hereditary fructose intolerance

Hereditary fructose intolerance (HFI) is an autosomal recessive disorder of fructose metabolism, resulting from a deficiency of hepatic fructose-1-phosphate aldolase activity and leading to gastrointestinal disorders and postprandial hypoglycemia following fructose ingestion. HFI is a benign condition when treated, but it is life-threatening and potentially fatal if left untreated.


fucosidosis

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Fucosidosis is an extremely rare lysosomal storage disorder characterized by a highly variable phenotype with common manifestations including neurologic deterioration, coarse facial features, growth retardation, and recurrent sinopulmonary infections, as well as seizures, visceromegaly, angiokeratoma and dysostosis.


classic galactosemia

Classic galactosemia is a life-threatening metabolic disease with onset in the neonatal period. Infants usually develop feeding difficulties, lethargy, and severe liver disease.


gastroschisis

Gastroschisis is marked by viscera protruding, without a covering sac, from the fetal abdomen on the right lateral base of the umbilicus. It is due to defective embryo growth and other malformations are only exceptionally associated.


Gaucher disease type I

Gaucher disease type 1 is the chronic non-neurological form of Gaucher disease (GD) characterized by organomegaly, bone involvement and cytopenia.


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.


Gaucher disease type III

Gaucher disease type 3 is the subacute neurological form of Gaucher disease (GD) characterized by progressive encephalopathy and associated with the systemic manifestations (organomegaly, bone involvement, cytopenia) of GD type 1.


glycogen storage disease due to glucose-6-phosphatase deficiency type IA

Glycogenosis due to glucose-6-phosphatase deficiency (G6P) type a, or glycogen storage disease (GSD) type 1a, is a type of glycogenosis due to G6P deficiency.


glycogen storage disease Ib

A type of glycogenosis due to G6P deficiency.


glycogen storage disease II

Glycogen storage disease due to acid maltase deficiency (AMD) is an autosomal recessive trait leading to metabolic myopathy that affects cardiac and respiratory muscles in addition to skeletal muscle and other tissues. AMD represents a wide spectrum of clinical presentations caused by an accumulation of glycogen in lysosomes: Glycogen storage disease due to acid maltase deficiency, infantile onset, non-classic infantile onset and adult onset. Early onset forms are more severe and often fatal.


glycogen storage disease due to glycogen branching enzyme deficiency

Glycogen branching enzyme (GBE) deficiency (Andersen's disease or amylopectinosis), or glycogen storage disease type 4 (GSD4), is a rare and severe form of glycogen storage disease which accounts for approximately 3% of all the glycogen storage diseases.


glycogen storage disease V

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


glycogen storage disease VII

Muscle phosphofructokinase (PFK) deficiency (Tarui's disease), or glycogen storage disease type 7 (GSD7), is a rare form of glycogen storage disease characterized by exertional fatigue and muscular exercise intolerance. It occurs in childhood.


anti-glomerular basement membrane disease

An autoimmune disease that affects the lungs and kidneys and is characterized by pulmonary alveolar hemorrhage (bleeding in the lungs) and a kidney disease known as glomerulonephritis. Some use the term 'Goodpasture syndrome' for the findings of glomerulonephritis and pulmonary hemorrhage and the term 'Goodpasture disease' for those patients with glomerulonephritis, pulmonary hemorrhage, and anti-GBM antibodies. Currently, the preferred term for both conditions is “ anti-GBM antibody disease ”. Circulating antibodies are directed against the collagen of the part of the kidney known as the glomerular basement membrane (GBM), resulting in acute or rapidly progressive glomerulonephritis. Antibodies also attack the collagen of the air sacs of the lung (alveoli) resulting in bleeding of the lung (pulmonary hemorrhage). Symptoms may include general body discomfort or pain, bleeding from the nose and/or blood in the urine, respiratory problems, anemia, chest pain, and kidney failure. Anti-GBM disease is thought to result from an environmental insult (smoking, infections, exposure to certain drugs) in a person with genetic susceptibility, such as a specific human leukocyte antigen (HLA) type. Diagnosis is confirmed with the presence of anti-GBM antibody in the blood or in the kidney. The treatment of choice is plasmapheresis in conjunction with prednisone and cyclophosphamide.


Pantothenate kinase-associated neurodegeneration (PKAN) is the most common type of neurodegeneration with brain iron accumulation (NBIA), a rare neurodegenerative disorder characterized by progressive extrapyramidal dysfunction (dystonia, rigidity, choreoathetosis), iron accumulation on the brain and axonal spheroids in the central nervous system.


congenital heart block

Heart block that occurs on or before 28 days of life.


congenital hematological disorder

A disorder of the blood that is present at birth.


classic Hodgkin lymphoma

Classical Hodgkin lymphoma (CHL) is a B-cell lymphoma characterized histologically by the presence of large mononuclear Hodgkin cells and multinucleated Reed-Sternberg (HRS) cells.


classic homocystinuria

Classical homocystinuria due to cystathionine beta-synthase (CbS) deficiency is characterized by the multiple involvement of the eye, skeleton, central nervous system, and vascular system.


hydrocephalus, nonsyndromic, autosomal recessive 1

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


normal pressure hydrocephalus

A form of compensated hydrocephalus characterized clinically by a slowly progressive gait disorder (see gait disorders, neurologic), progressive intellectual decline, and urinary incontinence. Spinal fluid pressure tends to be in the high normal range. This condition may result from processes which interfere with the absorption of csf including subarachnoid hemorrhage, chronic meningitis, and other conditions. (From Adams et al., Principles of Neurology, 6th ed, pp631-3)


familial lipoprotein lipase deficiency

Familial lipoprotein lipase deficiency is a rare genetic disorder is which a person lacks the enzyme lipoprotein lipase, a protein needed to break down fat molecules. Deficiency of this enzyme prevents affected individuals from properly digesting certain fats. This results in the accumulation of fatty droplets called chylomicrons in the blood and an increase in the blood concentration of triglycerides. Symptoms include episodes of abdominal pain, recurrent inflammation of the pancreas (pancreatitis), abnormal enlargement of the liver and/or spleen (hepatosplenomegaly), and the development of skin lesions known as erruptive xanthomas. Familial lipoprotein lipase deficiency is caused by changes (mutations) in the LPL gene. It is inherited in an autosomal recessive pattern. Treatment aims to control symptoms and blood triglyceride levels with a very low-fat diet. Treatment for individual symptoms (i.e. pancreatitis) involves following established treatment guidelines.


autoimmune polyendocrine syndrome type 1

Autoimmune polyendocrinopathy type 1, or APECED syndrome, is a genetic disease that manifests in childhood or early adolescence with a combination of chronic mucocutaneous candidiasis, hypoparathyroidism and autoimmune adrenal failure.


scurvy

A condition that develops in people who do not consume an adequate amount of vitamin C in their diet. Although scurvy is relatively rare in the United States, it continues to be a problem in malnourished populations around the world (such as impoverished, underdeveloped third world countries). Early features of the condition include general weakness, fatigue and aching limbs. If left untreated, more serious problems can develop such as anemia, gum disease, and skin hemorrhages. Symptoms generally develop after at least 3 months of severe or total vitamin C deficiency. Scurvy can be cured with vitamin C supplements taken by mouth. Once recovery is complete, dietary modifications to ensure the 'recommended daily intake' of vitamin C is reached will prevent relapse. Except in the case of severe dental disease, permanent damage from scurvy does not usually occur.


Sanjad-Sakati syndrome (SSS), also known as hypoparathyroidism - intellectual disability-dysmorphism, is a rare multiple congenital anomaly syndrome, mainly occurring in the Middle East and the Arabian Gulf countries, characterized by intrauterine growth restriction at birth, microcephaly, congenital hypoparathyroidism (that can cause hypocalcemic tetany or seizures in infancy), severe growth retardation, typical facial features (long narrow face, deep-set eyes, beaked nose, floppy and large ears, long philtrum, thin lips and micrognathia), and mild to moderate intellectual deficiency. Ocular findings (i.e. nanophthalmos, retinal vascular tortuosity and corneal opacification/clouding) and superior mesenteric artery syndrome have also been reported. Although SSS shares the same locus with the autosomal recessive form of Kenny-Caffey syndrome, the latter differs from SSS by its normal intelligence and skeletal features.


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.


pseudotumor cerebri

Idiopathic intracranial hypertension is a neurological disorder characterized by isolated increased intracranial pressure manifesting with recurrent and persistent headaches, nausea, vomiting, progressive and transient obstruction of the visual field, papilledema. Visual loss can be irreversible.


combined immunodeficiency due to DOCK8 deficiency

Combined immunodeficiency due to dedicator of cytokinesis 8 protein (DOCK8) deficiency is a form of T and B cell immunodeficiency characterized by recurrent cutaneous viral infections, susceptibility to cancer and elevated serum levels of immunoglobulin E (IgE).


Krabbe disease

A lysosomal disorder that affects the white matter of the central and peripheral nervous systems. It includes infantile, late-infantile/juvenile and adult forms.


Landau-Kleffner syndrome

Landau-Kleffner syndrome (LKS) is a rare neurological syndrome characterized by the sudden or gradual development of aphasia (the inability to understand or express language) and recurrent seizures (epilepsy). Children with LKS typically develop normally until signs and symptoms of the syndrome begin to develop between age 2 and 8 years. Males are more often affected by LKS than females. In about 20% of people with LKS, mutations (changes) in the GRIN2A gene have been identified. The syndrome is inherited in an autosomal dominant manner. In other cases, the syndrome may be caused by changes to other unidentified genes. LKS is diagnosed when a doctor sees clinical features that are consistent with the syndrome such as a loss of speech and an electroencephalogram (EEG) that shows specific kinds of seizure activity. Genetic testing can be used to confirm if there is a mutation in GRIN2A, but this testing is not done routinely. Treatment for LKS usually consists of medications such as anticonvulsants and corticosteroids to help prevent seizures. Speech therapy should also be started promptly in order to ensure the best long-term outlook for children with LKS.


