Rubinstein-Taybi syndrome due to 16p13.3 microdeletion

Chromosome 16p13.3deletion syndrome is a chromosome abnormality that can affect many parts of the body. People with this condition are missing a small piece (deletion) of chromosome 16 at a location designated p13.3. Although once thought to be a severe form of Rubinstein-Taybi syndrome, it is now emerging as a unique syndrome. Signs and symptoms may include failure to thrive, hypotonia (reduced muscle tone), short stature, microcephaly (unusually small head), characteristic facial features, mild to moderate intellectual disability, organ anomalies (i.e. heart and/or kidney problems), and vulnerability to infections. Chromosome testing of both parents can provide information about whether the deletion was inherited. In most cases, parents do not have any chromosome abnormalities. However, sometimes one parent has a balanced translocation where a piece of a chromosome has broken off and attached to another one with no gain or loss of genetic material. The balanced translocation normally does not cause signs or symptoms, but it increases the risk for having a child with a chromosome abnormality like a deletion. Treatment is based on the signs and symptoms present in each person.To learn more about chromosome abnormalities in general, view our GARD fact sheet on Chromosome Disorders.


growth delay-hydrocephaly-lung hypoplasia syndrome

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Growth delay - hydrocephaly - lung hypoplasia, also named Game-Friedman-Paradice syndrome, is a rare developmental disorder described in 4 sibs so far and characterized by delayed fetal growth, hydrocephaly with patent aqueduct of Sylvius, underdeveloped lungs and various other anomalies such as small jaw, intestinal malrotation, omphalocele, shortness of lower limbs, bowed tibias and foot deformities.


age related macular degeneration 12

Any age-related macular degeneration in which the cause of the disease is a mutation in the CX3CR1 gene.


amelia of upper limb

A non-syndromic amelia that involves the forelimb.


autosomal recessive limb-girdle muscular dystrophy type 2O

Autosomal recessive limb-girdle muscular dystrophy type 2O (LGMD2O) is a form of limb-girdle muscular dystrophy characterized by an onset in childhood or adolescence of rapidly progressive proximal limb muscle weakness (particularly affecting the neck, hip girdle, and shoulder abductors), hypertrophy in the calves and quadriceps, ankle contractures, and myopia.


Boomerang dysplasia

Boomerang dysplasia (BD) is a rare lethal skeletal dysplasia characterized by severe short-limbed dwarfism, dislocated joints, club feet, distinctive facies and diagnostic x-ray findings of underossified and dysplastic long tubular bones, with a boomerang-like bowing.


disease arising from reactivation of latent virus

An infectious disease that arises from reactivation of a virus from a latent phase to a lytic phase.


nail tumor

A neoplasm involving a nail.


osteogenesis imperfecta type 6

Any osteogenesis imperfecta in which the cause of the disease is a mutation in the SERPINF1 gene.


AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndrome


leukoencephalopathy, diffuse hereditary, with spheroids 1

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


autosomal recessive progressive external ophthalmoplegia

Autosomal recessive form of progressive external ophthalmoplegia.


dysplasia of head of femur, Meyer type

Meyer dysplasia of the femoral head is a mild localized form of skeletal dysplasia characterized by delayed, irregular ossification of femoral capital epiphysis.


reproductive system neoplasm

A benign or malignant, primary or metastatic neoplasm affecting the male and female reproductive system.


mitochondrial complex I deficiency, nuclear type 1


sexual masochism disorder

A disorder characterized by recurrent sexual urges, fantasies, or behaviors involving the act (real, not simulated) of being humiliated, beaten, bound, or otherwise made to suffer.


autosomal recessive nonsyndromic hearing loss 6

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


benign neoplasm of pharynx

A benign neoplasm that involves the pharynx.


cone-rod dystrophy 2

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


hypomagnesemia, seizures, and intellectual disability 1


sporadic fatal insomnia

A rare sporadic human prion disease characterized by adult onset of progredient neurodegeneration presenting as a combination of psychiatric, sleep, and oculomotor disturbances, with development of progressive cognitive impairment (the predominantly affected cognitive domains being memory, temporal and/or spatial orientation, language, executive functions, and attention), postural instability, and sometimes additional motor abnormalities and autonomic hyperactivity, in the course of the disease. Bilateral thalamic hypometabolism on FDG-PET imaging and positive prion seeding activity in the cerebrospinal fluid are present in many cases. The disease is fatal within typically two to three years.


adult epithelioid sarcoma

An epithelioid sarcoma occurring in adults.


hemometra

Blood-filled uterus.


muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A13


spondyloepimetaphyseal dysplasia with multiple dislocations

A rare disorder caused by mutation in the KIF22 gene. It is characterized by short stature, midface retrusion, progressive knee malalignment, generalized ligamentous laxity, and mild spinal deformity.


congenital primary lymphedema of Gordon

A rare primary lymphedema characterized by bilateral, painless lower limb swelling present at birth. Prominent veins around the ankles and on the dorsa of the feet, dysplastic and upslanting toenails due to edema of the nailbed, and subtle dysmorphic facial features (such as high forehead, hypertelorism, depressed nasal bridge, mild bilateral ear dysplasia, and short neck) have also been described. The degree of lymphatic impairment is milder than in the otherwise clinically similar Milroy disease, as evidenced by slightly less severe lymphedema and significantly more uptake of tracers on lymphoscintigraphy.


