm filaments on electron microscopy are revealed in muscle biopsy.


chronic apical periodontitis

Chronic form of periapical periodontitis.


rat-bite fever

An infectious disease that is caused transmitted by the bite of a rat. Two species of bacteria can cause the infection: Streptobacillus moniliformis and Spirillum minus.


adult liposarcoma

A malignant neoplasm arising from adipocytes, that occurs in adults. The tumor maybe one of several histologic types including well-differentiated, dedifferentiated, myxoid/round cell, and pleomorphic liposarcoma.


age related macular degeneration 14

An age related macular degeneration associated with variation at or near the C2 and CFB genes on chromosome 6p21.


contractures-developmental delay-Pierre Robin syndrome


familial polycythemia

Polycythemia that occurs in groups of related individuals.


distal 16p11.2 microdeletion syndrome

Distal 16p11.2 microdeletion syndrome is a rare chromosomal anomaly syndrome resulting from the partial deletion of the short arm of chromosome 16 with a highly variable phenotype typically characterized by developmental delay, mild intellectual disability and autism spectrum disorder. Macrocephaly (apparent by 2 years of age), structural brain malformations, epilepsy, vertebral anomalies and obesity are frequently associated.


intellectual developmental disorder, X-linked, syndromic, Pilorge type


spinocerebellar ataxia type 40

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


craniosynostosis-hydrocephalus-Arnold-Chiari malformation type I-radioulnar synostosis syndrome

Capra-DeMarco syndrome is characterized by sagittal craniosynostosis, hydrocephalus, Chiari I malformation and radioulnar synostosis. Other clinical findings include blepharophimosis, small low-set ears, hypoplastic philtrum, kidney malformation, and hypogenitalism.


subacute thyroiditis

Self-limited inflammation of the thyroid gland characterized by the presence of multinucleated giant cells. Patients present with neck pain, often associated with fever and dysphagia. The clinical course includes an initial phase of hyperthyroidism, followed by a phase of hypothyroidism, and eventually a return to normal thyroid function.


leukoplakia of gingiva

A clinical term that indicates the presence of a white patch on the surface of the gum which cannot be characterized as any other disease. It may be a precancerous condition and in most cases histologic examination reveals keratosis.


lower clivus meningioma

A meningioma that affects the lower clivus.


autosomal dominant nonsyndromic hearing loss 56

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


congenital myasthenic syndrome with tubular aggregates

A congenital myasthenic syndrome with a finding of tubular aggregates in myofibers.


anti-NMDA receptor encephalitis

An autoimmune acute encephalitis caused by antibodies against the glutamate NMDA receptor. It usually affects females and in the majority of cases it is associated with the presence of a tumor, most commonly an ovarian teratoma. The presence of a tumor in patients with this form of encephalitis implies that the latter is a paraneoplastic syndrome. It is manifested with psychiatric symptoms and epileptic seizures. It is a potentially lethal disorder; however, it is usually reversible with the prompt removal of the tumor.


achromatopsia 7

Any achromatopsia in which the cause of the disease is a mutation in the ATF6 gene.


hearing loss, autosomal recessive

Autosomal recessive form of nonsyndromic deafness.


autosomal recessive nonsyndromic hearing loss 30

Any autosomal recessive nonsyndromic deafness in which the cause of the disease is a mutation in the MYO3A gene.


hypoparathyroidism, familial isolated, 2


invasive non-typhoidal salmonellosis

Invasive non-typhoidal salmonellosis (iNTS) is a rare bacterial infectious disease caused by extraintestinal infection of non-typhoidal serotypes of Salmonella enterica in patients with underlying HIV infection, malaria or malignancy. It has a high mortality rate and patients typically present with fever, pallor and respiratory signs (cough, tachnypnea, pneumonia). Gastrointestinal manifestations (diarrhea, vomit, abdominal pain) are not common. Occasionally, organ absseses, septic shock and meningitis may be observed.


anti-neutrophil cytoplasmic 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.


Lowry-MacLean syndrome

Lowry-MacLean syndrome is a very rare syndrome characterized by microcephaly, craniosynostosis, glaucoma, growth failure and visceral malformations.


progressive myoclonic epilepsy type 3

Any progressive myoclonic epilepsy in which the cause of the disease is a mutation in the KCTD7 gene.


ciliary body cancer

A malignant neoplasm involving the ciliary body.


lip herpes simplex type 2 infectious disorder

Any herpes simplex type 2 infectious disease that involves the lip.


X-linked intellectual disability, Seemanova type is characterized by microcephaly, intellectual deficit, growth retardation and hypogenitalism. It has been described in four boys from one family. A characteristic facies and ophthalmologic anomalies were also present and included microphthalmia, microcornea and cataract. Transmission is X-linked.


toxic oil syndrome

Toxic oil syndrome is a rare intoxication, due to consumption of a rapeseed oil denatured with aniline 2%, characterized by generalized vascular lesions affecting all organs and vessels (including veins and arteries) and presenting with severe incapacitating myalgias, marked peripheral eosinophilia and pulmonary infiltrates.


nanophthalmos 2

Any nanophthalmia in which the cause of the disease is a mutation in the MFRP gene.


disseminated intravascular coagulation in newborn

A clotting condition characterized as a disruption in the homeostatic balance of the coagulation and fibrinolytic systems presenting as a pathological activation of coagulation mechanisms leading to the formation of small clots inside the blood vessels throughout the body of the newborn.


dysmorphism-short stature-deafness-disorder of sex development syndrome

Dysmorphism-short stature-deafness-disorder of sex development syndrome is characterized by dysmorphism (including facial asymmetry, arched eyebrows, hypertelorism, broad and flat nasal bridge, microtia, small nose with anteverted nostrils, micrognathia), deafness, cleft palate, male pseudohermaphroditism, and growth and psychomotor retardation. It has been described in two siblings. It is transmitted as an autosomal recessive trait.


isolated lissencephaly type 1 without known genetic defects

Isolated lissencephaly type 1 without known genetic defects belongs to the genetically heterogeneous group, classic lissencephaly. It is a diagnosis of exclusion, when neither associated malformations nor family history are present, and in the absence of mutations of genes known to be involved in classic lissencephaly. Clinically patients present with the common features of classic lissencephaly such as developmental delay, intellectual disability, and seizures.


mesenteric vascular occlusion

Obstruction of the flow in the splanchnic circulation by atherosclerosis; embolism; thrombosis; stenosis; trauma; and compression or intrinsic pressure from adjacent tumors. Rare causes are drugs, intestinal parasites, and vascular immunoinflammatory diseases such as periarteritis nodosa and thromboangiitis obliterans. (From Juergens et al., Peripheral Vascular Diseases, 5th ed, pp295-6)


mitochondrial complex 2 deficiency, nuclear type 4


mixed germ cell-sex cord-stromal tumor

A biphasic neoplasm that arises from the ovary or the testis. It is characterized by the presence of neoplastic germ cells and neoplastic sex cord-stromal cells. It includes the gonadoblastoma and mixed germ cell-sex cord stromal tumor, unclassifiable.


drug-induced dyskinesia

Abnormal movements, including hyperkinesis; hypokinesia; tremor; and dystonia, associated with the use of certain medications or drugs. Muscles of the face, trunk, neck, and extremities are most commonly affected. Tardive dyskinesia refers to abnormal hyperkinetic movements of the muscles of the face, tongue, and neck associated with the use of neuroleptic agents (see antipsychotic agents). (Adams et al., Principles of Neurology, 6th ed, p1199)


X-linked corneal dermoid

X-linked corneal dermoid (X-CND) is an exceedingly rare, benign, congenital, corneal tumor characterized by bilateral opacification of the cornea with superficial grayish layers and irregular raised whitish plaques, as well as fine blood vessels covering the central cornea, and intact peripheral corneal borders.No other ocular or systemic abnormality is noted. The pattern of inheritance described in the affected family is consistent with X-linked transmission.


MYH7-related skeletal myopathy

Laing distal myopathy, also called myopathy distal, type 1 (MPD1), is characterized by early-onset selective weakness of the great toe and ankle dorsiflexors, and a very slowly progressive course.


mitochondrial DNA depletion syndrome, myopathic form

Myopathic mitochondrial DNA (mtDNA) depletion syndrome is one of the main forms of mtDNA depletion syndrome that displays a broad phenotypic spectrum but that is most often characterized by hypotonia, proximal muscle weakness, facial and bulbar weakness and failure to thrive.


von Willebrand disease type 2A

Type 2A von Willebrand disease (type 2A VWD) is a subtype of type 2 VWD characterized by a bleeding disorder associated with a decrease in the affinity of the Willebrand factor (von Willebrand factor; VWF) for platelets and the subendothelium caused by a deficiency of high molecular weight VWF multimers.


skull disorder

A non-neoplastic or neoplastic disorder that affects structures of the skull.


acquired deficiency anemia

An instance of deficiency anemia that is acquired during the lifetime of the individual.


keratomalacia

An eye disorder that results from vitamin A deficiency, with basis in disruption of maintenance of the specialized epithelial surfaces, leading to atrophic changes in the normal mucosal surface, with loss of goblet cells, and replacement of the normal epithelium by an inappropriate keratinized stratified squamous epithelium. In addition, the substantia propria of the cornea breaks down and liquefies, resulting in keratomalacia.


nasal cavity neoplasm

A benign or malignant neoplasm that affects the nasal cavity. Representative examples of benign neoplasms include Schneiderian papilloma and salivary gland-type adenoma. Representative examples of malignant neoplasms include carcinoma and lymphoma.


glycogen storage disease IXa2

Any glycogen storage disease in which the cause of the disease is a mutation in the PHKA2 gene, with no PHK in liver, but normal activity in erythrocytes.