Norum disease

A form of lecithin-cholesterol acyltransferase deficiency (LCAT) characterized clinically by corneal opacities, hemolytic anemia, and renal failure, and biochemically by severely decreased HDL cholesterol and complete deficiency of the LCAT enzyme.


lymphoid interstitial pneumonia

Interstitial pneumonia characterized by the presence of bibasilar pulmonary interstitial infiltrates composed of lymphocytes and plasma cells. It may be associated with autoimmune and lymphoproliferative disorders. Signs and symptoms include fever, cough, and dyspnea. Symptomatic patients may require immunosuppressive treatment.


severe early-childhood-onset retinal dystrophy

Severe early childhood onset retinal dystrophy (SECORD) is an inherited retinal dystrophy, characterized by a severe congenital night blindness, progressive retinal dystrophy and nystagmus. Best corrected visual acuity can reach 0.3 in the first decade of life and can pertain well into the second decade of life. Blindness is often complete by the age of 30 years. An overlap with Leber congenital amaurosis (LCA) occurs when patients are characterized by their visual acuity and panretinal dystrophy.


alpha-mannosidosis

Alpha-mannosidosis is an inherited lysosomal storage disorder characterized by immune deficiency, facial and skeletal abnormalities, hearing impairment, and intellectual deficit.


maple syrup urine disease

An autosomal recessive inherited disorder caused by mutations in the BCKDHA, BCKDHB, DBT, and DLD genes. It is characterized by a deficiency of branched-chain alpha-keto acid dehydrogenase complex, leading to accumulation of metabolites in the body fluids. The name of the disease derives from the sweet odor of the urine in infants, reminiscent of maple syrup. Signs and symptoms usually appear in infancy and include lethargy and developmental delays. If untreated, it may lead to seizures, coma, and death.


Langer mesomelic dysplasia

Langer mesomelic dysplasia (LMD) is characterized by severe disproportionate short stature with mesomelic and rhizomelic shortening of the upper and lower limbs.


metachromatic leukodystrophy, juvenile form

Metachromatic leukodystrophy is an inherited condition characterized by the accumulation of fats called sulfatides in cells, especially cells of the nervous system. This accumulation results in progressive destruction of white matter of the brain, which consists of nerve fibers covered by myelin.Affected individuals experience progressive deterioration of intellectual functions and motor skills, such as the ability to walk. They also develop loss of sensation in the extremities, incontinence, seizures, paralysis, inability to speak, blindness, and hearing loss. Eventually they lose awareness of their surroundings and become unresponsive. This condition is inherited in an autosomal recessive pattern and is caused by mutations in the ARSA and PSAP genes.


Nijmegen breakage syndrome

Nijmegen breakage syndrome is a rare genetic disease presenting at birth with microcephaly, dysmorphic facial features, becoming more noticeable with age, growth delay, and later-onset complications such as malignancies and infections.


inborn mitochondrial myopathy

Myopathy caused by mitochondrial abnormalities.


sulfite oxidase deficiency due to molybdenum cofactor deficiency type A

An autosomal recessive condition that is caused by mutation(s) in the MOCS1 gene, encoding molybdenum cofactor biosynthesis protein 1. it is characterized by poor feeding, encephalopathy, seizures and dysmorphic facial features.


mucolipidosis type II

Mucolipidosis II (MLII) is a slowly progressive lysosomal disorder characterized by growth retardation, skeletal abnormalities, facial dysmorphism, stiff skin, developmental delay and cardiomegaly.


mucopolysaccharidosis type 3A

A rare autosomal recessive lysosomal storage disease caused by deficiency of the enzyme heparan sulfate sulfatase. It is characterized by behavioral changes, sleep disturbances, mental developmental delays and seizures.


mucopolysaccharidosis type 3B

A rare autosomal recessive lysosomal storage disease caused by deficiency of the enzyme N-acetyl-alpha-D-glucosaminidase. It is characterized by behavioral changes, sleep disturbances, and mental developmental delays.


mucopolysaccharidosis type 4A

A rare autosomal recessive lysosomal storage disease caused by deficiency of the enzyme galactosamine-6-sulfatase. It is characterized by skeletal and central nervous system deficits.


mucopolysaccharidosis type 6

Mucopolysaccharidosis type 6 (MPS 6) is a lysosomal storage disease with progressive multisystem involvement, associated with a deficiency of arylsulfatase B (ASB) leading to the accumulation of dermatan sulfate.


mucopolysaccharidosis type 7

Mucopolysaccharidosis type VII (MPS VII) is a very rare lysosomal storage disease belonging to the group of mucopolysaccharidoses.


spinal muscular atrophy, type 1

A severe infantile form of proximal spinal muscular atrophy characterized by severe and progressive muscle weakness and hypotonia resulting from the degeneration and loss of the lower motor neurons in the spinal cord and the brain stem nuclei.


spinal muscular atrophy, type III

Proximal spinal muscular atrophy type 3 (SMA3) is a relatively mild form of proximal spinal muscular atrophy characterized by muscle weakness and hypotonia resulting from the degeneration and loss of the lower motor neurons in the spinal cord and the brain stem nuclei.


spinal muscular atrophy, type II

Proximal spinal muscular atrophy type 2 (SMA2) is a chronic infantile form of proximal spinal muscular atrophy characterized by muscle weakness and hypotonia resulting from the degeneration and loss of the lower motor neurons in the spinal cord and the brain stem nuclei.


autosomal recessive limb-girdle muscular dystrophy type 2B

Autosomal recessive limb-girdle muscular dystrophy type 2B (LGMD2B) is a subtype of autosomal recessive limb-girdle muscular dystrophy characterized by an onset in late adolescence or early adulthood of slowly progressive, proximal weakness and atrophy of shoulder and pelvic girdle muscles. Cardiac and respiratory muscles are not involved. Hypertrophy of the calf muscles and highly elevated serum creatine kinase levels are frequently observed.


Miyoshi myopathy

A distal myopathy, characterized by weakness in the distal lower extremity posterior compartment (gastrocnemius and soleus muscles) and associated with difficulties in standing on tip toes.


myasthenia gravis

Myasthenia gravis (MG) is a rare, clinically heterogeneous, autoimmune disorder of the neuromuscular junction characterized by fatigable weakness of voluntary muscles.


mycosis fungoides

Classical mycosis fungoides is the most common type of mycosis fungoides (MF), a form of cutaneous T-cell lymphoma, and is characterized by slow progression from patches to more infiltrated plaques and eventually to tumors.


primary myelofibrosis

Myelofibrosis with myeloid metaplasia is a myeloproliferative disease with annual incidence of approximately 1 case per 100,000 individuals and age at diagnosis around 60 (an increased prevalence is noted in Ashkenazi Jews). Clinical manifestations depend on the type of blood cell affected and may include anemia, pallor, splenomegaly, hypermetabolic state, petechiae, ecchymosis, bleeding, lymphadenopathy, hepatomegaly, portal hypertension.


plasma cell myeloma

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


Unverricht-Lundborg syndrome

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


Thomsen and Becker disease

A rare, genetic, skeletal muscle channelopathy characterized by slow muscle relaxation after contraction (myotonia).


Leigh syndrome

A progressive neurological disease defined by specific neuropathological features associating brainstem and basal ganglia lesions.


Netherton syndrome

Netherton syndrome (NS) is a skin disorder characterized by congenital ichthyosiform erythroderma (CIE), a distinctive hair shaft defect (trichorrhexis invaginata; TI) and atopic manifestations.


Niemann-Pick disease, type C1

Type C Niemann-Pick disease associated with a mutation in the gene NPC1, encoding Niemann-Pick C1 protein.


cystic hygroma

A benign lymphatic neoplasm usually arising from the neck and characterized by cystic dilation of the lymphatic vessels.


obesity-hypoventilation syndrome

Hypoventilation syndrome in very obese persons with excessive adipose tissue around the abdomen and diaphragm is characterized by diminished to absent ventilatory chemoresponsiveness; chronic hypoxia; hypercapnia; polycythemia; and long periods of sleep during day and night (hypersomnolence). It is a condition often related to obstructive sleep apnea but can occur separately.


ocular motor apraxia, Cogan type

Ocular motor apraxia, Cogan type is characterized by impairment of voluntary horizontal eye movements and compensatory head thrust. Around 50 cases have been described so far. The oculomotor manifestations tend to improve with age but the syndrome may also be associated with learning and speech difficulties, or, in some cases, cerebral malformations. Both sporadic and familial forms have been described, with sporadic forms being more frequent. The mode of transmission of the familial form has not yet been clearly established. A gene located on the long arm of chromosome 2, near to the NPHP1 gene involved in nephronophthisis, may be associated with ocular motor apraxia, Cogan type.


orotic aciduria

An extremely rare autosomal recessive inherited disorder caused by mutations in the UMPS gene. It is characterized by deficiency of the activity of the pyrimidine pathway enzyme uridine 5'-monophosphate (UMP) synthase. Clinical manifestations include growth retardation, anemia, and increased excretion of orotic acid in the urine.


osteogenesis imperfecta type 3

Osteogenesis imperfecta type III is a severe type of osteogenesis imperfecta (OI), a genetic disorder characterized by increased bone fragility, low bone mass and susceptibility to bone fractures. The main signs of type III include very short stature, a triangular face, severe scoliosis, grayish sclera, and dentinogenesis imperfecta (DI).


osteosarcoma

A usually aggressive malignant bone-forming mesenchymal neoplasm, predominantly affecting adolescents and young adults. It usually involves bones and less frequently extraosseous sites. It often involves the long bones (particularly distal femur, proximal tibia, and proximal humerus). Pain with or without a palpable mass is the most frequent clinical symptom. It may spread to other anatomic sites, particularly the lungs.


osteoporosis-pseudoglioma syndrome

Osteoporosis pseudoglioma syndrome is a very rare autosomal recessive disorder characterized by congenital or infancy-onset blindness and severe juvenile-onset osteoporosis and spontaneous fractures.


primary hyperoxaluria type 1

A rare disorder of glyoxylate metabolism characterized by the accumulation of oxalate due to a deficiency of the peroxisomal hepatic enzyme L-alanine: glyoxylate aminotransferase (AGT). Clinical presentation is variable, ranging from occasional symptomatic nephrolithiasis to nephrocalcinosis and end-stage renal disease with systemic involvement.


primary hyperoxaluria type 2

Primary hyperoxaluria (PH) type 2 is a rare disorder of glyoxylate metabolism caused by the deficiency of the enzyme glyoxylate reductase/hydropyruvate reductase (GR/HPR) characterized by a childhood onset with clinical manifestations that include recurrent nephrolithiasis, nephrocalcinosis and end-stage renal disease with subsequent systemic oxalosis.


malignant pancreatic neoplasm

A malignant neoplasm involving the pancreas.