hemochromatosis type 1

Hemochromatosis type 1 (classic) is the most common form of hereditary hemochromatosis (HH), a group of diseases characterized by excessive tissue iron deposition. Due to its incidence (1/200-1/1000), it is not considered as a rare disease, unlike the other subforms of the disease


platinum-induced ototoxicity

Progressive, bilateral, and irreversible sensorineural hearing loss as a frequently encountered side effect of platinum-based chemotherapy such as cisplatin and carboplatin.


spinal muscular atrophy with congenital bone fractures 1

Any prenatal-onset spinal muscular atrophy with congenital bone fractures in which the cause of the disease is a mutation in the TRIP4 gene.


Wells syndrome

Wells syndrome is characterized by the presence of recurrent cellulitis-like eruptions with eosinophilia.


vesiculobullous skin disease

Skin diseases characterized by local or general distributions of blisters. They are classified according to the site and mode of blister formation. Lesions can appear spontaneously or be precipitated by infection, trauma, or sunlight. Etiologies include immunologic and genetic factors. (From Scientific American Medicine, 1990)


femoral vein thrombophlebitis

A thrombophlebitis that involves the femoral vein.


intellectual disability, autosomal dominant 53


developmental and epileptic encephalopathy, 29

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


myopathy, autophagic vacuolar, infantile-onset


macular dystrophy, fenestrated sheen type


Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency is a hereditary disorder of purine metabolism associated with uric acid overproduction and a continuum spectrum of neurological manifestations depending on the degree of the enzyme deficiency.


terminal osseous dysplasia-pigmentary defects syndrome

A syndrome characterized by malformation of the hands and feet, pigmentary skin lesions on the face and scalp and digital fibromatosis.


ADan amyloidosis

A cerebral amyloid angiopathy characterized by ataxia, intention tremor, psychosis and dementia that has material basis in an autosomal dominant mutation of ITM2B on chromosome 13q14.2.


Charcot-Marie-Tooth disease, dominant intermediate A


hereditary spastic paraplegia 17

Any hereditary spastic paraplegia in which the cause of the disease is a mutation in the BSCL2 gene.


cobblestone lissencephaly without muscular or ocular involvement

Cobblestone lissencephaly without muscular or ocular involvement is a form of cobblestone lissencephaly characterized by a constellation of brain malformations which can either exist alone or in conjunction with minimal muscular and ocular abnormalities. The clinical features of the disease include severe developmental delay, increased head circumference, hydrocephalus and seizures.


clear cell meningioma

A WHO grade II morphologic variant of meningioma characterized by the presence of clear glycogen-rich polygonal cells.


migraine with brainstem aura

A migraine disorder characterized by episodes that are preceded by focal neurological symptoms originating in the brainstem.


primary ciliary dyskinesia 20

Any primary ciliary dyskinesia in which the cause of the disease is a mutation in the CCDC114 gene.


trisomy 8q

Trisomy 8q is a very rare disorder characterized by duplication of the long arm of chromosome 8. The most commonly associated abnormalities include low birth weight, craniofacial abnormalities (prominent forehead, flat occiput, hypertelorism, upslanting palpebral fissures, ear and nose deformities, thin upper lips), congenital heart defects, skeletal defects, psychomotor retardation. Phenotypic features vary in relation to the duplication size.


myasthenia, congenital, refractory to acetylcholinesterase inhibitors


basal ganglia calcification, idiopathic, 5


autosomal dominant Charcot-Marie-Tooth disease type 2 due to TFG mutation


mitochondrial complex 4 deficiency, nuclear type 20


Craniosynostosis-intracranial calcification is a form of syndromic craniosynostosis, characterized by pancraniosynostosis, head circumference below the mid-parental head circumference, mild facial dysmorphism (prominent supraorbital ridges, mild proptosis and maxillary hypoplasia) and calcification of the basal ganglia. The disease is associated with a favorable neurological outcome, normal intelligence and is inherited in an autosomal recessive manner.


autosomal dominant nonsyndromic hearing loss 49

An autosomal dominant nonsyndromic deafness that is characterized by moderate loss for low and mid frequencies and mild loss for high frequencies and has material basis in variation in the chromosome region 1q21-q23.


median nerve neuropathy

Disease involving the median nerve, from its origin at the brachial plexus to its termination in the hand. Clinical features include weakness of wrist and finger flexion, forearm pronation, thenar abduction, and loss of sensation over the lateral palm, first three fingers, and radial half of the ring finger. Common sites of injury include the elbow, where the nerve passes through the two heads of the pronator teres muscle (pronator syndrome) and in the carpal tunnel (carpal tunnel syndrome).


6q16 deletion syndrome

Deletion 6q16 syndrome is a Prader-Willi like syndrome characterized by obesity, hyperphagia, hypotonia, small hands and feet, eye/vision anomalies, and global developmental delay.


progressive myoclonic epilepsy type 6

Any progressive myoclonic epilepsy in which the cause of the disease is a mutation in the GOSR2 gene.