developmental and epileptic encephalopathy, 67


congenital nervous system disorder

An abnormality of the nervous system that is present at birth or detected in the neonatal period.


prelingual non-syndromic genetic hearing loss

A rare, genetically highly heterogeneous otorhinolaryngologic disease, resulting from inner and/or middle ear or hearing nerve anomalies, typically characterized by bilateral, severe to profound hearing loss (mean sensorineural hearing impairment of 60 dB or more for 500-, 1,000-, and 2,000-Hz frequency tones in the better ear) which occurs before the onset of speech development and is not associated with visible external ear abnormalities or any other medical problems. It is usually nonprogressive and impedes oral language acquisition.


pachyonychia congenita 3

Any pachyonychia congenita in which the cause of the disease is a mutation in the KRT6A gene.


erythrokeratodermia variabilis et progressiva 2


benign secondary hypertension

Mild to moderate high blood pressure that is caused by an underlying medical condition.


camptodactyly, myopia, and fibrosis of the medial rectus muscle of eye

A rare multiple congenital anomalies syndrome characterized by the association of camptodactyly, multiple eye defects (fibrosis of the medial rectus muscle, severe myopia, ptosis and exophthalmos), scoliosis, flexion contractures and facial anomalies (arched eyebrows, facial asymmetry with an abnormal skull shape, a prominent nose, small mouth, low-set and dysplastic ears, and a low nuchal hairline).


iatrogenic botulism

Iatrogenic botulism is the most recent man-made form of botulism, a rare acquired neuromuscular junction disease with descending flaccid paralysis caused by botulinum neurotoxins (BoNTs), and it may occur as an adverse event after therapeutic or cosmetic use.


fibrosis of extraocular muscles, congenital, 3A, with or without extraocular involvement

Any congenital fibrosis of extraocular muscles in which the cause of the disease is a mutation in the TUBB3 gene.


retinitis pigmentosa 19

Any retinitis pigmentosa in which the cause of the disease is a mutation in the ABCA4 gene.


autosomal dominant nonsyndromic hearing loss 2B

Any autosomal dominant nonsyndromic deafness in which the cause of the disease is a mutation in the GJB3 gene.


oculoglandular tularemia

A tularemia that results in inflammation of eye and swelling of lymph glands in front of the ear.


familial hypertryptophanemia

Familial hypertryptophanemia is characterized by intellectual deficit associated with behavioral problems: periodic mood swings, exaggerated affective responses and abnormal sexual behavior. Twelve cases have been reported so far. Congenital abnormalities in tryptophan metabolism appear to be responsible for the tryptophanemia and tryptophanuria.


obesity due to prohormone convertase I deficiency

Prohormone convertase-I deficiency is the rarest form of monogenic obesity. The disorder is characterized by severe childhood obesity, hypoadrenalism, reactive hypoglycaemia, and elevated circulating levels of certain prohormones.


pachyonychia congenita

Pachyonychia congenita (PC) is a rare genodermatosis predominantly featuring painful palmoplantar keratoderma, thickened nails, cysts and whitish oral mucosa.


Listeria meningitis

Inflammation of the meninges caused by listeria monocytogenes infection, usually occurring in individuals under the age of 3 years or over the age of 50 years. It may occur at any age in individuals with immunologic deficiency syndromes. Clinical manifestations include fever, altered mentation, headache, meningeal signs, focal neurologic signs, and seizures. (From Medicine 1998 Sep;77(5):313-36)


Hinman syndrome

Hinman syndrome (HS) or non-neurogenic neurogenic bladder is a voiding dysfunction of the bladder of neuropsychological origin that is characterized by functional bladder outlet obstruction in the absence of neurologic deficits.


benign neoplasm of hypopharynx

A benign neoplasm that involves the hypopharynx.


abducens nerve neoplasm

A neoplasm involving a abducens nerve.


hereditary amyloidosis

Hereditary amyloidosis refers to a group of inherited conditions that make up one of the subtypes of amyloidosis. Hereditary amyloidosisis characterized by the deposit of an abnormal protein called amyloid in multiple organs of the body where it should not be, which causes disruption of organ tissue structure and function. In hereditary amyloidosis, amyloid deposits most often occur in tissues of the heart, kidneys, and nervous system. While symptoms of hereditary amyloidosis may appear in childhood, most individuals do not experience symptoms until adulthood. There are many types of hereditary amyloidosis associated with different gene mutations and abnormal proteins. The most common type of hereditary amyloidosis is transthyretin amyloidosis (ATTR),a condition in which the amyloid deposits are most often made up of the transthyretin protein which is made in the liver. Other examplesof hereditary amyloidosis include, but are not limited to, apolipoprotein AI amyloidosis (A ApoAI), gelsolin amyloidosis (A Gel), lysozyme amyloidosis (A Lys), cystatin C amyloidosis (A Cys), fibrinogen Aα-chain amyloidosis (A Fib), and apolipoprotein AII amyloidosis (A ApoAII). Most types of hereditary amyloidosis are inherited in an autosomal dominant manner. Treatment is focused on addressing symptoms of organ damage and slowing down the production of amyloid when possible through methods such as liver transplants.


developmental and epileptic encephalopathy 102


thecoma

An ovarian or testicular stromal tumor characterized by the presence of lipid-rich neoplastic spindle cells. In females, uterine bleeding is the most common symptom. A minority of post-menopausal women with thecoma have an associated endometrial adenocarcinoma or rarely a malignant mixed mullerian tumor or endometrial stromal sarcoma. Rare cases with nuclear atypia and mitotic activity may metastasize. In males, thecomas are rare and they usually present as slow growing, sometimes painful masses. Metastases have not been reported.


riboflavin transporter deficiency

A progressive motor neuron disorder characterized by respiratory insufficiency, sensorineural deafness and progressive ponto-bulbar palsy.


acute myeloid leukemia by FAB classification

Acute myeloid leukemias that do not fulfill the criteria for inclusion in the group of acute myeloid leukemias which have recurrent genetic abnormalities or myelodysplastic changes, or are therapy-related. This category includes entities classified according to the French-American-British classification scheme.


Neu-Laxova syndrome 2

Any Neu-Laxova syndrome in which the cause of the disease is a mutation in the PSAT1 gene.


acute myeloid leukemia, del(5q31-q32)

Any acute myeloid leukemia that has the chromosomal anomaly del(5q31-q32). (A cytogenetic abnormality that refers to deletion of chromosome bands 31-32 on the long arm of chromosome 5.)


GJC2-related late-onset primary lymphedema

A rare genetic primary lymphedema characterized by lymphedema of all four limbs with age of onset ranging from birth to adulthood. Manifestations are of variable severity, and upper limb involvement may develop only later in the disease course. Recurrent episodes of cellulitis and skin infections are observed in severe cases. Varicose veins and venous incompetence have been reported in association.


proteostasis deficiencies

Disorders caused by imbalances in the protein homeostasis network - synthesis, folding, and transport of proteins; post-translational modifications; and degradation or clearance of misfolded proteins.


neoplasm of femur

A neoplasm (disease) that involves the femur.


blastema predominant kidney Wilms tumor

Wilms tumor of the kidney characterized by the predominance of the blastema component.


primary adrenal insufficiency

A hormonal disorder that occurs when the adrenal glands fail to release adequate amounts of glucocorticoids (cortisol), mineralocorticoids (aldosterone, 11-deoxycorticosterone), and androgens (dehydroepiandrosterone) to meet physiologic needs, despite release of ACTH from the pituitary.


factor V short isoforms-related bleeding disorder


simple endometrial hyperplasia

A proliferation of endometrial cells resulting in glandular enlargement and budding without changes in the basic structure of the endometrium. Epithelial atypia may be present or absent.


MELAS syndrome caused by mutation in MTND6

Any MELAS syndromein which the cause of the disease is a mutation in the MTND6 gene.


acute myeloid leukemia, inv(16)(p13.1;q22)

Any acute myeloid leukemia that has the chromosomal anomaly inv(16)(p13.1;q22). (A chromosomal inversion that involves chromosome 16. It is associated with the development of acute myeloid leukemia CBFB-MYH11, acute myelomonocytic leukemia with abnormal eosinophils, and granulocytic sarcoma.)


solitary fibrous tumor

Solitary fibrous tumor (SFT) represents a diverse group of ubiquitous rare spindle cell neoplasms that may be benign or malignant and that most frequently arises from the pleura and peritoneum and rarely from other sites such as head and neck, liver and skeletal muscle. SFT may be clinically asymptomatic or may present with enlarging mass, compressive effects depending on the site involved and rarely with paraneoplastic manifestations (osteoarthropathy or hypoglycemia).


neurodevelopmental disorder with seizures and brain atrophy


skin sarcoma

A sarcoma that arises from the skin. Representative examples include Kaposi sarcoma, angiosarcoma, lymphangiosarcoma, liposarcoma, and leiomyosarcoma.


mitochondrial myopathy-cerebellar ataxia-pigmentary retinopathy syndrome


ectodermal dysplasia-blindness syndrome

Ectodermal dysplasia-blindness syndrome is characterized by intellectual deficit, blindness caused by ocular malformations (microphthalmia, microcornea and sclerocornea), short stature, dysmorphic facial features (narrow nasal bridge and prominent ears), hypotrichosis, and malaligned teeth. It has been described in two siblings (brother and sister) and is likely to be transmitted as an autosomal recessive trait.