Shwachman-Diamond syndrome

Shwachman-Diamond syndrome (SDS) is a rare multisystemic syndrome characterized by chronic and usually mild neutropenia, pancreatic exocrine insufficiency associated with steatorrhea and growth failure, skeletal dysplasia with short stature, and an increased risk of bone marrow aplasia or leukemic transformation.


d-bifunctional protein deficiency

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


phenylketonuria

Phenylketonuria (PKU) is the most common inborn error of amino acid metabolism and is characterized by mild to severe mental disability in untreated patients.


isolated Pierre-Robin syndrome

Pierre-Robin syndrome (or Pierre-Robin sequence) is characterized by triad of orofacial morphological anomalies consisting of retrognathism, glossoptosis and a posterior median velopalatal cleft.


isolated growth hormone deficiency type IA

An isolated growth hormone deficiency characterized by autosomal recessive inheritance of severe dwarfism with onset by 6 months of age and variable development of antibodies to growth hormone following exogenous supplementation that has material basis in null mutations in the GH1 gene on chromosome 17q23.3.


Laron syndrome

Laron syndrome is a congenital disorder characterized by marked short stature associated with normal or high serum growth hormone (GH) and low serum insulin-like growth factor-1 (IGF-I) levels which fail to rise after exogenous GH administration.


autosomal recessive polycystic kidney disease

An inherited disorder characterized by the development of cysts affecting the collecting ducts. It is frequently associated with hepatic involvement.


acquired polycythemia vera

Polycythemia vera (PV) is an acquired myeloproliferative disorder characterized by an elevated absolute red blood cell mass caused by uncontrolled red blood cell production, frequently associated with uncontrolled white blood cell and platelet production.


Chuvash polycythemia

Chuvash erythrocytosis is a rare, genetic, congenital secondary polycythemia disorder characterized by increased hemoglobin, hematocrit and erythropoietin serum levels and normal oxygen affinity, which usually manifests with headache, dizziness, dyspnea and/or plethora. Patients present an increased risk of hemorrhage, thrombosis and early death.


adult polyglucosan body disease

Adult polyglucosan body disease (APBD) is a glycogen storage disease of adults characterized by progressive upper and lower motor neuron dysfunction, progressive neurogenic bladder and cognitive difficulties that can lead to dementia.


Gitelman syndrome

Gitelman syndrome (GS), also referred to as familial hypokalemia-hypomagnesemia, is characterized by hypokalemic metabolic alkalosis in combination with significant hypomagnesemia and low urinary calcium excretion.


3MC syndrome 2

Any 3MC syndrome in which the cause of the disease is a mutation in the COLEC11 gene.


alveolar capillary dysplasia with misalignment of pulmonary veins

A rare and fatal developmental lung disease characterized by respiratory distress in neonates due to refractory hypoxemia and severe pulmonary arterial hypertension.


pulmonary venoocclusive disease

A disorder characterized by pulmonary venous constriction or occlusion, resulting in pulmonary hypertension.


pyruvate carboxylase deficiency disease

Pyruvate carboxylase (PC) deficiency is a rare neurometabolic disorder characterized by metabolic acidosis, failure to thrive, developmental delay, and recurrent seizures at an early age in severely affected patients.


pyruvate kinase deficiency of red cells

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


leukocyte adhesion deficiency type II

Leukocyte adhesion deficiency type II (LAD-II) is a form of LAD characterized by recurrent bacterial infections, severe growth delay and severe intellectual deficit.


inflammatory bowel disease 1

Any inflammatory bowel disease in which the cause of the disease is a mutation in the NOD2 gene.


respiratory distress syndrome in premature infants

Infant acute respiratory distress syndrome is a lung disorder that affects premature infants caused by developmental insufficiency of surfactant production and structural immaturity of the lungs. The symptoms usually appear shortly after birth and may include tachypnea, tachycardia, chest wall retractions (recession), expiratory grunting, nasal flaring and cyanosis during breathing efforts.


reticular dysgenesis

Reticular dysgenesis is the most severe form of severe combined immunodeficiency (SCID) and is characterized by bilateral sensorineural deafness and a lack of innate and adaptive immune functions leading to fatal septicemia within days after birth if not treated.


Revesz syndrome

Revesz syndrome is a rare severe phenotypic variant of dyskeratosis congenita (DC) with an onset in early childhood, characterized by features of DC (e.g. skin hyper/hypopigmentation, nail dystrophy, oral leukoplakia, high risk of bone marrow failure (BMF) and cancer, developmental delay sparse and fine hair) in conjunction with bilateral exudative retinopathy, and intracranial calcifications.


embryonal rhabdomyosarcoma

A poorly circumscribed morphologic variant of rhabdomyosarcoma. It is characterized by the presence of primitive skeletal muscle differentiation in any stage of myogenesis.


alveolar rhabdomyosarcoma

A rapidly growing malignant mesenchymal neoplasm. It is characterized by the presence of round cells with myoblastic differentiation and a fibrovascular stroma resembling an alveolar growth pattern. The tumor usually presents in the extremities.


Sandhoff disease

Sandhoff disease is a lysosomal storage disorder from the GM2 gangliosidosis family and is characterized by central nervous system degeneration.


Sjogren syndrome

An autoimmune disorder in which immune cells attack and destroy the glands that produce tears and saliva. Sjögren syndrome is also associated with rheumatic disorders such as rheumatoid arthritis or systemic lupus erythematosus. The hallmark symptoms of Sjögren syndrome are dry mouth and dry eyes. In addition, Sjogren syndrome may cause skin, nose, and vaginal dryness. It also may affect other organs of the body including the kidneys, blood vessels, lungs, liver, pancreas, and brain


Sjogren-Larsson syndrome

A neurocutaneous disorder caused by an inborn error of lipid metabolism and characterized by congenital ichthyosis, intellectual deficit, and spasticity.


Smith-Lemli-Opitz syndrome

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


spinal muscular atrophy, type IV

Proximal spinal muscular atrophy type 4 (SMA4) is the adult-onset form of proximal spinal muscular atrophy characterized by muscle weakness and hypotonia resulting from the degeneration and loss of the lower motor neurons in the spinal cord and the brain stem nuclei.


Canavan disease

A neurodegenerative disorder; its spectrum varies between severe forms with leukodystrophy, macrocephaly and severe developmental delay, and a very rare mild/juvenile form characterized by mild developmental delay.


Tay-Sachs disease

GM2 gangliosidosis, variant B or Tay-Sachs disease is marked by accumulation of G2 gangliosides due to hexosaminidase A deficiency.


testicular germ cell tumor

A germ cell tumor arising from the testis. Representative examples include teratoma, seminoma, embryonal carcinoma, and yolk sac tumor.


Dihydropyrimidine dehydrogenase (DPD) deficiency isaconditionin which the body cannot break down the nucleotides thymine and uracil. DPD deficiency can have a wide range of severity; some individuals may have various neurological problems, while others have no signsand symptoms. Signs and symptoms in severely affected individuals begin in infancy and may include seizures, intellectual disability, microcephaly, increased muscle tone (hypertonia), delayed motor skills, and autistic behavior. All individuals with the condition, regardless of the presence or severity of symptoms, are at risk for severe, toxic reactions to drugs called fluoropyrimidines which are used to treat cancer. Individuals with no symptoms may be diagnosed only by laboratory testing or after exposure to fluoropyrimidines. DPD deficiency is caused by mutations in the DPYD gene and is inherited in an autosomal recessive manner.


thyrotoxicosis

A hypermetabolic syndrome caused by the elevation of thyroid hormone levels in the serum. Signs and symptoms include tachycardia, palpitations, tremor, weight loss, warm weather intolerance, and moist skin. Causes include Graves disease, toxic nodular goiter, toxic thyroid nodule, and lymphocytic thyroiditis.


head and neck squamous cell carcinoma

A squamous cell carcinoma that arises from any of the following anatomic sites: lip and oral cavity, nasal cavity, paranasal sinuses, pharynx, larynx, and salivary glands.


mismatch repair cancer syndrome 1

A rare childhood cancer predisposition syndrome caused by biallelic inheritance of mutations in MLH1, MSH2, MSH6, or PMS2 genes. It is characterized by the development of childhood cancers, usually hematological malignancies and/or brain tumors, and colorectal cancers with multiple intestinal polyps. The majority of patients show signs of neurofibromatosis type 1.


congenital bilateral aplasia of vas deferens from CFTR mutation

An autosomal recessive disorder that is associated with mutation(s) in the CFTR gene, encoding cystic fibrosis transmembrane conductance regulator. Mutation(s) in the same gene are associated with cystic fibrosis.


von Willebrand disease 3

Type 3 von Willebrand disease (type 3 VWD) is the most severe form of VWD characterized by a bleeding disorder associated with a total or near-total absence of Willebrand factor (von Willebrand factor; VWF) in the plasma and cellular compartments, also leading to a profound deficiency of plasmatic factor VIII (FVIII).


Werner syndrome

A rare inherited syndrome characterized by premature aging with onset in the third decade of life and with cardinal clinical features including bilateral cataracts, short stature, graying and thinning of scalp hair, characteristic skin disorders and premature onset of additional age-related disorders.