Charcot-Marie-Tooth disease type 2A2

Autosomal dominant Charcot-Marie-Tooth disease type 2A2 (CMT2A2) is a subtype of Autosomal dominant Charcot-Marie-Tooth disease type 2 characterized by the childhood onset of distal weakness and areflexia (with earlier and more severe involvement of the lower extremities), reduced sensory modalities (primarily pain and temperature sensation), foot deformities, postural tremor, scoliosis and contractures. Optic atrophy, vocal cord palsy with dysphonia, sensorineural hearing loss, spinal cord abnormalities and hydrocephalus have also been reported.


Adams-Oliver syndrome 6

Any Adams-Oliver syndrome in which the cause of the disease is a mutation in the DLL4 gene.


neurodevelopmental disorder with seizures, spasticity, and complete or partial agenesis of the corpus callosum


pacman dysplasia

Pacman dysplasia is characterized by epiphyseal stippling and osteoclastic overactivity. It has been described in less than 10 patients but may be underdiagnosed. It is characterized radiographically by severe stippling of the lower spine and long bones, and periosteal cloaking. Patients also have short metacarpals. The syndrome may be inherited as an autosomal recessive trait. This disorder should be included in the differential diagnosis of mucolipidosis type II. In order to make a definitive diagnosis, lysosomal storage should be investigated by electron microscopy, or enzyme assays should be performed. Familial recurrence can be easily detected by prenatal ultrasonography. This skeletal dysplasia is lethal.


Brucella abortus brucellosis

A bacterial infection caused by Brucella abortus that spreads from cattle to humans. Brucella abortus can cause of range of signs and symptoms including fever, chills, sweats, weight loss, malaise, headaches, myalgia, and arthralgia.


trisomy 5p

Trisomy 5p is a chromosomal abnormality resulting from the duplication of a segment of variable size of the short arm of chromosome 5, which usually involves the distal band 5p15. The clinical presentation is variable but is always associated with severe intellectual deficit.


cone-rod dystrophy 10

Any cone-rod dystrophy in which the cause of the disease is a mutation in the SEMA4A gene.


intellectual developmental disorder, autosomal recessive 67


furuncular myiasis due to Dermatobia hominis


Charcot-Marie-Tooth disease type 4E

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


hydrocephalus, nonsyndromic, autosomal recessive 1

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


MASS syndrome

A genetic disorder of connective tissue caused by mutations in the FBN1 gene. Connective tissue is the material between the cells of the body that gives tissues form and strength. Symptoms include mitral valve prolapse, nearsightedness, borderline and non-progressive aortic enlargement, and skin and skeletal findings that overlap with those seen in Marfan syndrome. Treatment is based on the individuals symptoms.


Alpha-N-acetylgalactosaminidase (NAGA) deficiency is a very rare lysosomal storage disease that is clinically and pathologically heterogeneous and is characterized by deficient NAGA activity.


familial hyperprolactinemia

Familial hyperprolactinemia is a rare, genetic endocrine disorder characterized by persistently high prolactin serum levels (not associated with gestation, puerperium, drug intake or pituitary tumor) in multiple affected family members. Clinically it manifests with signs usually observed in hyperprolactinemia, which are: secondary medroxyprogesterone acetate (MPA)-negative amenorrhea and galactorrhea in female patients, and hypogonadism and decreased testosterone level-driven sexual disfunction in male patients. Oligomenorrhea and primary infertility have also been reported in some female patients.


recessive dystrophic epidermolysis bullosa-generalized other

Recessive dystrophic epidermolysis bullosa (RDEB)-generalized other, also known as RDEB non-Hallopeau-Siemens type, is a subtype of DEB characterized by generalized cutaneous and mucosal blistering that is not associated with severe deformities.


Charcot-Marie-Tooth disease dominant intermediate E

Autosomal dominant intermediate Charcot-Marie-Tooth disease type E is characterized by the association of Charcot-Marie-Tooth disease (hereditary peripheral neuropathy) with nephropathy. So far, around 15 cases have been described. All patients had proteinuria (with or without microhematuria) at onset and some patients presented with nephrotic syndrome. In the majority of cases, pathological studies revealed glomerulosclerosis. The mode of transmission is unknown.


thiamine-responsive megaloblastic anemia syndrome

Thiamine-responsive megaloblastic anemia (TRMA) is characterized by a triad of megaloblastic anemia, non-type I diabetes mellitus, and sensorineural deafness.


oligoarticular juvenile idiopathic arthritis without anti-nuclear antibodies


mesomelia-synostoses syndrome

A syndromal osteochondrodysplasia due to a contiguous gene deletion syndrome, characterized by progressive bowing of forearms and forelegs leading to mesomelia, progressive intracarpal or intratarsal bone fusion and fusion of metacarpal bones with proximal phalanges, ptosis, hypertelorism, abnormal soft palate, congenital heart defect, and ureteral anomalies.