Lipodystrophy-intellectual disability-deafness syndrome is an extremely rare form of genetic lipodystrophy, reported in 3 patients from one family to date, characterized by generalized congenital lipodystrophy, low birth weight, progressive sensorineural deafness occurring in childhood, intellectual deficit, progressive osteopenia, delayed skeletal maturation, skeletal abnormalities described as slender, undermineralized tubular bones, and dense metaphyseal striations in the distal femur, ulna and radius of older patients. Autosomal recessive inheritance has been suggested.


beriberi

Beriberi is a condition that occurs in people who are deficient in thiamine (vitamin B1). There are two major types of beriberi: wet beriberi which affects the cardiovascular system and dry beriberi which affects the nervous system. People with wet beriberi may experience increased heart rate, shortness of breath, and swelling of the lower legs. Signs and symptoms of dry beriberi include difficulty walking; loss of feeling in the hands and/or feet; paralysis of the lower legs; mental confusion; speech difficulty; pain; and/or vomiting. Beriberi is rare in the United States since many foods are now vitamin enriched; however, alcohol abuse, dialysis and taking high doses of diuretics increases the risk of developing the condition. In most cases,beriberi occurs sporadically in people with no family history of the condition. A rare condition known as genetic beriberi is inherited (passed down through families) and is associated with an inability to absorb thiamine from foods. Treatment generally includes thiamine supplementation, given by injection or taken by mouth.


familial isolated congenital asplenia

Familial isolated congenital asplenia is a rare, non-syndromic, potentially life-threatening visceral malformation characterized by the absence of normal spleen function, resulting in a primary immunodeficiency. Typically, the condition manifests with severe, recurrent, overwhelming infections (especially pneumococcal sepsis) in otherwise apparently healthy infants. In adults with no history of severe sepsis in infancy, thrombocytosis may be the presenting sign. Howell-Jolly bodies on blood smears and an absent spleen on abdominal ultrasound examination are highly suggestive associated findings.


Leydig cell hypoplasia

A condition in males that affects sexual development. It is characterized by underdevelopment of the Leydig cells, which are cells in the testes that secrete male sex hormones (androgens) and are important for male sexual development. Individuals with LCH have a typical male genetic make-up (46, XY), but due to lowered levels of androgens, may have a range of genital (reproductive organ) differences. Individuals with LCH may have a small penis (micropenis),the opening of the urethra may be located on the underside of the penis (hypospadias), or the scrotum may be divided into two halves (bifid scrotum). Given these differences in development, the external genitalia may not appear clearly male or female (ambiguous genitalia). Some individuals with LCH can have female external genitalia and small testes that have not descended and are located in the pelvis, abdomen, or groin. This may be referred to as type 1, whereas less severe cases might be called type 2. LCH is inherited in an autosomal recessive manner and is caused by mutations in the LHCGR gene.Although there is no specific treatment or cure for LCH, there may be ways to manage the symptoms. A team of doctors or specialists is often needed to figure out the treatment options for each person.


epileptic encephalopathy, infantile or early childhood, 3


partial deletion of the short arm of chromosome 6


frontotemporal dementia and/or amyotrophic lateral sclerosis 8


congenital myasthenic syndrome 18

Any congenital myasthenic syndrome in which the cause of the disease is a mutation in the SNAP25 gene.


Charcot-Marie-Tooth disease type 2I

Autosomal dominant Charcot-Marie-Tooth disease type 2I (CMT2I) is a form of axonal Charcot-Marie-Tooth disease, a peripheral sensorimotor neuropathy, characterized by a late onset with severe sensory loss (paresthesia and hypoesthesia) associated with distal weakness, mainly of the legs, and absent or reduced deep tendon reflexes.


congenital disorder of glycosylation with defective fucosylation 2


epidermolysis bullosa simplex 1B, generalized intermediate

Non-Dowling-Meara generalized epidermolysis bullosa simplex, formerly known as epidermolysis bullosa simplex, Kobner type (EBS-K) is a generalized basal subtype of epidermolysis bullosa simplex (EBS) characterized by non-herpetiform blisters and erosions arising in particular at sites of friction.


retroperitoneal neoplasm

A benign or malignant neoplasm that affects the retroperitoneum.


X-linked intellectual disability

An X-linked intellectual deficiency in which not enough information is known, reported or published to indicate whether a gene causes non-syndromic or syndromic presentations.


atrial fibrillation, familial, 9

Any familial atrial fibrillation in which the cause of the disease is a mutation in the KCNJ2 gene.


facioscapulohumeral muscular dystrophy 3, digenic


autonomic dysreflexia

A syndrome associated with damage to the spinal cord above the mid thoracic level (see SPINAL CORD INJURIES) characterized by a marked increase in the sympathetic response to minor stimuli such as bladder or rectal distention. Manifestations include HYPERTENSION; TACHYCARDIA (or reflex bradycardia); FEVER; FLUSHING; and HYPERHIDROSIS. Extreme hypertension may be associated with a STROKE. (From Adams et al., Principles of Neurology, 6th ed, pp538 and 1232; J Spinal Cord Med 1997;20(3):355-60)


chondroblastic osteosarcoma

An osteosarcoma characterized by the presence of atypical cartilage of variable cellularity. It may or may not be associated with the presence of myxoid areas or focal bone formation.


juvenile neuronal ceroid lipofuscinosis

A genetically heterogeneous group of neuronal ceroid lipofuscinoses (NCLs) typically characterized by onset at early school age with vision loss due to retinopathy, seizures and the decline of mental and motor capacities.


EPHB4-related lymphatic-related hydrops fetalis

A rare primary lymphedema characterized by a highly variable lymphatic phenotype ranging from severe lymphatic-related hydrops fetalis, which may cause perinatal demise or fully resolve to become completely asymptomatic, to a mild presentation in older patients with persistent varicose veins, peripheral edema, and impaired lymph drainage in the lower limbs. Atrial septal defect has been described in association and may be the only anomaly in some patients.


benign connective and soft tissue neoplasm

A non-metastasizing neoplasm that arises from the connective and soft tissue. Representative examples include lipoma, leiomyoma, fibroma, and osteoma.


primary unilateral adrenal hyperplasia

Primary unilateral adrenal hyperplasia (PUAH) is a surgically-correctable form of primary (hyper) aldosteronism (PA) characterized by renin suppression, unilateral aldosterone hypersecretion, and moderate to severe hypertension secondary to hyperplasia of the adrenal gland.


mixed phenotype acute leukemia with MLL rearranged

An acute biphenotypic leukemia that is characterized by blasts which carry a translocation between the MLL (KMT2A) gene at 11q23.3 and another gene partner.


autosomal recessive ataxia, Beauce type

A rare disorder characterized by a slowly progressive pure cerebellar ataxia associated with dysarthria. It has been described in 53 individuals from 26 families of Canadian origin. The mode of transmission is autosomal recessive. Positional cloning has led to the identification of several gene mutations.


classic paraneoplastic limbic encephalitis

Classic paraneoplastic limbic encephalitis is a rare neuroimmunological disorder characterized by the sudden onset of seizures, progressive memory impairment (which may develop into dementia) and psychiatric manifestations (e.g. depression, personality changes, loss of social inhibition) associated with cancer (most commonly small-cell carcinoma of the lung) in the absence of tumor cell invasion of the nervous system. Other reported features include ataxia, dystonia, paresthesia, tremors, paranoid ideation, and hallucinations. The presence of antibodies that act on neuronal antigens (such as anti-Hu, anti-Ma2, anti-amphiphysin) are typically observed.


autosomal recessive cerebellar ataxia

Autosomal recessive cerebellar ataxias (ARCA) are a heterogeneous group of rare neurological disorders involving both the central and peripheral nervous system (and in some cases other systems and organs), and characterized by degeneration or abnormal development of the cerebellum and spinal cord and, in most cases, early onset occurring before the age of 20 years.


intellectual developmental disorder, autosomal recessive 73


nephronophthisis 20

Any nephronophthisis in which the cause of the disease is a mutation in the MAPKBP1 gene.


viral pericarditis

Pericarditis that is caused by an infection with a viral agent.


Friedreich ataxia

An inherited condition that affects the nervous system and causes movement problems. People with this condition develop impaired muscle coordination (ataxia) that worsens over time. Other features include the gradual loss of strength and sensation in the arms and legs, muscle stiffness (spasticity), and impaired speech. Many individuals have a form of heart disease called hypertrophic cardiomyopathy. Some develop diabetes, impaired vision, hearing loss, or an abnormal curvature of the spine (scoliosis). Most people with Friedreich ataxia begin to experience the signs and symptoms around puberty.


severe combined immunodeficiency due to IKK2 deficiency

Severe combined immunodeficiency due to IKK2 deficiency is a rare, genetic form of primary immunodeficiency characterized by life-threatening bacterial, fungal and viral infections with the onset in infancy, and failure to thrive. Typically, hypogammaglobulinemia or agammaglobulinemia and normal levels of T and B cells are present.


polyradiculoneuropathy

Diseases characterized by injury or dysfunction involving multiple peripheral nerves and nerve roots. The process may primarily affect myelin or nerve axons. Two of the more common demyelinating forms are acute inflammatory polyradiculopathy (guillain-barre syndrome) and polyradiculoneuropathy, chronic inflammatory demyelinating. Polyradiculoneuritis refers to inflammation of multiple peripheral nerves and spinal nerve roots.


developmental and epileptic encephalopathy, 1

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


Minamata disease

A neurological syndrome caused by severe mercury poisoning.