Wernicke-Korsakoff syndrome

Wernicke-Korsakoff syndrome is a brain disorder, due to thiamine deficiency that has been associated with both Wernicke's encephalopathy and Korsakoff syndrome. The term refers to two different syndromes, each representing a different stage of the disease. Wernicke's encephalopathy represents the 'acute' phase and Korsakoff's syndrome represents the 'chronic' phase. However, they are used interchangeable in many sites. Wernicke's encephalopathy is characterized by confusion, abnormal stance and gait (ataxia), and abnormal eye movements (nystagmus). Korsakoff's syndrome is observed in a small number of patients. It is a type of dementia, characterized by memory loss and confabulation (filling in of memory gaps with data the patient can readily recall) and involvement of the heart, vascular, and nervous system. Wernicke-Korsakoff syndrome mainly results from chronic alcohol use, but also from dietary deficiencies, prolonged vomiting, eating disorders, systemic diseases (cancer, AIDS, infections), bariatric surgery, transplants, or the effects of chemotherapy. Studies indicate that there may be some genetic predisposition for the disease.Treatment involves supplementing the diet with thiamine. Wernicke encephalopathy is an acute syndrome and requires emergency treatment to prevent death and neurologic complications. In cases where the diagnosis is not confirmed, patients should still be treated while additional evaluations are completed.


Wilson disease

A very rare inherited multisystemic disease presenting non-specific neurological, hepatic, psychiatric or osseo-muscular manifestations due to excessive copper deposition in the body.


Coats disease

Coats disease (CD) is an idiopathic disorder characterized by retinal telangiectasia with deposition of intraretinal or subretinal exudates, potentially leading to retinal detachment and unilateral blindness. CD is classically an isolated and unilateral condition affecting otherwise healthy young children.


Lesch-Nyhan syndrome

Lesch-Nyhan syndrome (LNS) is the most severe form of hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency, a hereditary disorder of purine metabolism, and is associated with uric acid overproduction (UAO), neurological troubles, and behavioral problems.


Becker muscular dystrophy

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


T-B+ severe combined immunodeficiency due to gamma chain deficiency

Severe combined immunodeficiency (SCID) due to gamma chain deficiency, also called SCID-X1, is a form of SCID characterized by severe and recurrent infections, associated with diarrhea and failure to thrive.


autism, susceptibility to, X-linked 2

A class of genetic disorders resulting in intellectual disability that is associated either with mutations of genes located on the X chromosome or aberrations in the structure of the X chromosome (sex chromosome aberrations).


Allan-Herndon-Dudley syndrome

A syndrome with neuromuscular involvement characterized by infantile hypotonia, muscular hypoplasia, spastic paraparesis with dystonic/athetoic movements, and severe cognitive deficiency.


SHOX-related short stature

SHOX-related short stature is a primary bone dysplasia characterized by a height that is 2 standard deviations below the corresponding mean height for a given age, sex and population group, in the absence of obvious skeletal abnormalities and other diseases and with normal developmental milestones. Patients present normal bone age with normal limbs, shortening of the extremities (significantly lower extremities-trunk and sitting height-to-height ratios), normal hGH values, normal karyotype, and Leri-Weill dyschondrosteosis-like radiological signs (e.g. triangularization of distal radial epiphyses, pyramidalization of distal carpal row, and lucency of the distal radius on the ulnar side). Mesomelic disproportions and Madelung deformity are not apparent at a young age, but may develop later in life or never.


fragile X-associated tremor/ataxia syndrome

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a rare neurodegenerative disorder characterized by adult-onset progressive intention tremor and gait ataxia.


fragile X syndrome

A genetic syndrome caused by mutations in the FMR1 gene which is responsible for the expression of the fragile X mental retardation 1 protein. This protein participates in neural development. This syndrome is manifested with mental, emotional, behavioral, physical, and learning disabilities.


X-linked lymphoproliferative disease due to XIAP deficiency

A condition of decreased or absent presence of baculoviral IAP repeat-containing protein 4. Deficiency of this protein is associated with X-linked lymphoproliferative syndrome 2.


X-linked erythropoietic protoporphyria

X-linked form of erythropoietic protoporphyria.


Bruton-type agammaglobulinemia

X-linked agammaglobulinemia (XLA) is a clinically variable form of isolated agammaglobulinemia, an inherited immunodeficiency disorder, and is characterized in affected males by recurrent bacterial infections during infancy.


thrombophilia, X-linked, due to factor 9 defect

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


synovial sarcoma

Synovial sarcoma is an aggressive soft tissue sarcoma, occurring most commonly in adolescents and young adults (15 to 40 years), usually localized near the large joints of the extremities but also in the head and neck, mediastinum and viscera (lung, kidney etc), clinically presenting as a deep seated swelling or a painful mass often with an initial indolent course and is characterized by its local invasiveness and a propensity to metastasize. The origin of synovial sarcoma is likely from multipotent mesenchymal cells and not synovium (contrary to its name).


angioedema

Swelling involving the deep dermis, subcutaneous, or submucosal tissues, representing localized edema. Angioedema often occurs in the face, lips, tongue, and larynx.


Wiskott-Aldrich syndrome

Wiskott-Aldrich syndrome (WAS) is a primary immunodeficiency disease characterized by microthrombocytopenia, eczema, infections and an increased risk for autoimmune manifestations and malignancies.


X-linked Alport syndrome

X-linked form of Alport syndrome.


X-linked reticulate pigmentary disorder

X-linked reticulate pigmentary disorder is an extremely rare skin disease described in only four families to date and characterized in males by diffuse reticulate brown hyperpigmentated skin lesions developing in early childhood and a variety of systemic manifestations (recurrent pneumonia, corneal opacification, gastrointestinal inflammation, urethral stricture, failure to thrive, hypohidrosis, digital clubbing, and unruly hair and flared eyebrows), while in females, there is only cutaneous involvement with the development in early childhood of localized brown hyperpigmented skin lesions following the lines of Blaschko. This disease was first considered as a cutaneous amyloidosis, but amyloid deposits are an inconstant feature.


Fabry disease

Fabry disease (FD) is a progressive, inherited, multisystemic lysosomal storage disease characterized by specific neurological, cutaneous, renal, cardiovascular, cochleo-vestibular and cerebrovascular manifestations.


anosmia

Loss of or impaired ability to smell. This may be caused by olfactory nerve diseases; paranasal sinus diseases; viral respiratory tract infections; craniocerebral trauma; smoking; and other conditions.


Barth syndrome

Barth syndrome (BTHS) is an inborn error of phospholipid metabolism characterized by dilated cardiomyopathy (DCM), skeletal myopathy, neutropenia, growth delay and organic aciduria.


choroideremia

Choroideremia (CHM) is an X-linked chorioretinal dystrophy characterized by progressive degeneration of the choroid, retinal pigment epithelium (RPE) and retina.


red-green color blindness

Deuteranopia is a type of color vision deficiency where the green photoreceptors are absent. It affects hue discrimination in the same way as protanopia, but without the dimming effect. Like protanopia, it is hereditary, sex-linked, and found in about 1% of the male population.


occipital horn syndrome

Occipital horn syndrome (OHS) is a mild form of Menkes disease (MD), a syndrome characterized by progressive neurodegeneration and connective tissue disorders due to a copper transport defect.


deafness dystonia syndrome

An X-linked recessive neurodegenerative syndrome characterized by clinical manifestations commencing with early childhood onset hearing loss, followed by adolescent onset progressive dystonia or ataxia, visual impairment from early adulthood onwards and dementia from the 4th decade onwards.


Immunodysregulation - polyendocrinopathy - enteropathy - X-linked (IPEX) syndrome is a severe congenital systemic autoimmune disease characterized by refractory diarrhea, endocrinopathies, cutaneous involvement, and infections.


granulomatous disease, chronic, X-linked

An X-linked recessive form of chronic granulomatous disease caused by mutation(s) in the CYBB gene, encoding cytochrome b-245 beta chain.


hemophilia A

The most common form of hemophilia characterized by spontaneous or prolonged hemorrhages due to factor VIII deficiency.


hemophilia B

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


X-linked congenital generalized hypertrichosis is an extremely rare type of hypertrichosis lanuginosa congenita, a congenital skin disease, which is characterized by hair overgrowth on the entire body in males, and mild and asymmetric hair overgrowth in females. It is associated with a mild facial dysmorphism (anterverted nostrils, moderate prognathism), and, in a kindred, it was also associated with dental anomalies and deafness.


X-linked dominant hypophosphatemic rickets

X-linked hypophosphatemia (XLH) is a hereditary renal phosphate-wasting disorder characterized by hypophosphatemia, rickets and/or osteomalacia, and diminished growth.


hyper-IgM syndrome type 1

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


X-linked lymphoproliferative syndrome

X-linked lymphoproliferative disease is a hereditary immunodeficiency characterized, in the majority of cases, by an inadequate immune response to infection with the Epstein-Barr virus (EBV).


acute leukemia

A clonal (malignant) hematopoietic disorder with an acute onset, affecting the bone marrow and the peripheral blood. The malignant cells show minimal differentiation and are called blasts, either myeloid blasts (myeloblasts) or lymphoid blasts (lymphoblasts).


Menkes disease

A usually severe multisystemic disorder of copper metabolism, characterized by progressive neurodegeneration and marked connective tissue anomalies as well as typical sparse abnormal steely hair.


mucopolysaccharidosis type 2

A lysosomal storage disease leading to a massive accumulation of glycosaminoglycans and a wide variety of symptoms including distinctive coarse facial features, short stature, cardio-respiratory involvement and skeletal abnormalities. It manifests as a continuum varying from a severe to an attenuated form without neuronal involvement.


Duchenne muscular dystrophy

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


Ornithine transcarbamylase deficiency (OTCD) is a disorder of urea cycle metabolism and ammonia detoxification characterized by either a severe, neonatal-onset disease found almost exclusively in males, or later-onset (partial) forms of the disease. Both present with episodes of hyperammonemia that can be fatal and which can lead to neurological complications.


partial androgen insensitivity syndrome

Partial androgen insensitivity syndrome (PAIS) is a disorder of sex development (DSD) distinct from complete AIS (CAIS) characterized by the presence of abnormal genital development in a 46,XY individual with normal testis development and partial responsiveness to age-appropriate levels of androgens.