acquired idiopathic torsion dystonia

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


familial idiopathic dilatation of the right atrium

Idiopathic dilatation of the right atrium (IDRA) is a rare congenital heart malformation of unknown etiology that is characterized by an extremely dilated right atrium, and that is usually asymptomatic and fortuitously discovered by echocardiography or chest radiography, and can be sometimes associated with other anomalies such as atrial arrhythmias (e.g. atrial flutter, atrial fibrillation, supraventricular tachycardia), severe tricuspid regurgitation, or atrial thrombus that could lead to potentially life-threatening thromboembolic complications.


intellectual disability, autosomal dominant 8

Any autosomal dominant non-syndromic intellectual disability in which the cause of the disease is a mutation in the GRIN1 gene.


isolated microphthalmia

A microphthalmia that is not part of a larger syndrome.


childhood-onset nemaline myopathy

Childhood onset nemaline myopathy, or mild nemaline myopathy is a type of nemaline myopathy (NM) characterized by distal muscle weakness, and sometimes slowness of muscle contraction.


lymph node cancer

A primary or metastatic malignant tumor involving the lymph node. Lymphomas and metastatic carcinomas are representative examples. -- 2004


familial partial lipodystrophy, Dunnigan type

Familial Partial lipodystrophy, Dunnigan type (FPLD2) is a rare form of genetic lipodystrophy characterized by a loss of subcutaneous adipose tissue from the trunk, buttocks and limbs; fat accumulation in the neck, face, axillary and pelvic regions; muscular hypertrophy; and usually associated with metabolic complications such as insulin resistance, diabetes mellitus, dyslipidemia and liver steatosis.


glycogen storage disease due to muscle and heart glycogen synthase deficiency

A glycogen storage disease characterized by muscle and heart glycogen deficiency. It has been described in three siblings (two brothers and their younger sister). The older brother died at 10.5 years of age as a result of sudden cardiac arrest and the younger brother presented with hypertrophic cardiomyopathy, abnormal heart rate and blood pressure during exercise, and muscle fatigability. The sister showed no symptoms but a lack of glycogen was identified through muscle biopsy. The syndrome is caused by homozygous missense mutations in the gene encoding muscle glycogen synthase.


malignant lymphatic vessel tumor

Neoplasms composed of lymphoid tissue, a lattice work of reticular tissue the interspaces of which contain lymphocytes. The concept does not refer to neoplasms located in lymphatic vessels.


pressure-induced localized lipoatrophy

Pressure-induced localized lipoatrophy is a rare, acquired, localized lipodystrophy characterized by band-like, horizontal, asymptomatic, lipoatrophic depressions with clinically normal overlying skin usually involving the anterolateral aspect of the thighs. An identifiable history of the repeated mechanical microtrauma due to occupational or postural habits is present.


Anophthalmia-esophageal atresia syndrome belongs to the group of syndromic microphthalmias and is characterized by the association of uni- or bilateral anophthalmia or microphthalmia, and esophageal atresia with or without trachoesophageal fistula.


Leber congenital amaurosis 1

Any Leber congenital amaurosis in which the cause of the disease is a mutation in the GUCY2D gene.


immunodeficiency 99 with hypogammaglobulinemia and autoimmune cytopenias

An autosomal recessive immunologic disorder characterized by the onset of recurrent sinopulmonary infections in early childhood. Laboratory studies reveal hypogammaglobulinemia with decreased memory B cells that show impaired class-switch recombination (CSR) and decreased somatic hypermutation (SHM). Due to abnormal antibody production and impaired self-tolerance, patients may develop autoimmune cytopenias, such as thrombocytopenia, or autoimmune features, such as vitiligo. There are also defects in the T-cell compartment.


alternating hemiplegia of childhood 1

Any alternating hemiplegia of childhood in which the cause of the disease is a mutation in the ATP1A2 gene.


partial deletion of the short arm of chromosome 8

Chromosome 8p deletion is a chromosome abnormality that affects many different parts of the body. People with this condition are missing genetic material located on the short arm (p) of chromosome 8 in each cell. The severity of the condition and the associated signs and symptoms vary based on the size and location of the deletion and which genes are involved. Most cases are not inherited, although affected people can pass the deletion on to their children. Treatment is based on the signs and symptoms present in each person.


heart-hand syndrome

Heart-hand syndrome refers to a group of congenital disorders characterized by malformations of the upper limbs and heart. To date, heart-hand syndrome comprises the following rare syndromes; Holt-Oram syndrome; heart-hand syndrome type 2; heart-hand syndrome type 3; heart hand syndrome, Slovenian type, brachydactyly-long thumb; and patent ductus arteriosus-bicuspid aortic valve - hand anomalies.


chikungunya

An infection that is caused by the Chikungunya virus, which is transmitted by mosquitoes; it is characterized by fever and severe arthralgia.


posttransplant acute limbic encephalitis

Posttransplant acute limbic encephalitis is a rare, acquired, non-paraneoplastic limbic encephalitis disorder, that develops in the setting of treatment-related immunosuppression, typically after allogeneic hemapoietic stem cell transplantation, characterized by onset of confusion, headache, anterograde amnesia, seizures and/or loss of consciousness 2-6 weeks following transplantation. Bilateral, non-enhancing T2 hyperintensities in limbic structures are observed on magnetic resonance imaging. Mild cerebrospinal fluid pleocytosis and syndrome of inappropriate antidiuretic hormone secretion may also be associated.