X-linked cerebral adrenoleukodystrophy

A peroxisomal disease characterized by severe inflammatory demyelination in the brain, and often associated with adrenal insufficiency.


endocervicitis

Inflammation of the endocervix.


hemorrhagic disease due to alpha-1-antitrypsin Pittsburgh mutation


median cleft lip/mandibule

Midline cleft of lower lip is a rare anomaly defined as Cleft No. 30 in Tessier's classification.


intracranial liposarcoma

A malignant adipose tissue neoplasm of the intracranial region.


partial duplication of the short arm of chromosome 19


twin reversal arterial perfusion syndrome


thrombophilia due to protein S deficiency, autosomal recessive


occupational dermatitis

Contact dermatitis associated with allergens or irritants found in the workplace.


telangiectasia, hereditary hemorrhagic, type 2

Any hereditary hemorrhagic telangiectasia in which the cause of the disease is a mutation in the ACVRL1 gene.


distal hereditary motor neuropathy type 7

Distal hereditary motor neuropathy type 7 is a rare, slowly progressive genetic peripheral neuropathy characterized by distal atrophy and weakness affecting the upper limbs (with a predilection for the thenar eminence) and subsequently the lower limbs, associated with uni- or bilateral vocal cord paresis leading to hoarse voice and breathing difficulties, and facial weakness.


tibia, hypoplasia or aplasia of, with polydactyly

Tibial hemimelia-polysyndactyly-triphalangeal thumb syndrome is a rare, genetic dysostosis syndrome, with marked inter- and intra-familial variation, typically characterized by triphalangeal thumbs, hand and/or foot polysyndactyly and/or absent/hypoplastic tibiae (associated with duplication of fibulae in some cases), although isolated triphalangeal thumbs have also been reported. It is often accompanied with remarkable short stature and additional features may include radio-ulnar synostosis and hand oligodactyly, as well as abnormal carpal and metatarsal bones.


neuropathy, hereditary sensory and autonomic, type 2A

A hereditary sensory and autonomic neuropathy type 2 characterized by progressive sensory neuropathy with onset in childhood that has material basis in mutation in the HSN2 isoform of the WNK1 gene on chromosome 12p13


multiple system atrophy, cerebellar type

Multiple system atrophy, cerebellar type (MSA-c) is a form of multiple system atrophy (MSA) with predominant cerebellar features (gait and limb ataxia, oculomotor dysfunction, and dysarthria).


frontotemporal dementia, right temporal atrophy variant

Right temporal lobar atrophy (RTLA) is an anatomic variant of frontotemporal dementia (FTD), characterized by behavioral dysfunction, personality changes, episodic memory loss, and prosopagnosia; attributable to an asymmetrical predominantly right-sided, frontotemporal atrophy.


choroidal atrophy-alopecia syndrome

Choroidal atrophy - alopecia is a very rare ectodermal dysplasia syndrome, characterized by the association of choroidal atrophy (sometimes regional), together with other ectodermal dysplasia features including fine and sparse hair, absent or decreased lashes and eyebrows, and possibly mild visual loss and dysplastic/thick/grooved nails.


Pelizaeus-Merzbacher disease, connatal form

The connatal form of Pelizaeus-Merzbacher disease (PMD) is the most severe form of PMD.


visceral botryomycosis

A botryomycosis that involves internal organs such as lungs, liver, or brain. It is a rare disease and has been described mainly in patients with underlying diseases such as diabetes mellitus, cystic fibrosis, or HIV infection. It is most commonly affecting the lungs, although involvement of other organs including liver, spleen, kidney, and brain has also been described.


small cell sarcoma

A sarcoma characterized by the presence of small round or elongated malignant cells with a small amount of cytoplasm.


pediatric myxoid chondrosarcoma

A myxoid chondrosarcoma occurring in children.


urachal diverticulum

Urachal diverticulum is the rarest type of congenital urachal anomaly resulting from the failure of the distal urachus to close at its point of connectivity to the bladder that is usually asymptomatic but can be associated with recurrent urinary tract infections and other complications.


dermatitis herpetiformis

Dermatitis herpetiformis (DH) is a chronic autoimmune subepidermal bullous disease characterized by grouped pruritic lesions such as papules, urticarial plaques, erythema, and herpetiform vesiculae, with a predominantly symmetrical distribution on extensor surfaces of the elbows (90%), knees (30%), shoulders, buttocks, sacral region, and face of children and adults. Erosions, excoriations and hyperpigmentation usually follow. DH may also appear as a consequence of gluten intolerance.


mitochondrial DNA depletion syndrome 7 (hepatocerebral type)

Infantile-onset spinocerebellar ataxia (IOSCA) is a hereditary neurological disorder with early and severe involvement of both the peripheral and central nervous systems. It has only been described in Finnish families.


hereditary sensorimotor neuropathy with hyperelastic skin


food dermatitis

Dermatitis caused by an allergic reaction to ingested food.


hypogonadotropic hypogonadism 10 with or without anosmia

Any hypogonadotropic hypogonadism in which the cause of the disease is a mutation in the TAC3 gene.


qualitative or quantitative defects of delta-sarcoglycan


oculomaxillofacial dysostosis

Oculomaxillofacial dysostosis is a rare, genetic bone developmental disorder characterized by short stature, orbital region and ocular abnormalities (e.g. asymmetric orbits, anophthalmia, down-slanted and S-shaped palpebral fissures, sparse eyebrows/eyelashes, abnormal eyelids, ectropion, symblepharon, corneal leukoma), abnormal nose (e.g. broad and abnormally modeled nasal root, bridge and tip, lateral deviation), malar hypoplasia, cleft lip/palate, and oblique facial clefts. Intellectual disability, microcephaly, micrognathia and limb anomalies (e.g. hemimelia, abnormal scapular girdle, brachydactyly, syndactyly, broad halluces) have also been reported.


autosomal dominant nonsyndromic hearing loss 54

An autosomal dominant nonsyndromic deafness that has material basis in variation in the chromosome region 5q31.


mucopolysaccharidosis-like syndrome with congenital heart defects and hematopoietic disorders


ectasia of the right atrial appendage

Ectasia of the right atrial appendage is a rare cardiac malformation characterized by the enlargement of the right auricle without any other associated cardiac lesions. It can be asymptomatic and diagnosed fortuitously, prenatally or during routine clinical examinations or it can present with heart murmur, palpitation, atrial arrhythmia, fatigue, dyspnea or respiratory distress.


isolated asymptomatic elevation of creatine phosphokinase

Isolated hyperCKemia is a condition characterized by elevated levels of an enzyme called creatine kinase in the blood. In affected individuals, levels of this enzyme are typically 3 to 10 times higher than normal. While elevated creatine kinase often accompanies various muscle diseases, individuals with isolated hyperCKemia have no muscle weakness or other symptoms. Some people with this condition have abnormalities of muscle cells that can be seen with a microscope, such as unusual variability in the size of muscle fibers, but these changes do not affect the function of the muscle.


paramyotonia congenita of Von Eulenburg

Paramyotonia congenita of Von Eulenburg is characterized by exercise- or cold-induced myotonia and muscle weakness. Prevalence is unknown. The syndrome is nonprogressive and is transmitted as an autosomal dominant trait. It is caused by mutations in the gene encoding the alpha subunit of the type IV voltage-gated sodium channel (SCN4A; 17q23.3).


acute myeloid leukemia, loss of chromosome 17p

Any acute myeloid leukemia that has the chromosomal anomaly loss of chromosome 17p. (A cytogenetic abnormality that refers to the loss of all or part of the short arm of chromosome 17 (17p).)


autosomal recessive bestrophinopathy

Autosomal recessive bestrophinopathy (ARB) is a retinal dystrophy, characterized by central visual loss in the first 2 decades of life, associated with an absent electrooculogram (EOG) light rise and a reduced electroretinogram (ERG).


Aase-Smith syndrome

Aase-Smith syndrome type I is a very rare genetic disorder characterized by the following congenital malformations: hydrocephalus (due to Dandy-Walker anomaly), cleft palate, and severe joint contractures.


adult dermatomyositis

Dermatomyositis in an adult.


CERKL-related retinopathy

An inherited retinopathy caused by bi-allelic variants in the CERKL gene.


adult Krabbe disease

A Krabbe disease that occurs in an adult.


infection due to clostridium perfringens


epilepsy, progressive myoclonic, 1B

Any progressive myoclonic epilepsy in which the cause of the disease is a mutation in the PRICKLE1 gene.


lissencephaly with cerebellar hypoplasia type D

Lissencephaly with cerebellar hypoplasia type D (LCHd) is a form of lissencephaly with cerebellar hypoplasia characterized by pronounced microcephaly (at least B1 3 SD), intellectual disability, spastic diplegia and moderate to severe cerebellar hypoplasia involving both vermis and hemispheres.


chromosome 15q24 deletion syndrome

15q24 microdeletion syndrome is a rare chromosomal anomaly characterized cytogenetically by a 1.7-6.1 Mb deletion in chromosome 15q24 and clinically by pre- and post-natal growth retardation, intellectual disability, distinct facial features, and genital, skeletal, and digital anomalies.


mitochondrial encephalomyopathy

A heterogenous group of disorders characterized by alterations of mitochondrial metabolism that result in muscle and nervous system dysfunction. These are often multisystemic and vary considerably in age at onset (usually in the first or second decade of life), distribution of affected muscles, severity, and course. (From Adams et al., Principles of Neurology, 6th ed, pp984-5)


pauci-immune glomerulonephritis with ANCA

Pauci-immune glomerulonephritis (GN) with antineutrophil cytoplasmic antibodies (ANCA) is a form of rapidly progressive GN comprising about 90% of pauci-immune glomerulonephritis, and associated with the presence of circulating ANCA (mostly directed against proteinase-3 (PR3) and myeloperoxidase (MPO)). Patients usually present with hematuria and rapidly declining renal function, often leading to dialysis within weeks without treatment. Cutaneous, pulmonary, musculoskeletal and nervous involvement may be observed in case of systemic disease, and the correlation between ANCA titer and disease activity has been demonstrated.


ulnar hypoplasia-split foot syndrome

Ulnar hypoplasia-split foot syndrome is characterized by the association of severe ulnar hypoplasia, absence of fingers two to five, and split-foot. It has been described in four males belonging to two generations of the same family. X-linked recessive inheritance is suggested, but autosomal dominant transmission cannot be excluded.


neurodevelopmental disorder with dysmorphic facies, impaired speech, and hypotonia


radio-ulnar synostosis-amegakaryocytic thrombocytopenia syndrome

Radio-ulnar synostosis-amegakaryocytic thrombocytopenia syndrome is characterized by the association of proximal fusion of the radius and ulna with congenital amegakaryocytic thrombocytopaenia. Less than 10 cases have been reported in the literature so far. The syndrome is transmitted as an autosomal dominant trait and is caused by mutations in the HOXA11 gene (7p15).