X-linked retinoschisis

A genetic ocular disease that is characterized by reduced visual acuity in males due to juvenile macular degeneration.


Rett syndrome

A severe neurodevelopmental disorder affecting the central nervous system.


Kennedy disease

Kennedy's disease, also known as bulbospinal muscular atrophy (BSMA), is a rare X-linked recessive motor neuron disease characterized by proximal and bulbar muscle wasting.


thrombocytopenia 1

An X-linked recessive bleeding disorder caused by mutation(s) in the WAS gene, encoding Wiskott-Aldrich syndrome protein, resulting in thrombocytopenia.


cyclic vomiting syndrome

A rare abnormality of the neuroendocrine system that is characterized by episodic nausea and vomiting.


maternally-inherited diabetes and deafness

Maternally inherited diabetes and deafness (MIDD) is a mitochondrial disorder characterized by maternally transmitted diabetes and sensorineural deafness.


Leber hereditary optic neuropathy

Leber's hereditary optic neuropathy (LHON) is a mitochondrial neurodegenerative disease affecting the optic nerve and often characterized by sudden vision loss in young adult carriers.


MELAS syndrome

MELAS (Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke) syndrome is a rare progressive multisystemic disorder characterized by encephalomyopathy, lactic acidosis, and stroke-like episodes. Other features include endocrinopathy, heart disease, diabetes, hearing loss, and neurological and psychiatric manifestations.


bladder exstrophy

Bladder exstrophy (or classic bladder exstrophy; CEB) is a congenital genitourinary malformation belonging to the spectrum of the exstrophy-epispadias complex (EEC) and is characterized by an evaginated bladder plate, epispadias and an anterior defect of the pelvis, pelvic floor and abdominal wall.


fatal familial insomnia

Fatal familial insomnia (FFI) is a very rare form of prion disease characterized by subacute onset of insomnia showing as a reduced overall sleep time, autonomic dysfunction, and motor disturbances.


benign prostatic hyperplasia

A non-cancerous nodular enlargement of the prostate gland. It is characterized by the presence of epithelial cell nodules, and stromal nodules containing fibrous and smooth muscle elements. It is the most common urologic disorder in men, causing blockage of urine flow.


childhood absence epilepsy

A familial generalized pediatric epilepsy, characterized by very frequent (multiple per day) absence seizures, usually occurring in children between the ages of 4 and 10 years, with, in most cases, a good prognosis.


primary hyperparathyroidism

Hyperfunction of the parathyroid glands resulting in the overproduction of parathyroid hormone. It is caused by parathyroid adenoma, parathyroid hyperplasia, parathyroid carcinoma, and multiple endocrine neoplasia. It is associated with hypercalcemia and hypophosphatemia. Signs and symptoms include weakness, fatigue, nausea, vomiting, constipation, depression, bone pain, osteoporosis, cystic bone lesions, and kidney stones.


Helicobacter pylori infection, susceptibility to


semantic dementia

Semantic dementia (SD) is a form of frontotemporal dementia (FTD), characterized by the progressive, amodal and profound loss of semantic knowledge (combination of visual associative agnosia, anomia, surface dyslexia or dysgraphia and disrupted comprehension of word meaning) and behavioral abnormalities, attributable to the degeneration of the anterior temporal lobes.


adenomyosis

The growth of endometrial tissue inside the muscular wall of the uterine corpus. Clinical manifestations include pain, dysmenorrhea, and menorrhagia.


maturity-onset diabetes of the young type 3

Monogenic diabetes caused by inactivating mutation(s) in the gene HNF1A, encoding hepatocyte nuclear factor 1-alpha.


prolactin-producing pituitary gland adenoma

Prolactinoma is a usually benign neoplasm of the pituitary gland that results in hyperprolactinemia. The most common clinical manifestations are amenorrhea and infertility in women; and impotence, decreased libido and infertility in men.


microtia

A congenital malformation of the external ear, seen more frequently in males, that occurs sporadically or is inherited, that is characterized by unilateral (79-93% of cases, 60% of which involve the right ear) or bilateral small and abnormally shaped auricles and that is often associated with atresia or stenosis of the ear canal, attention deficit disorders and delayed language development. The variation in auricle size ranges from grade I, where the auricle is simply smaller than normal, to grade IV, also known as anotia, where there is a complete absence of the external ear and of the auditory canal.


portal vein, cavernous transformation of


pleuropulmonary blastoma

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


cerebrovascular disorder

A disorder resulting from inadequate blood flow in the vessels that supply the brain. Representative examples include cerebrovascular ischemia, cerebral embolism, and cerebral infarction.


peroxisome biogenesis disorder 1B

An autosomal recessive condition caused by mutation(s) in the PEX1 gene, encoding peroxisome biogenesis factor 1. Peroxisome biogenesis disorder 1B is characterized by overlapping phenotypes of neonatal adrenoleukodystrophy and infantile Refsum disease.


bilineal acute myeloid leukemia

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


obesity disorder

A disorder involving an excessive amount of body fat.


progressive familial intrahepatic cholestasis type 2

Progressive familial intrahepatic cholestasis type 2 (PFIC2), a type of progressive familial intrahepatic cholestasis (PFIC), is a severe, neonatal, hereditary disorder in bile formation that is hepatocellular in origin and not associated with extrahepatic features. Initially, PFIC2 was reported under the name Byler syndrome.


intestinal hypomagnesemia 1

Primary hypomagnesemia with secondary hypocalcemia (PHSH) is a form of familial primary hypomagnesemia (FPH), characterized by severe hypomagnesemia and secondary hypocalcemia associated with neurological symptoms, including generalized seizures, tetany and muscle spasms. PHSH may be fatal or may result in chronic irreversible neurological complications.


torsion dystonia 7

A focal dystonia characterized by predominately cervical dystonia that has material basis in variation in the chromosome region 18p.


ethylmalonic encephalopathy

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


myotonic dystrophy type 2

Myotonic dystrophy type 2 (MD2), also known as proximal myotonic myopathy, is a very rare genetic multi-system disorder of late childhood or adult-onset characterized by mild myotonia, muscle weakness, and rarely cardiac conduction disorders.


astigmatism

Unequal curvature of the refractive surfaces of the eye. Thus a point source of light cannot be brought to a point focus on the retina but is spread over a more or less diffuse area. This results from the radius of curvature in one plane being longer or shorter than the radius at right angles to it. (Dorland, 27th ed)


dermatitis, atopic

Atopic dermatitis (AD) or atopic eczema is an itchy, inflammatory skin condition with a predilection for the skin flexures. It is characterized by poorly defined erythema with edema, vesicles, and weeping in the acute stage and skin thickening (lichenification) in the chronic stage.


spinocerebellar ataxia type 10

Spinocerebellar ataxia type 10 (SCA10) is a subtype of type I autosomal dominant cerebellar ataxia (ADCA type I). It is characterized by slowly progressive cerebellar syndrome and epilepsy, sometimes mild pyramidal signs, peripheral neuropathy and neuropsychological disturbances.


Omenn syndrome

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


ovarian germ cell tumor

A neoplasm that arises from the ovary and originates from germ cells. Representative examples include teratoma, embryonal carcinoma, yolk sac tumor, and dysgerminoma.


long QT syndrome 3

An autosomal dominant condition caused by mutation(s) in the SCN5A gene, encoding sodium channel protein type 5 subunit alpha. It is characterized by a prolonged QT interval that may result in torsade de pointes, ventricular fibrillation and/or sudden cardiac death.


sickle cell anemia

Sickle cell anemias are chronic hemolytic diseases that may induce three types of acute accidents: severe anemia, severe bacterial infections, and ischemic vasoocclusive accidents (VOA) caused by sickle-shaped red blood cells obstructing small blood vessels and capillaries. Many diverse complications can occur.


intervertebral disk degenerative disorder

Any disease of a degenerative nature that affects the intervertebral disk.


aceruloplasminemia

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


juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) is the term used to describe a group of inflammatory articular disorders of unknown cause that begin before the age of 16 and last over 6 weeks. The term juvenile idiopathic arthritis was chosen to signify the absence of any known mechanism underlying the disorder and to highlight the necessity of excluding other types of arthritis occurring in well defined diseases (in particular arthritis occurring in association with infectious, inflammatory and haematooncologic diseases).


acne

An inflammatory process of the sebaceous glands which is characterized by comedones, nodules, papules and/or pustules on the skin.


complex regional pain syndrome type 1

Complex regional pain syndrome type 1 (CRPS1) is a form of complex regional pain syndrome in which the pain is disproportionate to any known inciting event and is characterized by continuous pain, allodynia, or hyperalgesia as well as edema, coloration (changes in skin blood flow), or abnormal sudomotor activity in the region of pain. Onset of CRPS1 symptoms may occur within a few days to a month after an injury or trauma to the affected limb.


postural orthostatic tachycardia syndrome

A condition characterized by development of symptoms while standing. It is an autonomic nervous system disorder and the symptoms are relieved once the person sits back down. Symptoms include heart.


tricuspid atresia

Tricuspid atresia is (TA) a rare congenital heart malformation characterized by the congenital agenesis of tricuspid valve leading to severe hypoplasia of right ventricle (functionally univentricular). TA is associated with normally related or transposed great vessels (TGV), an obligatory interatrial connection that is crucial for survival (patent foramen ovale or atrial septal defect, osteum secondum type), ventricular septal defect (in 90% cases), pulmonary outflow obstruction - pulmonary atresia, stenosis or hypoplasia (usually in TA with normally related vessels but also in TGV), aortic coarctation and/or aortic arch interruption (usually in TA with TGV).


cerebral palsy, ataxic, autosomal recessive


propionic acidemia

Propionic acidemia (PA) is an organic aciduria caused by the deficient activity of the propionyl Coenzyme A carboxylase and is characterized by life threatening episodes of metabolic decompensation, neurological dysfunction and that may be complicated by cardiomyopathy.


pars planitis

An inflammatory disorder of the cilliary body in the uvea that affects healthy, younger individuals who are often asymptomatic. It has a long clinical course with relapses and remissions. Symptoms include mildly decreased vision and floaters. It may be associated with autoimmune disorders.