perioral myoclonia with absences

Perioral myoclonia with absences is a rare epilepsy syndrome characterized by absence seizures with perioral myoclonia as the main seizure type, accompanied by generalized tonic-clonic seizures, appearing before or together with absences. Consciousness is usually impaired, although to variable degree. Commonly observed absence status epilepticus, poor response to antiepileptic drugs and persistence of seizures into adulthood, in the presence of normal neurological status and intelligence, are additional clinical features of this syndrome.


factor VII and Factor VIII, combined deficiency of


X-linked cerebral-cerebellar-coloboma syndrome syndrome

A rare, genetic syndrome with a cerebellar malformation as major feature characterized by cerebellar vermis hypo- or aplasia, ventriculomegaly, agenesis of corpus callosum and abnormalities of the brainstem and cerebral cortex in association with ocular coloboma. Clinically, patients show hydrocephalus at birth, neonatal hypotonia with abnormal breathing pattern, ocular abnormalities with impaired vision, severe psychomotor delay, and seizures.


neurodevelopmental disorder with dysmorphic facies and skeletal and brain abnormalities


anterior foramen magnum meningioma

A meningioma that affects the anterior foramen magnum.


white platelet syndrome

White platelet syndrome (WPS) is is a platelet granule disorder characterized by thrombocytopenia, increased mean platelet volumes, decreased platelet responsiveness to aggregating agents, and significant defects in platelet ultrastructural morphology leading to prolonged bleeding times and bleeding.


neuronal ceroid lipofuscinosis 9

Neuronal ceroid lipofuscinosis 9 (CLN9-NCL) is a rare condition that affects the nervous system. Signs and symptoms of the condition generally develop in early childhood (average age 4 years) and may include loss of muscle coordination (ataxia), seizures that do not respond to medications, muscle twitches (myoclonus), visual impairment, and developmental regression (the loss of previously acquired skills). The underlying genetic cause of CLN9-NCLis unknown but it appears to be inherited in an autosomal recessive manner. Treatment options are limited to therapies that can help relieve some of the symptoms.


Charcot-Marie-Tooth disease, demyelinating, type 1J


Becker nevus syndrome

Becker nevus syndrome is characterized by the presence of a Becker nevus in association withunderdevelopment (hypoplasia)of the breast or other skin-related, muscular, or skeletal defects, all of which usually involve the same side of the bodyas the nevus (ipsilateral). Specific signs and symptoms in addition to the nevus may include ipsilateral breast hypoplasia;skeletal abnormalities such ashypoplasia of the shoulder girdle, scoliosis, fused ribs, and ipsilateral shortness of the arm; and several other features. Thecondition is thought to be sporadic (occurring in individuals with no history of the condition in the family). Treatment varies depending upon the specific symptoms present and the extent of the condition in the affected individual.


cutaneous mucinosis

The mucinoses are a diverse group of disorders which have in common the deposition of basophilic, finely granular and stringy material (mucin) in the connective tissues of the dermis (dermal mucinoses), in the pilosebaceous follicles (follicular mucinoses), or in the epidermis and tumors derived therefrom (epithelial mucinoses).


X-linked non progressive cerebellar ataxia is a rare hereditary ataxia characterized by delayed early motor development, severe neonatal hypotonia, non-progressive ataxia and slow eye movements, presenting normal cognitive abilities and absence of pyramidal signs. Frequently patients also manifest intention tremor, mild dysphagia, and dysarthria. Brain MRI reveals global cerebellar atrophy with absence of other malformations or degenerations of the central and peripheral nervous systems.


Curly hair - acral keratoderma - caries syndrome

Curly hair-acral keratoderma-caries syndrome is an extremely rare ectodermal dysplasia syndrome characterized by premature loss of curly, brittle, dry hair, premature loss of teeth due to caries, nail dystrophy with thickening of the finger- and toe-nails, acral keratoderma and hypohidrosis. Additionally, sparse eyebrows and eyelashes, receding frontal hairline and flattened malar region are associated. The severity of features appears to increase with age.


pseudohypoaldosteronism type 2E

Any pseudohypoaldosteronism type 2 in which the cause of the disease is a mutation in the CUL3 gene.


HAND1 related congenital heart defect

A heart disease that is present at birth caused by a variation in HAND1. Representative examples include ventricular septal defect, tetralogy of Fallot, and double outlet right ventricle.


pustular pyoderma gangrenosum

A rare subtype of pyoderma gangrenosum characterized by multiple painful, sterile pustules with a surrounding erythematous halo, predominantly occurring on the trunk and extensor surfaces of the limbs, and potentially persisting for months. Histopathology shows a dermal neutrophilic infiltrate and subcorneal neutrophilic micropustules. The condition is commonly associated with inflammatory bowel disease.