Indian tick typhus

An infectious disease caused by infection with rickettsia conorii subsp. coronorii.


intellectual disability, autosomal recessive 24


Prader-Willi syndrome due to translocation


non-secreting paraganglioma

Non-functioning paraganglioma is a rare neuroendocrine tumor arising from neural crest-derived paraganglion cells (most often in the para-aortic region at the level of renal hilia, organ of Zuckerkandl, thoracic paraspinal region, bladder, and carotid body) not associated with catecholamine secretion. These tumors are usually clinically silent and symptoms, if present, are nonspecific and depend on the location of the tumor. Association with certain hereditary cancer-predisposing syndromes, such as multiple endocrine neoplasia, neurofibromatosis type 1 or von Hippel Lindau syndrome, may be observed.


polycystic kidney disease 4

A autosomal dominant polycystic kidney disease that has material basis in mutation in the PKD4 gene.


extraocular retinoblastoma

Retinoblastoma that has spread beyond the eye e.g. to brain, soft tissue/bone, bone marrow.


hypogonadotropic hypogonadism 3 with or without anosmia

Any hypogonadotropic hypogonadism in which the cause of the disease is a mutation in the PROKR2 gene.


hypothalamic dysfunction

Hypothalamic dysfunction refers to a condition in which the hypothalamus is not working properly. The hypothalamus produces hormones that control body temperature, hunger, moods, release of hormones from many glands such as the pituitary gland, sex drive, sleep, and thirst. The signs and symptoms patients havevary depending on the hormones missing.Anumber of different causes including anorexia, bleeding, genetic disorder, tumors, and more have been linked to hypothalamic dysfunction. Treatment depends on the cause of the hypothalamic dysfunction.


platelet storage pool deficiency

Platelet storage pool deficiency refers to a group of conditions that are caused by problems with the platelet granules. Platelet granules are tiny storage sacs found within the platelets which release various substances to help stop bleeding. Platelet storage pool deficiencies occur when platelet granules are absent, reduced in number, or unable to empty their contents into the bloodstream. The signs and symptoms include frequent nosebleeds; abnormally heavy or prolonged menstruation ; easy bruising; recurrent anemia ; and abnormal bleeding after surgery, dental work or childbirth. Platelet storage pool deficiencies may be genetic or acquired (non-genetic). They can also be part of an inherited genetic syndrome such as Hermansky-Pudlak syndrome, Chediak-Higashi syndrome, thrombocytopenia-absent radius (TAR) syndrome, and Wiskott-Aldrich syndrome. Treatment is symptomatic.


leiomyomatosis

A condition characterized by the presence of numerous small benign smooth muscle neoplasms located throughout the body.


autoinflammatory disease, X-linked

An autoinflammatory syndrome characterized by the onset of systemic autoinflammation in the first months of life. Features include lymphadenopathy, hepatosplenomegaly, fever, panniculitis, and nodular skin rash. Additional manifestations may include inflammation of the optic nerve, intracranial hemorrhage, and lipodystrophy.


hydatidiform mole, recurrent, 1

Any complete hydatidiform mole in which the cause of the disease is a mutation in the NLRP7 gene.


tuberculous empyema

An empyema resulting from infection by Mycobacterium tuberculosis.


congenital absence of thigh and lower leg with foot present, unilateral


arthrogryposis-like hand anomaly-sensorineural deafness syndrome

Arthrogryposis-like hand anomaly-sensorineural deafness syndrome is characterized by an arthrogryposis-like hand anomaly and sensorineural deafness. It has been described in only one family. Male-to-male transmission was observed.


severe neurodegenerative syndrome with lipodystrophy


shoulder and thorax deformity-congenital heart disease syndrome


secondary polycythemia

Secondary polycythemia is an elevated absolute red blood cell mass caused by enhanced stimulation of red blood cell production by an otherwise normal erythroid lineage that may be congenital or acquired (congenital secondary polycythemia and acquired secondary polycythemia).


sex cord-stromal tumor

A neoplasm involving a sex cord.


autosomal recessive nonsyndromic hearing loss 44

Any autosomal recessive nonsyndromic deafness in which the cause of the disease is a mutation in the ADCY1 gene.


vaginal germ cell malignant tumor

A malignant germ cell tumor that involves the vagina.


pinta disease

An endemic bacterial infection caused by Treponema carateum. It is manifested with chronic cutaneous lesions. The early lesions consist of papules and erythematous plaques. The late lesions consist of hypochromic, achromic, hyperpigmented and atrophic lesions. The late skin lesions may cause destruction of bones and cartilage and produce disfiguring changes.


benign neoplasm of buccal mucosa

A benign neoplasm that involves the buccal mucosa.


scrotum melanoma

A melanoma (disease) that involves the scrotum.


laryngeal tuberculosis

Extrapulmonary tuberculosis involving the larynx. Signs and symptoms include hoarseness, cough, and odynophagia. The condition is rare.


harlequin syndrome

Harlequin syndrome (HSD) is an autonomic disorder occurring at any age and characterized by unilateral flushing and sweating, involving the face and sometimes arm and chest, in condition of thermal, exercise or emotional stress without sympathetic ocular manifestations. However, tonic pupils, parasympathetic oculomotor lesion and pre- or postganglionic sudomotor sympathetic deficit can rarely occur.


neurosarcoidosis

A sarcoidosis that involves the nervous system.


X-linked Opitz G/BBB syndrome

X-linked form of Opitz G/BBB syndrome.


LTBP2-related ocular dysgenesis

Any ocular dysgenesis disorder in which the cause of the disease is a mutation in the LTBP2 gene.


spastic paraplegia 89, autosomal recessive


myopathy due to myoadenylate deaminase deficiency

An autosomal recessive condition caused by mutation(s) in the AMPD1 gene, encoding AMP deaminase 1. The condition is characterized by exercise-induced muscle pain and/or fatigue, which may be associated with rhabdomyolysis and/or increased concentrations of creatinine kinase.


ADAM9-related retinopathy

An inherited retinopathy caused by bi-allelic variants in the ADAM9 gene.


MELAS syndrome caused by mutation in MTTH

Any MELAS syndromein which the cause of the disease is a mutation in the MTTH gene.


polyarticular juvenile rheumatoid arthritis


chronic mountain sickness

A pathological condition resulting from chronic exposure to hypoxia at high altitude. The syndrome is characterized by an excessive number of red blood cells associated with a high blood hemoglobin concentration ([Hb]), hypoxemia, and, in some cases, pulmonary hypertension. Clinical signs include headache, fatigue, sleep disturbances, dyspnea, digestive complaints, and high risk of thrombotic events.


intellectual disability-hyperkinetic movement-truncal ataxia syndrome


spinocerebellar ataxia type 32

Spinocerebellar ataxia type 32 (SCA32) is a subtype of autosomal dominant cerebellar ataxia type 1 (ADCA type 1) characterized by ataxia, cognitive impairment and azoospermia in males.


Charcot-Marie-Tooth disease type 4H

Charcot-Marie-Tooth disease, type 4H (CMT4H) is a demyelinating CMT peripheral sensorimotor polyneuropathy


epilepsy, familial focal, with variable foci 1

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


autosomal dominant nonsyndromic hearing loss 31

An autosomal dominant nonsyndromic deafness that has material basis in variation in the chromosome region 6p21.3.


autosomal recessive nonsyndromic hearing loss 79

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


familial recurrent peripheral facial palsy


autoimmune uveitis

An autoimmune form of uveitis (disease).


intermediate malignant teratoma

An immature teratoma characterized by the presence of an intermediate amount of undifferentiated tissues.


facial dermatosis

Facial Dermatosis, also known as facial dermatoses, is related tolipogranulomatosis. An important gene associated with Facial Dermatosis isCCNE1(cyclin E1). The drugsbetamethasoneandbetamethasone acetatehave been mentioned in the context of this disorder.


paternal uniparental disomy of chromosome 6

Paternal uniparental disomy of chromosome 6 is an uniparental disomy of paternal origin characterized by intrauterine growth retardation, transient neonatal diabetes mellitus, and macroglossia.


encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy


tibialis tendinitis

A tendinitis that involves the tibialis.


hypophosphatemic rickets, X-linked recessive

Any X-linked hypophosphatemic rickets in which the cause of the disease is a mutation in the CLCN5 gene.


neoplasm of aortic body

A benign or malignant extra-adrenal parasympathetic paraganglioma that arises from paraganglia adjacent to the base of the heart and great vessels.


chromosome 11 disorder

Chromosomal disorder in which chromosome 11 is affected.


syndromic microphthalmia type 5

Syndromic microphthalmia, type 5 is characterized by the association of a range of ocular anomalies (anophthalmia, microphthalmia and retinal abnormalities) with variable developmental delay and central nervous system malformations.


echinostomiasis

Infection by flukes of the genus Echinostoma.


congenital bilateral absence of vas deferens

Congenital bilateral absence of the vas deferens (CBAVD) is a condition leading to male infertility.


congenital disorder of glycosylation with defective fucosylation 1


inborn vitamin metabolic disorder

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


osteoglophonic dwarfism

Osteoglophonic dwarfism (OGD) is characterized by dwarfism, severe craniofacial abnormalities and multiple unerupted teeth.


autosomal recessive spastic paraplegia type 71


commensal bacterial infectious disease

A bacterial infectious disease that results in infection by bacteria which are part of the normal human flora when one or more of the defense mechanisms designed to restrict them from the usually sterile internal tissues are breached by accident, by intent (surgery), or by an underlying metabolic or an infectious disorder.