Phelan-McDermid syndrome

Monosomy 22q13 syndrome (deletion 22q13.3 syndrome or Phelan-McDermid syndrome) is a chromosome microdeletion syndrome characterized by neonatal hypotonia, global developmental delay, normal to accelerated growth, absent to severely delayed speech, and minor dysmorphic features.


alveolar soft part sarcoma

An alveolar soft part sarcoma occurring in adults. The most common site of involvement is the extremity, particularly the deep soft tissues of the thigh.


pathological gambling

A disorder characterized by a preoccupation with gambling and the excitement that gambling with increasing risk provides. Pathological gamblers are unable to cut back on their gambling, despite the fact that it may lead them to lie, steal, or lose a significant relationship, job, or educational opportunity.


hypotonia-cystinuria syndrome

A rare syndrome including neonatal and infantile hypotonia and failure to thrive, cystinuria type 1 and nephrolithiasis, growth retardation due to growth hormone deficiency, and minor facial dysmorphism.


lymphangioleiomyomatosis

A multifocal neoplasm with perivascular epithelioid cell differentiation affecting almost exclusively females of child-bearing age. It is characterized by the presence of smooth muscle and epithelioid cells and by the proliferation of lymphatic vessels. Sites of involvement include the lungs, mediastinum, and the retroperitoneum. It usually presents with chylous pleural effusion or ascites.


hyperinsulinism-hyperammonemia syndrome

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


gastrointestinal stromal tumor

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal (GI) tract, typically presenting in adults over the age of 40 (mean age 63), and only rarely in children, in various regions of the GI tract, most commonly the stomach or small intestine but also less commonly in the esophagus, appendix, rectum and colon. GISTs can be asymptomatic or present with various non-specific signs, depending on the location and size of tumor, such as loss of appetite, anemia, weight loss, fatigue, abdominal discomfort or fullness, nausea, vomiting, as well as an abdominal mass, blood in stool, and intestinal obstruction. GISTs can also be seen in familial syndromes such as Carney triad and neurofibromatosis type 1.


encephalopathy due to GLUT1 deficiency

Glucose transporter type 1 (GLUT1) deficiency syndrome is characterized by an encephalopathy marked by childhood epilepsy that is refractory to treatment, deceleration of cranial growth leading to microcephaly, psychomotor retardation, spasticity, ataxia, dysarthria and other paroxysmal neurological phenomena often occurring before meals. Symptoms appear between the age of 1 and 4 months, following a normal birth and gestation.


benign essential blepharospasm

Involuntary twitching of the eyelid.


fumaric aciduria

Fumaric aciduria (FA), an autosomal recessive metabolic disorder, is most often characterized by early onset but non-specific clinical signs: hypotonia, severe psychomotor impairment, convulsions, respiratory distress, feeding difficulties and frequent cerebral malformations, along with a distinctive facies. Some patients present with only moderate intellectual impairment.


Hurler syndrome

Hurler syndrome is the most severe form of mucopolysaccharidosis type 1 (MPS1), a rare lysosomal storage disease, characterized by skeletal abnormalities, cognitive impairment, heart disease, respiratory problems, enlarged liver and spleen, characteristic facies and reduced life expectancy.


Hurler-Scheie syndrome

Hurler-Scheie syndrome is the intermediate form of mucopolysaccharidosis type 1 (MPS1) between the two extremes Hurler syndrome and Scheie syndrome ; it is a rare lysosomal storage disease, characterized by skeletal deformities and a delay in motor development.


CINCA syndrome

Chronic Infantile Neurological, Cutaneous, and Articular (CINCA) syndrome is characterized by skin rash, joint involvement, chronic meningitis with granulocytes and, in some cases, sensorineural hearing loss and ocular signs.


angioid streaks

Small breaks in the elastin-filled tissue of the retina.


allergic rhinitis

Inflammation of the nasal mucous membranes caused by an IgE-mediated response to external allergens. The inflammation may also involve the mucous membranes of the sinuses, eyes, middle ear, and pharynx. Symptoms include sneezing, nasal congestion, rhinorrhea, and itching. It may lead to fatigue, drowsiness, and malaise thus causing impairment of the quality of life.


autosomal recessive limb-girdle muscular dystrophy type 2I

A subtype of autosomal recessive limb-girdle muscular dystrophy that presents a highly variable age of onset and phenotypic spectrum typically characterized by slowly progressive proximal weakness of the pelvic and shoulder girdle musculature (predominantly affecting the lower limbs), frequently associated with waddling gait, scapular winging, calf and tongue hypertrophy, exercise-induced myalgia, and myoglobinuria and/or elevated creatine kinase serum levels. Abdominal muscle weakness, cardiomyopathy, respiratory muscle involvement and various brain abnormalities have also been reported.


patent ductus arteriosus

A congenital defect characterized by the failure of the ductus arteriosus to close soon after birth. As a consequence, blood from the aorta mixes with blood from the pulmonary artery. If untreated, it may lead to congestive heart failure.


GRN-related frontotemporal lobar degeneration with Tdp43 inclusions

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


psoriatic arthritis

Joint inflammation associated with psoriasis.


Niemann-Pick disease type B

Niemann-Pick disease type B is a mild subtype of Niemann-Pick disease, an autosomal recessive lysosomal disease, and is characterized clinically by onset in childhood with hepatosplenomegaly, growth retardation, and lung disorders such as infections and dyspnea


juvenile myelomonocytic leukemia

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


Alzheimer disease 3

Alzheimer's disease with an early onset (starts before the age of 65). It is caused by mutations in the PSEN1 gene.


anxiety

Apprehension of danger and dread accompanied by restlessness, tension, tachycardia, and dyspnea unattached to a clearly identifiable stimulus.


tufted angioma

Tufted angioma is a very rare, benign, cutaneous, slow-growing, vascular tumor mostly developing in infancy or early childhood.


dermatofibrosarcoma protuberans

Dermatofibrosarcoma protuberans (DFSP) is a rare infiltrating soft tissue sarcoma, generally of low grade malignancy, arising from the dermis of the skin and characteristically associated with a specific chromosomal translocation t(17;22).


endometrial cancer

Primary or metastatic malignant neoplasm involving the endometrium (mucous membrane that lines the endometrial cavity).


ovarian hyperstimulation syndrome

A complication of ovulation induction in infertility treatment. It is graded by the severity of symptoms which include ovary enlargement, multiple ovarian follicles; ovarian cysts; ascites; and generalized edema. The full-blown syndrome may lead to renal failure, respiratory distress, and even death. Increased capillary permeability is caused by the vasoactive substances, such as vascular endothelial growth factors, secreted by the overly-stimulated ovaries.


leishmaniasis

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


chronic myelogenous leukemia, BCR-ABL1 positive

A chronic myeloproliferative neoplasm characterized by the expression of the BCR-ABL1 fusion gene. It presents with neutrophilic leukocytosis. It can appear at any age, but it mostly affects middle aged and older individuals. Patients usually present with fatigue, weight loss, anemia, night sweats, and splenomegaly. If untreated, it follows a biphasic or triphasic natural course; an initial indolent chronic phase which is followed by an accelerated phase, a blast phase, or both. Allogeneic stem cell transplantation and tyrosine kinase inhibitors delay disease progression and prolong overall survival.


specific phobia

An anxiety disorder characterized by an intense, irrational fear cued by the presence or anticipation of a specific object or situation. Exposure to the phobic stimulus immediately provokes an anxiety response. In adults, the specific phobia is recognized as excessive or unreasonable.


parathyroid gland carcinoma

A very rare, slow-growing, clinically serious endocrine tumor that generally develops in mid-adulthood. PRTC presents as a palpable painless mass in the neck and causes severe hypercalcemia and related symptoms, non-specific gastrointestinal manifestations, as well as renal and bone complications related to primary hyperparathyroidism (nephrolithiasis, impaired renal function, osteoporosis, bone pain, and pathologic fractures, etc.). Some PRTCs are however non-functioning tumors.


coronary artery disease, autosomal dominant, 1

Any coronary artery disease in which the cause of the disease is a mutation in the MEF2A gene.


endogenous depression

Depression which is considered strictly biological.


ichthyosis prematurity syndrome

Ichthyosis prematurity syndrome is a rare, syndromic congenital ichthyosis characterized by premature birth (at gestational weeks 30-32, in general) in addition to thick, caseous and desquamating epidermis, neonatal respiratory asphyxia, and persistent eosinophilia. After the perinatal period, a spontaneous improvement in the health of affected patients is observed and skin features (vernix caseosa-like scale) evolve into a mild presentation of flat follicular hyperkeratosis with atopy.


granulomatosis with polyangiitis

A small-vessel necrotizing vasculitis characterized by the association of inflammation of the vessel wall and peri- and extravascular granulomatosis.


growth delay due to insulin-like growth factor type 1 deficiency

Growth delay due to insulin-like growth factor I deficiency is characterized by the association of intrauterine and postnatal growth retardation with sensorineural deafness and intellectual deficit.


spinocerebellar ataxia type 8

Spinocerebellar ataxia type 8 (SCA8) is a subtype of type I autosomal dominant cerebellar ataxia (ADCA type I) characterized by cerebellar ataxia and cognitive dysfunction in almost three quarters of patients and pyramidal and sensory signs in approximately a third of patients.


choanal atresia

Choanal atresia (CA) is a congenital anomaly of the posterior nasal airway characterized by the obstruction of one (unilateral) or both (bilateral) choanal aperture(s), with clinical manifestations ranging from acute respiratory distress to chronic nasal obstruction.


mitochondrial trifunctional protein deficiency

Mitochondrial trifunctional protein (TFP) deficiency (TFPD) is a disorder of fatty acid oxidation characterized by a wide clinical spectrum ranging from severe neonatal manifestations including cardiomyopathy, hypoglycemia, metabolic acidosis, skeletal myopathy and neuropathy, liver disease and death to a mild phenotype with peripheral polyneuropathy, episodic rhabdomyolysis and pigmentary retinopathy..


long chain 3-hydroxyacyl-CoA dehydrogenase deficiency

Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) is a mitochondrial disorder of long chain fatty acid oxidation characterized in most patients by onset in infancy/ early childhood with hypoketotic hypoglycemia, metabolic acidosis, liver disease, hypotonia and frequently cardiac involvement with arrhythmias and/or cardiomyopathy.


idiopathic aplastic anemia

Aplastic anemia without a known cause.