Meckel syndrome, type 2

Any Meckel syndrome in which the cause of the disease is a mutation in the TMEM216 gene.


fundus dystrophy, pseudoinflammatory, recessive form


A neoplasm of lymphoblasts committed to the T-cell lineage, typically composed of small to medium-sized blast cells. When the neoplasm involves predominantly the bone marrow and the peripheral blood, it is called T acute lymphoblastic leukemia. When it involves nodal or extranodal sites it is called T lymphoblastic lymphoma. (WHO, 2001)


immunodeficiency, common variable, 5

Any common variable immunodeficiency in which the cause of the disease is a mutation in the MS4A1 gene.


autosomal recessive nonsyndromic hearing loss 2

Any autosomal recessive nonsyndromic deafness in which the cause of the disease is a mutation in the MYO7A gene.


isolated total cerebellar vermis agenesis


neurodevelopmental disorder with short stature, prominent forehead, and feeding difficulties


hemophilic arthropathy

A form of arthritis that affects hemophiliacs, which is characterized by bleeding into the joint space.


sacral hemangiomas multiple congenital abnormalities


hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1

This is an autosomal dominant disorder caused by mutations in the RUNX1 gene and is characterized by mild to moderate thrombocytopenia, platelet functional and/or ultrastructural defects and a predisposition to hematologic malignancies, most often AML and MDS, and less frequently T-ALL.


striate palmoplantar keratoderma

Striate palmoplantar keratoderma is an isolated, focal, hereditary palmoplantar keratoderma characterized by linear hyperkeratosis along the flexor aspect of the fingers and on palms, as well as focal hyperkeratosis of the plantar skin. Patients present with painful thickening of the skin on palms and soles, with occasional fissuring, blistering and hyperhidrosis. Rarely, hyperkeratosis on other areas may be seen (knees, dorsal aspects of the digits). Histopatologically, widened intercellular spaces between keratinocytes are observed.


muscular dystrophy-dystroglycanopathy type B5

A congenital muscular dystrophy characterized by autosomal recessive inheritance of muscular dystrophy with variable penetrance of intellectual disability and structural brain abnormalities that has material basis in homozygous or compound heterozygous mutation in the FKRP gene on chromosome 19q13.3.


familial primary hypomagnesemia with normocalciuria and normocalcemia

Familial primary hypomagnesemia with normocalciuria and normocalcemia (FPHNN) is a form of familial primary hypomagnesemia (FPH), characterized by low serum magnesium (Mg) values but inappropriate normal urinary Mg values (i.e. renal hypomagnesemia). The typical symptoms are weakness of the limbs, vertigo, headaches, seizures, brisk tendon reflexes and mild to moderate psychomotor delay.


Acute post streptococcal glomerulonephritis is an immunologic response of the kidney to infection, characterized by the sudden appearance of edema, hematuria, proteinuria and hypertension. It is essentially a disease of childhood that accounts for approximately 90% of renal disorders in children. The disease occurs especially in children between the ages of 2 and 12 years and young adults, and more often in male than in female.


autosomal dominant complex spastic paraplegia

Autosomal dominant form of complex hereditary spastic paraplegia.


disorder of phospholipids, sphingolipids and fatty acids biosynthesis


syndromic X-linked intellectual disability 7

Syndromic X-linked intellectual disability 7, also called MRXS7, is characterized by X-linked intellectual deficit, obesity, hypogonadism, and tapering fingers.


Charcot-Marie-Tooth disease type 4J

Charcot-Marie-Tooth disease, type 4J (CMT4J) belongs to the genetically heterogeneous group of CMT peripheral sensorimotor polyneuropathy diseases.


Brugada syndrome 2

Any Brugada syndrome in which the cause of the disease is a mutation in the GPD1L gene.


STAT3-related early-onset multisystem autoimmune disease

An autosomal dominant condition caused by mutation(s) in the STAT3 gene, encoding signal transducer and activator of transcription 3. It is characterized by variable features along a spectrum of autoimmune disorders affecting multiple organs. Common manifestations may include insulin-dependent diabetes mellitus and autoimmune enteropathy, or celiac disease, and autoimmune hematologic disorders. Other features include short stature and nonspecific dermatitis.


autosomal recessive nonsyndromic hearing loss 15

Any autosomal recessive nonsyndromic deafness in which the cause of the disease is a mutation in the GIPC3 gene.


candidiasis, familial, 6

Any familial chronic mucocutaneous candidiasis in which the cause of the disease is a mutation in the IL17F gene.


pseudohypoaldosteronism type 2B

Any pseudohypoaldosteronism type 2 in which the cause of the disease is a mutation in the WNK4 gene.


primary brain neoplasm

A neoplasm arising from the brain.


hereditary hemorrhagic telangiectasia

A disorder of angiogenesis leading to arteriovenous dilatations: cutaneo-mucosal hemorrhagic telangiectasias and visceral shunting.


metachronous osteosarcoma of the bone

A bone osteosarcoma that has metastasized to skeletal or extraskeletal sites.


neurodevelopmental disorder with hypotonia, seizures, and absent language


intestinal botulism

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


benign partial epilepsy with secondarily generalized seizures in infancy

Benign partial epilepsy with secondarily generalized seizures in infancy is a rare infantile epilepsy syndrome characterized by seizures presenting with motion arrest and staring. They are followed by generalized tonic-clonic convulsions with normal interictal EEG and focal paroxysmal discharges, followed by generalization in ictal EEG. Seizures usually occur in clusters and are responsive to treatment. Psychomotor development is normal.


isolated adrenal insufficiency

An ABCD1 deficiency that presents with primary adrenocortical insufficiency between age two years and adulthood and most commonly by age 7.5 years, without evidence of neurologic abnormality; however, some degree of neurologic disability (most commonly adrenomyeloneuropathy (AMN)) usually develops by middle age.


secondary dentine

Dentin formed by normal pulp after completion of root end formation.