GABA aminotransaminase deficiency

Gamma-aminobutyric acid transaminase (GABA-T) deficiency is an extremely rare disorder of GABA metabolism characterized by a severe neonatal-infantile epileptic encephalopathy (manifesting with symptoms such as seizures, hypotonia, hyperreflexia and developmental delay) and growth acceleration.


Sneddon syndrome

Sneddon's syndrome (SS) is a rare non-inflammatory thrombotic vasculopathy characterized by the combination of cerebrovascular disease with livedo racemosa.


hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome


multiple epiphyseal dysplasia, Lowry type

Multiple epiphyseal dysplasia, Lowry type is a rare primary bone dysplasia characterized by small, flat epiphyses (esp. the capital femoral epiphyses), rhizomelic shortening of limbs, cleft of secondary palate, micrognathia, mild joint contractures and facial dysmorphism (incl. mildly upward-slanting palpebral fissures, hypertelorism, broad nasal tip). Additionally reported features include scoliosis, genu valgum, mild pectus excavatum, platyspondyly, dislocated radial heads, brachydactyly, hypoplastic fibulae and talipes equinovarus.


chromosome 19q13.11 deletion syndrome, proximal

Chromosome 19q13.11 deletion syndrome in which the proximal region was deleted.


Q fever

A bacterial infection caused by Coxiella burnetii. It is transmitted to humans by the inhalation of infected air particles or contact with fluids and feces of infected animals. Signs and symptoms include the abrupt onset of fever, headache, myalgias, and weakness.


congenital fibrosarcoma

A fibrosarcoma that occurs in infants. It shares identical morphologic features with adult fibrosarcoma but carries the t(12;15)(p13;q25) translocation that results in ETV6-NTRK3 gene fusion. It usually affects the superficial and deep soft tissues of the extremities. The prognosis is generally much more favorable than for adult fibrosarcoma, and it rarely metastasizes.


catecholaminergic polymorphic ventricular tachycardia 2

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


Ewing sarcoma/peripheral primitive neuroectodermal tumor of bone

A spectrum of malignant tumors arising from the bone and characterized morphologically by the presence of small round cells. Ewing sarcoma and peripheral primitive neuroectodermal tumor represent the ends of a spectrum, with Ewing sarcoma lacking evidence of neural differentiation and the markers that characterize the peripheral primitive neuroectodermal tumor. Ewing sarcoma and peripheral primitive neuroectodermal tumor may share cytogenetic abnormalities, proto-oncogene expression, cell culture and immunohistochemical abnormalities. Pain and the presence of a mass are the most common clinical symptoms.


microcephaly with simplified gyral pattern


cerebellar ataxia-hypogonadism syndrome

Cerebellar ataxia-hypogonadism syndrome is a very rare autosomal recessive neurodegenerative disorder characterized by the combination of progressive cerebellar ataxia with onset from early childhood to the fourth decade, and hypogonadotropic hypogonadism (delayed puberty and lack of secondary sex characteristics). Cerebellar ataxia-hypogonadism syndrome belongs to a clinical continuum of neurodegenerative disorders along with clinically overlapping disorders such as ataxia-hypogonadism-choroidal dystrophy syndrome.


acute myeloid leukemia, t(7;12)(q36;p13)

Any acute myeloid leukemia that has the chromosomal anomaly t(7;12)(q36;p13). (A chromosomal translocation involving the ETV6 gene on chromosome 12p13 and HLXB9 gene on chromosome 7q36.)


carcinoid heart disease

Cardiac manifestation of gastrointestinal CARCINOID TUMOR that metastasizes to the liver. Substances secreted by the tumor cells, including SEROTONIN, promote fibrous plaque formation in ENDOCARDIUM and its underlying layers. These deposits cause distortion of the TRICUSPID VALVE and the PULMONARY VALVE eventually leading to STENOSIS and valve regurgitation.


Ichthyosis-alopecia-eclabion-ectropion-intellectual disability syndrome is an ectodermal dysplasia syndrome characterized by severe generalized lamellar icthyosis at birth with alopecia, eclabium, ectropion and intellectual disability. Although similar to Sjogren-Larsson syndrome, this syndrome lacks the presence of neurologic or macular changes. There have been no further descriptions in the literature since 1987.


neurodevelopmental disorder with craniofacial dysmorphism and skeletal defects


immunodeficiency due to a classical component pathway complement deficiency


paratenonitis

Inflammation of the outer layer of the tendon (paratenon) alone, whether or not the paratenon is lined by synovium.


chromosome 14 disorder

Chromosomal disorder in which chromosome 14 is affected.


acute myeloid leukemia with inv3(p21;q26.2) or t(3;3)(p21;q26.2)

Acute myeloid leukemia with inv(3)(q21;q26.2) or t(3;3)(q21;q26.2) is a subtype of acute myeloid leukemia with recurrent genetic abnormalities characterized by clonal proliferation of myeloid blasts in the bone marrow, blood and, rarely, other tissues. Bone marrow typically shows small, hypolobated megakaryocytes and multilineage dyslplasia. Patients typically present with leukocytosis, anemia, variable platelet counts and a variety of nonspecific symptoms related to ineffective hematopoesis (fatigue, bleeding, bruising, recurrent infections, bone pain) and/or extramedullary site involvement (gingivitis, splenomegaly). High resistance to conventional chemotherapy is reported.


peroxisomal acyl-CoA oxidase deficiency

Peroxisomal acyl-CoA oxidase deficiency is a rare neurodegenerative disorder that belongs to the group of inherited peroxisomal disorders and is characterized by hypotonia and seizures in the neonatal period and neurological regression in early infancy.


HHV-6 encephalitis

HHV-6 encephalitis refers to inflammation of the brain due to an infection with human herpesvirus 6. People who have undergone allogeneic hematopoietic cell transplantation are at an increased risk for developing HHV-6 encephalitis, particularly when umbilical cord blood stem cells are used. People with immune system disorders may also be at an increased risk for developing this infection. Signs and symptoms vary, but often include confusion, anterograde amnesia (difficulty learning new information following the onset of amnesia), short-term memory loss, and seizures.Diagnosis often involves lumbar puncture, virus testing, and MRI. EEG 's may also be recommendedwhen seizures are suspected. HHV-6 encephalitis is treated with an antiviral agent with activity against HHV-6. Long term outlook (chance of full recovery) can vary considerably depending individual patient factors.


ascaridiasis

Infection with nematodes of the genus ascaridia. This condition usually occurs in fowl, often manifesting diarrhea.


dentin caries

A dental caries that involves the dentine.


skeletal dysplasia

Any Mendelian diseases that affects growth and development of the skeleton.


acute panmyelosis with myelofibrosis

An acute myeloid leukemia characterized by bone marrow fibrosis without preexisting primary myelofibrosis.


microcephaly 2, primary, autosomal recessive, with or without cortical malformations


chondroid lipoma

A rare benign adipose tissue neoplasm characterized by nests and cord of abundant univacuolated and multivacuolated lipoblasts and mature adipocytes in a prominent myxoid to hyalinized chondroid matrix admix. It predominantly affects females.


oculomotor nerve cancer

A cancer involving a oculomotor nerve.


bilateral frontal polymicrogyria

Bilateral frontal polymicrogyria is one of the rarest subtypes of polymicrogyria. It is a symmetric and bilateral form (in both brain hemispheres) that only involves the frontal lobes without including the area located behind the Sylvius fissure or the area located behind the Rolando sulcus. Some researchers classify the condition into two different forms: bilateral frontal polymicrogyriaand the bilateral frontoparietal. Signs and symptoms included delayed motor and language milestones; spastic (stiffness) hemiparesis (weakness in one side of the body) or quadriparesis (weakness in all four limbs of the body); and mild to moderate intellectual disability. Seizures mayalsobe present. The frontoparietal form is caused by changes (mutations) in the GPR56 gene but the cause for the frontal form of polymicrogyira is still not known. Treatment is based on the signs and symptoms present in each person.


giant cell tumor

A benign, intermediate, or malignant tumor that arises from the bone or soft tissue. It is characterized by the presence of multinucleated osteoclast-like giant cells.


erythropoietin polycythemia

Polycythemia that is caused by excess erythropoietin.


symphalangism with multiple anomalies of hands and feet

Symphalangism with multiple anomalies of hands and feet is an exceedingly rare syndrome described in one family and characterized by proximal symphalangism and multiple hand and feet disorders (syndactyly, clinodactyly, hypoplasia of the thenar and hypothenar eminences, and a distinctive dermatoglyphic pattern). There have been no further descriptions in the literature since 1981.


fundus pulverulentus

Fundus pulverulentus is a rare form of patterned dystrophy of the retinal pigment epithelium characterized by a granular appearance in the macula, with coarse and punctiform mottling of the retinal pigment epithelium within the macular region. Association with choroidal neovascularization has been reported.