AIDS

A syndrome resulting from the acquired deficiency of cellular immunity caused by the human immunodeficiency virus (HIV). It is characterized by the reduction of the Helper T-lymphocytes in the peripheral blood and the lymph nodes. Symptoms include generalized lymphadenopathy, fever, weight loss, and chronic diarrhea. Patients with AIDS are especially susceptible to opportunistic infections (usually pneumocystis carinii pneumonia, cytomegalovirus (CMV) infections, tuberculosis, candida infections, and cryptococcosis), and the development of malignant neoplasms (usually non-Hodgkin lymphoma and Kaposi sarcoma). The human immunodeficiency virus is transmitted through sexual contact, sharing of contaminated needles, or transfusion of contaminated blood.


lipomyelomeningocele

Lipomyelomeningocele is a rare neural tube closure defect characterized by a subcutaneous lipoma that extends through a defect in the lumbodorsal fascia, vertebral neural arch, and dura. This painless lesion can occur anywhere along the spinal canal but usually is found in the sacral or lumbar region. If left untreated it can cause tethered cord syndrome.


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.


obesity due to pro-opiomelanocortin deficiency

Pro-opiomelanocortin (POMC) deficiency is a form of monogenic obesity resulting in severe early-onset obesity, adrenal insufficiency, red hair and pale skin.


congenital primary aphakia

Congenital primary aphakia (CPA) is characterized by an absence of the lens. The prevalence is unknown. CPA can be associated with variable secondary ocular defects (including aplasia/dysplasia of the anterior segment of the eye, microphthalmia, and in some cases absence of the iris, retinal dysplasia, or sclerocornea). CPA results from early developmental arrest, around the 4th-5th week of embryogenesis, which prevents the formation of any lens structure. Mutations in the FOXE3 gene were identified in three affected siblings born to consanguineous parents.


preterm premature rupture of the membranes

A female reproductive system disease characterized by rupture of chorioamniotic membranes before 37 weeks of gestation.


herpes simplex encephalitis

Herpes simplex virus encephalitis (HSE) is caused by the infection of the central nervous system by Herpes simplex virus (HSV) that could have a devastating clinical course and a potentially fatal outcome particularly with delay or lack of treatment. HSV often involves the frontal and temporal lobes, usually asymmetrically, resulting in personality changes, cognitive impairment, aphasia, seizures, and focal weakness.


autoimmune pulmonary alveolar proteinosis

Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by the accumulation of a lipoproteinaceous substance in the distal air spaces which positively stains with periodic acid-Schiff (PAS).


Pitt-Hopkins syndrome

Pitt-Hopkins syndrome (PHS) is characterized by the association of intellectual deficit, characteristic facial dysmorphism and problems of abnormal and irregular breathing.


cholelithiasis

The presence of calculi in the gallbladder.


Leber congenital amaurosis 10

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


mucocutaneous lymph node syndrome

Kawasaki disease (KD) is a febrile, systemic, self-limiting vasculitis affecting children and characterized by inflammation in the medium sized vessels associated with coronary arterial aneurysms (CAA) that may be life threatening when untreated. KD is the most common cause of acquired heart disease in children in developed countries and is a risk factor for ischemic heart disease in adulthood.


proximal 16p11.2 microdeletion syndrome

A chromosomal anomaly characterized by developmental and language delays, mild intellectual disability, social impairments (autism spectrum disorders), mild variable dysmorphism and predisposition to obesity.


histiocytoma, Angiomatoid fibrous

A low malignant potential soft tissue neoplasm of uncertain differentiation. It typically affects young patients, presenting as a slowly growing nodular or cystic tumor mass, most often in the subcutaneous tissues of the extremities. Occasionally, patients have systemic symptoms (anemia, fever, and weight loss). This tumor has a relatively good prognosis. A minority of patients develop local recurrences. Metastases are rare.


Ewing sarcoma

A small round cell tumor that lacks morphologic, immunohistochemical, and electron microscopic evidence of neuroectodermal differentiation. It represents one of the two ends of the spectrum called Ewing sarcoma/peripheral neuroectodermal tumor. It affects mostly males under age 20, and it can occur in soft tissue or bone. Pain and the presence of a mass are the most common clinical symptoms.


diabetic ketoacidosis

The metabolic condition resulted from uncontrolled diabetes mellitus, in which the shift of acid-base status of the body toward the acid side because of loss of base or retention of acids other than carbonic acid is accompanied by the accumulation of ketone bodies in body tissues and fluids.


extraskeletal myxoid chondrosarcoma

A rare malignant soft tissue neoplasm of uncertain differentiation, characterized by the presence of chondroblast-like cells in a myxoid stroma and a multinodular growth pattern. The most common sites of involvement are the deep soft tissues of the extremities, particularly the thigh. It usually presents as an enlarging soft tissue mass. Patients may have long survivals, but local recurrences and metastases occur in approximately half of the cases. The most common site of metastasis is the lungs.


Crouzon syndrome-acanthosis nigricans syndrome

Crouzon syndrome with acanthosis nigricans (CAN) is a very rare, clinically heterogeneous form of faciocraniostenosis with Crouzon-like features and premature synostosis of cranial sutures (Crouzon disease), associated with acanthosis nigricans (AN).


acute promyelocytic leukemia

An aggressive form of acute myeloid leukemia (AML), characterized by arrest of leukocyte differentiation at the promyelocyte stage, due to a specific chromosomal translocation t(15;17) in myeloid cells. APL manifests with easy bruising, hemorrhagic diathesis and fatigue.


osteoarthritis susceptibility 5

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


congenital factor XI deficiency

Congenital factor XI deficiency is an inherited bleeding disorder characterized by reduced levels and activity of factor XI (FXI) resulting in moderate bleeding symptoms, usually occurring after trauma or surgery.


pseudohypoparathyroidism type 1C

A rare type of pseudohypoparathyroidism (PHP) characterized by resistance to parathyroid hormone (PTH) and other hormones, which manifests with hypocalcemia, hyperphosphatemia and elevated PTH levels, a constellation of clinical features collectively termed Albright's hereditary osteodystrophy (AHO), but normal activity of the stimulatory protein G (Gs alpha).


porphyria due to ALA dehydratase deficiency

Porphyria of doss or deficiency of delta-aminolevulinic acid dehydratase (DALAD) is an extremely rare form of acute hepatic porphyria characterized by neuro-visceral attacks without cutaneous manifestations.


sterile multifocal osteomyelitis with periostitis and pustulosis

An autoinflammatory disease caused by mutations in the IL1RN gene, which encodes the IL1 receptor antagonist. It presents in infancy, and is characterized by systemic inflammation, pustular rash, bone pain, sterile osteitis, and periostitis.


chronic thromboembolic pulmonary hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by the persistence of thromboemboli in the form of organized tissue obstructing the pulmonary arteries. The consequence is an increase in pulmonary vascular resistance (PVR) resulting in pulmonary hypertension (PH) and progressive right heart failure.


noise induced hearing loss

A condition in which a person loses the ability to hear due to exposure to high intensity sound.


hereditary antithrombin deficiency

A rare, genetic, hematological disease characterized by decreased levels of antithrombin activity in plasma resulting in impaired inactivation of thrombin and factor Xa. Patients have an increased risk for venous thromboembolism, usually in the deep veins of the arms, legs and pulmonary system and, on occasion, in other venous territories (e.g. cerebral veins or sinus, mesenteric, portal, hepatic, renal and/or retinal veins).


purine nucleoside phosphorylase deficiency

Purine nucleoside phosphorylase (PNP) deficiency is a disorder of purine metabolism characterized by progressive immunodeficiency leading to recurrent and opportunistic infections, autoimmunity and malignancy as well as neurologic manifestations.


trichotillomania

A disorder characterized by repetitive pulling out of one's hair resulting in noticeable hair loss; the individual experiences a rising subjective sense of tension before pulling out the hair and a sense of gratification or relief when pulling out the hair.


tuberous sclerosis 2

Tuberous sclerosis mapped to chromosome 16p13.3 (TSC2 gene).


metabolic dysfunction-associated steatotic liver disease

Metabolic dysfunction-associated steatotic liver disease (MASLD, formerly known as nonalcoholic fatty liver disease or NAFLD) is a type of liver disease that is not caused by alcohol. It typically does not cause symptoms in the early stages, but it can cause health problems due to fat accumulation, inflammation, and scarring in the liver.


congenital plasminogen activator inhibitor type 1 deficiency

Congenital plasminogen activator inhibitor type 1 (PAI-1) deficiency is a rare genetic bleeding disorder characterized by premature lysis of hemostatic clots and a moderate bleeding tendency.


myxoid liposarcoma

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


alpha 1-antitrypsin deficiency

Alpha-1-antitrypsin deficiency is a hereditary disease that develops in adulthood and is characterized by chronic liver disorders (cirrhosis), respiratory disorders (emphysema), and rarely panniculitis.


glycogen storage disease XV

Glycogen storage disease type 15 is an extremely rare genetic glycogen storage disease reported in one patient to date. Clinical signs included muscle weakness, cardiac arrhythmia associated with accumulation of abnormal storage material in the heart and glycogen depletion in skeletal muscle.


CBL-related disorder

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


primary hyperoxaluria type 3

Primary hyperoxaluria type 3 (PH3) is a disorder of glyoxylate metabolism that can be asymptomatic or characterized by oxalate nephrolithiasis.


Lipedema

Disorder of adipose tissue characterized by symmetric and bilateral enlargement of the lower extremities due to abnormal deposition of subcutaneous fat often in obese women. It is associated with hematoma, pain and may progress to secondary lymphedema which is known as lipolymphedema.


insomnia

A sleep disorder characterized by difficulty in falling asleep and/or remaining asleep.


psoriasis 14, pustular

Any psoriasis in which the cause of the disease is a mutation in the IL36RN gene.