Castleman-Kojima disease

A clinicopathologic variant of multicentric Castleman's disease characterized by thrombocytopenia, ascites (anasarca), microcytic anemia, myelofibrosis, renal dysfunction, and organomegaly


brittle cornea syndrome

Brittle cornea syndrome is a form of Ehlers-Danlos syndrome characterized by a severe ocular manifestations due to extreme corneal thinning and fragility with rupture in the absence of significant trauma, and progression to blindness. Extraocular manifestations comprise deafness, developmental hip dysplasia, and joint hypermobility.


thanatophoric dysplasia type 1

Thanatophoric dysplasia type 1 (TD1) is a form of TD characterized by short, bowed femurs, micromelia, narrow thorax, and brachydactyly.


Pierpont syndrome

Pierpont syndrome is a rare subcutaneous tissue disorder characterized by axial hypotonia after birth, prolonged feeding difficulties, moderate to severe global developmental delay, seizures (in particular absence seizures), fetal digital pads, distinctive plantar fat pads anteromedial to the heels, deep palmar and plantar grooves. Additionally, distinct craniofacial dysmorphic features, notably a broad face with high forehead, high anterior hairline, narrow palpebral fissures that take on a crescent moon shape when smiling, broad nasal bridge and tip with anteverted nostrils, mild midfacial hypoplasia, long, smooth philtrum, thin upper lip vermillion, small, widely spaced teeth and flat occiput/microcephaly/brachycephaly, are also chararteristic. Over time, fat pads may become less prominent and disappear.


immature cataract

A cataract disease in which the cataract contains some transparent protein


hereditary spastic paraplegia 62

Autosomal recessive spastic paraplegia type 62 is a pure or complex form of hereditary spastic paraplegia characterized by an onset in the first decade of life of spastic paraperesis (more prominent in lower than upper extremities) and unsteady gait, as well as increased deep tendon reflexes, amyotrophy, cerebellar ataxia, and flexion contractures of the knees, in some.


myasthenic syndrome, congenital, 25, presynaptic


hypoplastic left heart syndrome 2

Any hypoplastic left heart syndrome in which the cause of the disease is a mutation in the NKX2-5 gene.


congenital bowing of long bones

Long bone bowing is a congenital condition described by the presence of symmetric or asymmetric angular deformity and shortening of the long bones, particularly the femurs, tibiae and ulnae.


hyperargininemia

Arginase deficiency is a rare autosomal recessive amino acid metabolism disorder characterized clinically by variable degrees of hyperammonemia, developing from about 3 years of age, and leading to progressive loss of developmental milestones and spasticity in the absence of treatment.


congenital stationary night blindness 1C

Any congenital stationary night blindness in which the cause of the disease is a mutation in the TRPM1 gene.


autosomal recessive nonsyndromic hearing loss 22

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


syndromic X-linked intellectual disability 34

Macrocephaly-intellectual disability-left ventricular non compaction syndrome is a rare, genetic, syndromic intellectual disability characterized by motor and cognitive developmental delay with language impairment, macrocephaly, hypotonia, dysmorphic facial features (including long face, slanting palpebral fissures and prominent, flattened nose) and left ventricular noncompaction cardiomyopathy. Patients also present skeletal abnormalities (e.g. scoliosis, finger clinodactyly, pes planus), slender build and shy behavior. Strabismus and various neurological signs (including ataxia, tremor and hyperreflexia) may be associated, as well as epilepsy, autism and MRI findings showing a small cerebellum and abnormalities of the corpus callosum. A phenotypic variant with no cardiac involvement has been reported.


RAB23-related Carpenter syndrome

Any Carpenter syndrome in which the cause of the disease is a mutation in the RAB23 gene.


hereditary spastic paraplegia 19

Autosomal dominant spastic paraplegia type 19 is a pure form of hereditary spastic paraplegia characterized by a slowly progressive and relatively benign spastic paraplegia presenting in adulthood with spastic gait, lower limb hyperreflexia, extensor plantar responses, bladder dysfunction (urinary urgency and/or incontinence), and mild sensory and motor peripheral neuropathy.


central precocious puberty

Central precocious puberty (CPP), also referred to as gonadotropin dependent precocious puberty, is an endocrine-related developmental disease characterized by the onset of pubertal changes, with development of secondary sexual characteristics and accelerated growth and bone maturation, before the normal age of puberty (8 years in girls and 9 years in boys).