kidney cortex disease

A kidney disease that is located in the kidney cortex.


torsade-de-pointes syndrome with short coupling interval

Torsade-de-pointes (TdP) syndrome with short coupling interval is a very rare variant of Torsade de pointes, a polymorphic ventricular tachycardia, which is characterized by a short coupling interval of the first TdP beat on electrocardiogram in the absence of any structural heart disease. It manifests in early adulthood with syncope, often results in ventricular fibrillation and shows a high risk of sudden cardiac death.


autosomal dominant optic atrophy, classic form

One of the most common forms of hereditary optic neuropathy characterized by progressive bilateral visual loss during the first decade of life, associated with optic disk pallor, visual field and color vision defects.


infratentorial neoplasm

A benign or malignant neoplasm that occurs in brain parenchymal tissue below the tentorium cerebelli.


distal trisomy 7p

Distal trisomy 7p is a rare chromosomal anomaly syndrome, resulting from the partial duplication of the short arm of chromosome 7, with highly variable phenotype typically characterized by severe to profound psychomotor delay, intellectual disability, dysmorphic features (incl. dolichocephaly, microbrachycephaly, high and/or broad forehead, large anterior fontanel, hypertelorism, downslanting palpebral fissures, low-set, dysplastic ears, low, broad and prominent nasal bridge, abnormal palate, micro-/retrognathia), and hypotonia. Cardiovascular, gastrointestinal, skeletal and urogenital anomalies have commonly been reported.


subacute lymphocytic thyroiditis

Thyroiditis associated with painless enlargement of the thyroid gland. It occurs more frequently in females and is characterized by alterations between hyperthyroidism and hypothyroidism and the eventual return to normal thyroid gland function.


hereditary methemoglobinemia

Methemoglobinemia inherited in an autosomal recessive pattern. It is caused by deficiency of the enzyme NADH methemoglobin reductase or the presence of abnormal hemoglobin M. It presents with cyanosis early in life. There is no evidence of cardiopulmonary disease present.


retinitis pigmentosa 1

Any retinitis pigmentosa in which the cause of the disease is a mutation in the RP1 gene.


isolated cerebellar vermis hypoplasia

Isolated cerebellar vermis hypoplasia is a rare, non-syndromic cerebellar malformation characterized by an underdeveloped cerebellar vermis. Patients may present a variable phenotype ranging from normal neurodevelopment to motor and/or language delay, variable degrees of cognitive impairment, hypotonia, equilibrium disturbances, static/dynamic ataxia, oculomotor abnormalities, epilepsy and/or clumsiness. Behavioral disorders such as attention deficit hyperactivity disorder and generalized anxiety have also been reported. Brain MRI may reveal diffuse or selective (mostly posterior) vermian cerebellar hypoplasia and EEG may show focal paroxysms.


lower motor neuron syndrome with late-adult onset


pyosalpinx

The presence of pus in the fallopian tube. It is usually caused by acute salpingitis. The fallopian tube is distended and filled with pus. Histologic examination reveals edema and acute and chronic inflammation. Symptoms include fever, vaginal discharge, and pelvic pain.


hereditary spherocytosis

Hereditary spherocytosis is a congenital hemolytic anemia with a wide clinical spectrum (from symptom-free carriers to severe hemolysis) characterized by anemia, variable jaundice, splenomegaly and cholelithiasis.


Shiga toxin-associated hemolytic uremic syndrome

A rare thrombotic microangiopathy characterized by mechanical hemolytic anemia, thrombocytopenia, and renal dysfunction that is usually associated with prodromal enteritis caused by Shigella dysentriae type 1 or E. Coli.


Charcot-Marie-Tooth disease axonal type 2T

A Charcot-Marie-Tooth disease type 2 that has material basis in homozygous or compound heterozygous mutation in the MME gene on chromosome 3q25.


chromosome 17q21.31 duplication syndrome

The newly described 17q21.31 microduplication syndrome is associated with a broad clinical spectrum, of which behavioral disorders and poor social interaction seem to be the most consistent.


dysostosis

A group of disorders in which the skeletal involvement is predominantly manifested as abnormalities of individual bones or in a group of bones.


myopathy, congenital, with structured cores and z-line abnormalities


mosaic trisomy 21

Trisomy 21 characterized by the presence of an extra chromosome 21 in some of the cells of the organism.


pediatric angiosarcoma

An angiosarcoma occurring in childhood.


familial clubfoot due to 5q31 microdeletion


cartilage cancer

A cancer involving a cartilage tissue.


lichen sclerosus et atrophicus

A chronic inflammatory process affecting the skin. It is characterized by the presence of white, indurated plaques, epidermal atrophy, and fibrosis of the upper dermis. It usually appears in the vulva and penis.


liposarcoma of bone

A very rare malignant adipose tissue neoplasm that arises from the bone.


lethal hemolytic anemia-genital anomalies syndrome

Waters-West syndrome is characterized by the association of lethal non-spherocytic, non-immune hemolytic anemia with abnormalities of the external genitalia (micropenis and hypospadias), flat occiput, dimpled earlobes, deep plantar creases, and increased space between the first and second toes. It has been described only once in two brothers who died a few hours after birth. The second-born infant had massive ascites and hepatosplenomegaly. The mother had two spontaneous abortions (at 6 and 12 weeks gestation) but gave birth to a normal girl, suggesting an autosomal or X-linked recessive mode of inheritance. Although the parents were not known to be consanguineous, they shared a French-Canadian and American Indian ethnic origin.


neurodevelopmental disorder with microcephaly and dysmorphic facies


acute disease

Disease having a short and relatively severe course.


familial thyroid dyshormonogenesis

A type of primary congenital hypothyroidism, a permanent thyroid hormone deficiency that is present from birth, which results from inborn errors of thyroid hormone synthesis.


mild hypophosphatasia

Mild hypophosphatasia is the most common form of hypophosphatasia characterized by low alkaline phosphatase, unspecific clinical signs, and typically presents in individuals in adulthood.


PEHO-like syndrome

PEHO-like syndrome is a rare, genetic neurological disease characterized by progressive encephalopathy, early-onset seizures with a hypsarrhythmic pattern, facial and limb edema, severe hypotonia, early arrest of psychomotor development and craniofacial dysmorphism (evolving microcephaly, narrow forehead, short nose, prominent auricles, open mouth, micrognathia), in the absence of neuro-ophthalmic or neuroradiologic findings. Poor visual responsiveness, growth failure and tapering fingers are also associated.


heterotopia, periventricular, X-linked dominant


Wiedemann-Rautenstrauch syndrome

Wiedemann-Rautenstrauch syndrome is a very rare disorder with features of premature aging recognizable at birth, decreased subcutaneous fat, hypotrichosis, relative macrocephaly and dysmorphism.


benign neoplasm of hard palate

A benign neoplasm that involves the hard palate.


pain agnosia

Loss of the ability to perceive and process pain.


cervical hypertrichosis-peripheral neuropathy syndrome

Cervical hypertrichosis peripheral neuropathy is a rare syndrome characterized by the association of congenital hypertrichosis in the anterior cervical region with peripheral sensory and motor neuropathy. It has been described in three members of the same family and in one unrelated boy. Associated features in the familial cases include retinal anomalies, spina bifida, kyphoscoliosis and hallux valgus, while that in the non-familial case includes developmental delay. An autosomal recessive mode of inheritance is suggested. There have been no further descriptions in the literature since 1993.


calcaneonavicular coalition

A synostosis characterized by the fusion of carpal and tarsal bones, which causes stiffness and immobility of the hands and the feet.


qualitative or quantitative defects of alphaB-cristallin


severe combined immunodeficiency due to CTPS1 deficiency

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


lethal Kniest-like dysplasia

Lethal Kniest-like dysplasia is a severe lethal skeletal dysplasia. It has been described in two sibs (one male and one female) born to nonconsanguineous parents. It is characterized by dumbbell-shaped long bones with markedly shortened diaphyses and metaphyseal irregularities.


corticobasal syndrome

Corticobasal syndrome (CBS) is a rare neurodegenerative disease characterized by multifaceted motor system dysfunctions and cognitive defects such as asymmetric rigidity, bradykinesia, limb apraxia, and visuospatial dysfunction.


tetraploidy syndrome

The presence of four sets of chromosomes. It is associated with abnormalities, multiple; and miscarrages.


juvenile-onset Steinert myotonic dystrophy


retinitis pigmentosa 87 with choroidal involvement


class V glucose-6-phosphate dehydrogenase deficiency


DNA repair disease

A disease that has its basis in the disruption of DNA repair.


pontocerebellar hypoplasia type 9

Any non-syndromic pontocerebellar hypoplasia in which the cause of the disease is a mutation in the AMPD2 gene.


hypoxanthine guanine phosphoribosyltransferase partial deficiency

Kelley-Seegmiller syndrome (KSS) is the mildest form of hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency, a hereditary disorder of purine metabolism, and is associated with uric acid overproduction (UAO) leading to urolithiasis, and early-onset gout.


isolated cryptophthalmia

Isolated cryptophtalmia is a congenital abnormality in which the eyelids are absent and skin covers the ocular bulb, which is often microphthalmic. Six cases of complete bilateral crytophthalmia have been described. Transmission is autosomal dominant.


developmental and epileptic encephalopathy, 15


Schimke immuno-osseous dysplasia

A multisystem disorder characterized by spondyloepiphyseal dysplasia and disproportionate short stature, facial dysmorphism, T-cell immunodeficiency, and glomerulonephritis with nephrotic syndrome.


refractory plasma cell neoplasm

A plasma cell neoplasm that is resistant to treatment.


kleptomania

A disorder characterized by the recurrent failure to resist the impulse to steal items of little intrinsic value; the individual experiences a rising subjective sense of tension before the theft and a sense of gratification or relief during the theft.


exercise-induced anaphylaxis

A rare disorder in which anaphylaxis occurs in association with physical activity.


granulomatous dermatitis

An inflammatory reaction of the skin to various organic and inorganic antigens. It is characterized by tumor-like masses or nodules of granulomatous tissue comprised of activated histiocytes, epitheliod cells, and multinucleated giant cells.


behavioral variant of frontotemporal dementia

Behavioral variant of frontotemporal dementia (bv-FTD) is a form of frontotemporal dementia (FTD), characterized by progressive behavioral impairment and a decline in executive function with frontal lobe-predominant atrophy.