Barrett esophagus

Esophageal lesion lined with columnar metaplastic epithelium which is flat or villiform. Barrett epithelium is characterized by two different types of cells: goblet cells and columnar cells. The symptomatology of Barrett esophagus is that of gastro-esophageal reflux. It is the precursor of most esophageal adenocarcinomas. (WHO)


pregnancy loss, recurrent, susceptibility to, 1

Any pregnancy loss, recurrent, susceptibility in which the cause of the disease is a mutation in the F5 gene.


graft versus host disease

An immune system disorder that occurs after allogeneic hematopoietic stem cell transplant and is a reaction of donor immune cells against host tissues. Activated donor T cells damage host epithelial cells after an inflammatory cascade that begins with the preparative regimen.


intracerebral hemorrhage

Bleeding into one or both cerebral hemispheres including the basal ganglia and the cerebral cortex. It is often associated with hypertension and craniocerebral trauma.


Idiopathic membranous glomerulonephritis (IMG) is a primary glomerular disease characterized by proteinuria, usually in the nephrotic range, with preserved renal function.


Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive (AR) disorder characterized by the formation and hyperexcretion of 2,8-dihydroxyadenine (2,8-DHA) in urine, causing urolithiasis and crystalline nephropathy.


C3 glomerulonephritis

Glomerulonephritis characterized by C3 accumulation with little or absent deposition of immunoglobulin, in the absence of ultrastructural electron-dense transformation seen in dense deposit disease.


retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome

A rare presumably genetic disorder characterized by idiopathic massive splenomegaly with pancytopenia and childhood-onset chronic optic nerve edema with slowly progressive vision loss. Additional reported features include anhidrosis, urticaria and headaches.


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


pulmonary hypertension, neonatal, susceptibility to


developmental and epileptic encephalopathy, 17

Any early infantile epileptic encephalopathy in which the cause of the disease is a mutation in the GNAO1 gene.


idiopathic CD4 lymphocytopenia

A rare primary immunodeficiency disorder characterized by persistent CD4 T-cell lymphopenia (less than 300 cells/B5L on multiple occasions) not associated with any other underlying primary or secondary immune deficiency. Patients typically present opportunistic infections (with cryptococcal, mycobacterial, candidal, varicella zoster virus infections and progressive multifocal leukoencephalopathy being the most prevalent), malignancies (mainly lymphoproliferative disorders), or autoimmune disorders. Some individuals are asymptomatic and incidentally diagnosed.


female infertility due to zona pellucida defect

Female infertility due to zona pellucida defect is a rare, genetic, female infertility disorder characterized by the presence of abnormal oocytes that lack a zona pellucida. Affected individuals are unable to conceive despite having normal menstrual cycles and sex hormone levels, as well as no obstructions in the fallopian tubes or defects of the uterus or adnexa.


ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder

An autosomal dominant non-syndromic intellectual disability that has material basis in an autosomal dominant mutation of ADNP on chromosome 20q13.13.


severe neurodegenerative syndrome with lipodystrophy


STING-associated vasculopathy with onset in infancy (SAVI) is a rare, genetic autoinflammatory disorder, type I interferonopathy due to constitutive STING (STimulator of INterferon Genes) activation, characterized by neonatal or infantile onset systemic inflammation and small vessel vasculopathy resulting in severe skin, pulmonary and joint lesions. Patients present with intermittent low-grade fever, recurrent cough and failure to thrive, in association with progressive interstitial lung disease, polyarthritis and violaceous scaling lesions on fingers, toes, nose, cheeks, and ears (which are exacerbated by cold exposure) that often progress to chronic acral ulceration, necrosis and autoamputation.


glucocorticoid resistance

An autosomal dominant condition due to mutation(s) in the NR3C1 gene, encoding the glucocorticoid receptor, resulting in decreased receptor affinity to glucocorticoids. Compensatory activation of the hypothalamic- pituitary-adrenal (HPA) axis results in increased mineralocorticoid and androgen production; clinical manifestations of glucocorticoid deficiency are rare.


autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency

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


achromatopsia 7

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


infantile-onset periodic fever-panniculitis-dermatosis syndrome

An autosomal recessive condition caused by mutation(s) in the OTULIN gene, encoding ubiquitin thioesterase otulin. It is characterized by neonatal onset of recurrent fever, erythematous rash with painful nodules, painful joints, and lipodystrophy.


myelodysplastic syndrome with excess blasts-1

A myelodysplastic syndrome defined by 5-9% blasts in the bone marrow, and <5% blasts in the blood. Approximately 25% of cases progress to an acute leukemia. (WHO)


myelodysplastic syndrome with excess blasts-2

A myelodysplastic syndrome defined by 10-19% blasts in the bone marrow or 5-19% blasts in the blood and <10% blasts in the bone marrow. Approximately 33% of cases progress to acute leukemia. The prognosis is usually poor. (WHO)


hereditary angioedema type 1

Hereditary angioedema type 1 (HAE 1) is a form of hereditary angioedema characterized by acute edema in subcutaneous tissues, viscera and/or the upper airway.


hereditary angioedema type 2

Hereditary angioedema type 2 (HAE 2) is a form of hereditary angioedema characterized by acute edema in subcutaneous tissues, viscera and/or the upper airway.


progressive non-fluent aphasia

Progressive non-fluent aphasia (PNFA) is a form of frontotemporal dementia (FTD), characterized by agrammatism, laborious speech, alexia, and agraphia, frequently accompanied by apraxia of speech (AOS). Language comprehension is relatively preserved.


gastric neuroendocrine tumor, well differentiated, low or intermediate grade

A well differentiated, low or intermediate grade tumor with neuroendocrine differentiation that arises from the stomach.


thyroid tumor

A benign or malignant neoplasm affecting the thyroid gland.


thyroid gland carcinoma

A carcinoma arising from the thyroid gland. It is usually an adenocarcinoma and includes the following main subtypes: follicular, papillary, medullary, poorly differentiated, and anaplastic.


porphyria cutanea tarda

The most common form of chronic hepatic porphyria. It is characterized by bullous photodermatitis.


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.


chronic primary adrenal insufficiency

A chronic disorder of the adrenal cortex resulting in the inadequate production of glucocorticoid and mineralocorticoid hormones.


constitutional neutropenia

A rare disorder characterized by recurrent infantile infections and absence of neutrophils in the peripheral blood.


acute myeloid leukemia with t(8;21)(q22;q22) translocation


autoimmune pancreatitis

Autoimmune pancreatitis (AIP) is a rare pancreatic disease characterized by chronic non-alcoholic pancreatitis that presents with abdominal pain, steatorrhea, obstructive jaundice and responds well to steroid therapy and is seen in two subforms: type 1 AIP which affects elderly males, involves other organs and has increased immunoglobin G4 (IgG4) levels and type 2 AIP which affects both sexes equally but presents at a younger age and has no other organ involvement or increased IgG4 levels.


short bowel syndrome

Short bowel syndrome is an intestinal failure due to either a congenital defect, intestinal infarction or extensive surgical resection of the intestinal tract that results in a functional small intestine of less than 200cm in length and is characterized by diarrhea, nutrient malabsoption, bowel dilation and dysmobility.


Bardet-Biedl syndrome

A ciliopathy with multisystem involvement. It is invariantly characterized by rod-cone dystrophy, and at least three additional non-ocular features such as intellectual disability, obesity, polydactyly, hypogonadism, or renal anomalies as primary manifestations. In the absence of one of these four primary clinical features, the diagnosis of BBS is made when at least two secondary features are observed, including hepatic fibrosis, diabetes mellitus, reproductive and developmental abnormalities, growth retardation, speech delays, or cardiovascular problems


Bartter syndrome

Bartter syndrome is a group of rare renal tubular disease characterized by impaired salt reabsorption in the thick ascending limb of Henle's loop and clinically by the association of hypokalemic alkalosis, hypercalciuria/nephrocalcinosis, increased levels of plasma renin and aldosterone, low blood pressure and vascular resistance to angiotensin II.


allergic bronchopulmonary aspergillosis

Allergic bronchopulmonary aspergillosis (ABPA) is a rare immunologic pulmonary disorder caused by hypersensitivity to Aspergillus fumigatus, clinically manifesting with poorly controlled asthma and recurrent pulmonary infiltrates.


opsoclonus-myoclonus syndrome

Opsoclonus myoclonus syndrome (OMS) is a rare neuroinflammatory disease of paraneoplastic, parainfectious or idiopathic origin, characterized by opsoclonus, myoclonus, ataxia, and behavioral and sleep disorders.


Diamond-Blackfan anemia

A congenital aregenerative and often macrocytic anemia with erythroblastopenia.


schistosomiasis

An infectious disease caused by parasitic trematodes of the genus Schistosoma that colonize human blood vessels and release eggs that can cause granulomatous reactions leading to acute (swimmer's itch or acute schistosomiasis syndrome) or chronic disease. Depending on where the eggs lodge, manifestations of chronic schistosomiasis can include diarrhea, abdominal pain, loss of appetite, anemia (intestines), hepatosplenism, periportal fibrosis with portal hypertension (liver), urogenital inflammation and scarring, hematuria and dysuria (genitourinary system). Other patients may be asymptomatic.


Brugada syndrome

A genetically heterogeneous condition characterized by complete or incomplete right bundle branch block accompanied by ST elevation in leads V1-V3. There is a high incidence of ventricular arrhythmia that may result in sudden death.


cryptogenic organizing pneumonia

Cryptogenic organizing pneumonia (COP) is a form of idiopathic interstitial pneumonia characterized pathologically by organizing pneumonia (OP) that presents with non-specific flu-like symptoms, as well as cough and dyspnea and where no etiological agent is found.


bronchiolitis obliterans syndrome

A lung disorder that is mainly associated with chronic allograft dysfunction after lung transplantation and that is characterized by inflammation and fibrosis of bronchiolar walls that reduce the diameter of the bronchioles and result in progressive and irreversible airflow obstruction.