Gaucher disease type II

Gaucher disease type 2 is the acute neurological form of Gaucher disease (GD). It is characterized by early-onset and severe neurological involvement of the brainstem, associated with an organomegaly and generally leading to death before the age of 2.


inherited blood coagulation disorder

Hemorrhagic and thrombotic disorders that occur as a consequence of inherited abnormalities in blood coagulation.


phocomelia, Schinzel type

Schinzel phocomelia syndrome, also called limb/pelvis hypoplasia/aplasia syndrome, is characterized by skeletal malformations affecting the ulnae, pelvic bones, fibulae and femora. As the phenotype is similar to that described in the malformation syndrome known as Al-Awadi/Raas-Rothschild syndrome, they are thought to be the same disorder.


inclusion body myositis

A slowly progressive degenerative inflammatory disorder of skeletal muscles characterized by late onset weakness of specific muscles and distinctive histopathological features.


autosomal dominant nonsyndromic hearing loss 10

Any autosomal dominant nonsyndromic deafness in which the cause of the disease is a mutation in the EYA4 gene.


infantile systemic hyalinosis

Infantile systemic hyalinosis (ISH) is a very rare disorder belonging to the heterogeneous group of genetic fibromatoses and is characterized by progressive joint contractures, skin abnormalities, severe chronic pain and widespread deposition of hyaline material in many tissues such as the skin, skeletal muscle, cardiac muscle, gastrointestinal tract, lymph nodes, spleen, thyroid, and adrenal glands.


intellectual disability, X-linked, syndromic, 35


microcephaly 6 with or without short stature

Disorder of fetal brain growth; individuals have small brains and almost always have mental retardation, although rare individuals with mild microcephaly (-3 SD) and normal intelligence have been reported. Clinical features include the features of ‘microcephaly 6, primary, autosomal recessive’ and 'Seckel syndrome', and may include short stature or mild seizures.


substernal goiter

An enlarged thyroid gland with at least 50% of the gland situated behind the sternum. It is an unusual presentation of an intrathoracic goiter. Substernal goiters frequently cause compression on the trachea leading to deviation, narrowing, and respiratory symptoms.


aortic aneurysm, familial thoracic 4

Any familial thoracic aortic aneurysm and aortic dissection in which the cause of the disease is a mutation in the MYH11 gene.


Dedifferentiated liposarcoma

Dedifferentiated liposarcoma (DDLS) is a high-grade subtype of liposarcoma (LS) that progresses from well-differentiated liposarcoma (WDLS), and most often occurs in the retroperitoneum. It is defined as a region of nonlipogenic sarcoma associated with WDLS.


X-linked intellectual disability-short stature-overweight syndrome is a multiple congenital anomalies syndrome characterized by borderline to severe intellectual disability, speech delay, short stature, elevated body mass index, a pattern of truncal obesity (reported in older males), and variable neurologic features (e.g. hypotonia, tremors, gait disturbances, behavioral problems, and seizure disorders). Less common manifestations include microcephaly, microorchidism and/or microphallus. Dysmorphic features have been reported in some patients but no consitent pattern has been noted.


primary ciliary dyskinesia 22

Any primary ciliary dyskinesia in which the cause of the disease is a mutation in the ZMYND10 gene.


non-syndromic brachydactyly of toes

A non-syndromic brachydactyly that involves the pes.


retinitis pigmentosa 55

Any retinitis pigmentosa in which the cause of the disease is a mutation in the ARL6 gene.


Dahlberg-Borer-Newcomer syndrome

Dahlberg-Borer-Newcomer syndrome is a very rare ectodermal dysplasia syndrome, described in 2 adult brothers, characterized by the association of hypoparathyroidism, nephropathy, congenital lymphedema, mitral valve prolapse and brachytelephalangy. Additional features include mild facial dysmorphism, hyperthricoses, and nail abnormalities.


mitochondrial complex 3 deficiency, nuclear type 10


Phosphoribosylpyrophosphate (PRPP) synthetase superactivity is an X-linked disorder of purine metabolism associated with hyperuricemia and hyperuricosuria, comprised of two forms: an early-onset severe form characterized by gout, urolithiasis, and neurodevelopmental anomalies (severe PRPP synthetase superactivity) and a mild late-onset form with no neurologic involvement (mild PRPP synthetase superactivity).


sialuria

Sialuria is an extremely rare metabolic disorder described in fewer than 10 patients to date and characterized by variable signs and symptoms, mostly in infancy, including transient failure to thrive, slightly prolonged neonatal jaundice, equivocal or mild hepatomegaly, microcytic anemia, frequent upper respiratory infections, gastroenteritis, dehydration and flat and coarse facies. Learning difficulties and seizures may occur in childhood.


short QT syndrome type 2

Any short QT syndrome in which the cause of the disease is a mutation in the KCNQ1 gene.


cone dystrophy 4

Any cone dystrophy in which the cause of the disease is a mutation in the PDE6C gene.


familial hemophagocytic lymphohistiocytosis 4

Any genetic hemophagocytic lymphohistiocytosis in which the cause of the disease is a mutation in the STX11 gene.


fibrochondrogenesis

Fibrochondrogenesis is a rare, neonatally lethal, rhizomelic chondrodysplasia. Eleven cases have been reported. The face is distinctive and characterized by protuberant eyes, flat midface, flat small nose with anteverted nares and a small mouth with long upper lip. Cleft palate, micrognathia and bifid tongue can occur. The limbs show marked shortness of all segments with relatively normal hands and feet. No internal anomalies other than omphalocele have been reported. Transmission is probably autosomal recessive. Recurrence in a consanguineous family (affecting both sexes) and concordance of affected male twins have been reported.


neurocutaneous melanocytosis

Neurocutaneous melanocytosis (NCM) is a rare congenital neurological disorder characterized by abnormal aggregations of nevomelanocytes within the central nervous system (leptomeningeal melanocytosis) associated with large or giant congenital melanocytic nevi (CMN). NCM can be asymptomatic or present as variably severe and progressive neurological impairment, sometimes resulting in death.


chromosome 16 disorder

Chromosomal disorder in which chromosome 16 is affected.


qualitative or quantitative defects of perlecan


primary laryngeal lymphangioma

Primary laryngeal lymphangioma is a rare, benign, congenital malformation of the lymphatic system characterized by a polypoidal, variable-sized, soft tissue mass located in the larynx. Most lesions manifest by the 2nd year of life and, depending on the size, patients may present with changes in voice, dysphagia, stridor, airway obstruction and/or respiratory distress. Cystic hygroma of the neck is frequently associated.


intellectual disability, X-linked 103

Any non-syndromic X-linked intellectual disability in which the cause of the disease is a mutation in the KLHL15 gene.


torsion dystonia 4

DYT4 type primary dystonia is characterized by predominantly laryngeal dystonia (manifesting as whispering dysphonia) and cervical dystonia (manifesting as torticollis).


homocystinuria due to methylene tetrahydrofolate reductase deficiency

Homocystinuria due to methylene tetrahydrofolate reductase (MTHFR) deficiency is a metabolic disorder characterized by neurological manifestations.


lipoma of face

A lipoma that involves the face.


granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2

Any chronic granulomatous disease in which the cause of the disease is a mutation in the NCF2 gene.


brain malformations with or without urinary tract defects

A brain disorder caused by pathogenic variants in NFIA that is characterized by developmental delay, corpus callosum agenesis/hypoplasia and craniofacial dysmorphism, such as macrocephaly (caused by hydrocephalus or ventriculomegaly), low-set ears, anteverted nostrils and micrognathia. Urinary tract defects (e.g. vesicoureteral reflux, urinary incontinence) are also frequently associated. Other reported variable manifestations include hypotonia, tethered spinal cord, Chiari type I malformation and seizures.


hereditary Wilms tumor

Familial embryonal neoplasm derived from nephrogenic blastemal cells. Several lines of differentiation, including blastemal, stromal and epithelial, are usually expressed. Comprises approximately 1% of Wilms tumors. (AFIP fascicle version 2.0)


conventional leiomyosarcoma

An uncommon, aggressive malignant smooth muscle neoplasm. It is characterized by the presence of atypical large spindle or round cells, nuclear palisading, tumor cell necrosis, mitotic figures and may be associated with vascular invasion.


ulna hypoplasia-intellectual disability syndrome

Ulna hypoplasia - intellectual deficit is a very rare syndrome characterized by mesomelic shortness of the forearms, bilateral clubfeet, aplasia or hypoplasia of all nails and severe psychomotor retardation.


Angelman syndrome due to imprinting defect in 15q11-q13


complex cortical dysplasia with other brain malformations 2

Any complex cortical dysplasia with other brain malformations in which the cause of the disease is a mutation in the KIF5C gene.


Prader-Willi syndrome due to imprinting mutation


kidney liposarcoma

A rare malignant adipose tissue neoplasm of the fat cells surrounding the kidney, usually of the well-differentiated or myxoid type. It may be associated with tuberous sclerosis.