dyskeratosis congenita, autosomal dominant 1

A dyskeratosis congenita that has material basis in an autosomal dominant mutation of TERC on chromosome 3q26.2.


endocardium disorder

A disease involving the endocardium.


lichen disease

A long-term skin condition that mainly affects the skin of the genitals. It usually causes itching and white patches to appear on the affected skin.


anaplastic/large cell medulloblastoma

A medulloblastoma composed of sheets of large cells mixed with cells characterized by marked nuclear pleomorphism and high mitotic activity.


familial glucocorticoid deficiency

Familial glucocorticoid deficiency (FGD) is a group of primary adrenal insufficiencies characterized clinically by neonatal hyperpigmentation, hypoglycemia, failure to thrive, and recurrent infections, and biochemically by glucocorticoid deficiency without mineralocorticoid deficiency.


intracranial hypotension

Reduction of cerebrospinal fluid pressure characterized clinically by headache which is maximal in an upright posture and occasionally by an abducens nerve palsy (see abducens nerve diseases), neck stiffness, hearing loss (see deafness); nausea; and other symptoms. This condition may be spontaneous or secondary to spinal puncture; neurosurgical procedures; dehydration; uremia; trauma (see also craniocerebral trauma); and other processes. Chronic hypotension may be associated with subdural hematomas (see hematoma, subdural) or hygromas. (From Semin Neurol 1996 Mar;16(1):5-10; Adams et al., Principles of Neurology, 6th ed, pp637-8)


pseudohypoaldosteronism, type IB2, autosomal recessive


infantile epilepsy syndrome

An epilepsy syndrome that occurs between 28 days to one year of life.


exudative vitreoretinopathy 6

Any exudative vitreoretinopathy in which the cause of the disease is a mutation in the ZNF408 gene.


spinocerebellar ataxia type 34

A subtype of autosomal dominant cerebellar ataxia type I (ADCA type I), characterized by papulosquamous, ichthyosiform plaques on the limbs appearing shortly after birth and later manifestations including progressive ataxia, dysarthria, nystagmus and decreased reflexes.


This subgroup of myeloproliferative neoplasms includes cases which do not meet the morphologic criteria of any of the defined myeloproliferative neoplasms, or which have characteristics that overlap at least two of the myeloproliferative neoplasms.


46,XX ovotesticular disorder of sex development (46,XX ovotesticular DSD) is characterized by histologically confirmed testicular and ovarian tissue in an individual with a 46,XX karyotype.


ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome


congenital bile acid synthesis defect 1

Congenital bile acid synthesis defect type 1 (BAS defect type 1) is the most common anomaly of bile acid synthesis characterized by variable manifestations of progressive cholestatic liver disease, and fat malabsorption.


congenital left-sided heart lesions

Serious heritable structural anomalies of the left side of the heart, including hypoplastic left heart syndrome, aortic valve stenosis, coarctation of the aorta, mitral valve anomalies and bicuspid aortic valve, that are present from birth.


combined oxidative phosphorylation deficiency 35


ancylostomiasis

Infection by hookworms of the genus Ancylostoma.


primary ciliary dyskinesia 8

A primary ciliary dyskinesia that has material basis in variation in the chromosome region 15q24-q25.


congenital muscular dystrophy-infantile cataract-hypogonadism syndrome

Congenital muscular dystrophy-infantile cataract-hypogonadism syndrome is characterized by congenital muscular dystrophy, infantile cataract and hypogonadism. It has been described in seven individuals from an isolated Norwegian village and in one unrelated individual. Transmission appears to be autosomal recessive.


glucocorticoid deficiency 3

A variant of familial glucocorticoid deficiency caused by a defect in the steroidogenic acute regulatory protein; it may mimic lipoid congenital adrenal hyperplasia.


cerebral sclerosis similar to Pelizaeus-Merzbacher disease


familial temporal lobe epilepsy 5

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


premature aging syndrome

Changes in the organism associated with senescence, occurring at an accelerated rate.


primary pulmonary hypertension

Increased blood pressure in the arteries of the lungs; the etiology is unknown.


neoplasm of cerebral hemisphere

A neoplasm involving a cerebral hemisphere.


GUCY2D retinopathy

Any inherited retinal dystrophy in which the cause of the disease is a mutation in the GUCY2D gene.


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.


ciliary dyskinesia with defective radial spokes


Stickler syndrome, type 4

Any autosomal recessive Stickler syndrome in which the cause of the disease is a mutation in the COL9A1 gene.


alpha-actinopathy

A musculoskeletal system disorder that covers a wide spectrum of phenotypes and is caused by pathogenic variants in the skeletal muscle α-actin gene (ACTA1). These variants lead to a variety of overlapping adult onset and congenital myopathies characterized by muscle weakness, hypotonia, myopathic face, respiratory dysfunction, and rarely cardiac involvement. Specific skeletal muscle structural lesions visible on muscle biopsy include actin accumulations, nemaline and intranuclear bodies, fiber-type disproportion, cores, caps, dystrophic features and zebra bodies. Disorders associated with ACTA1 pathogenic variants can have autosomal dominant (90%) or recessive (10%) inheritance.


disorder of development or morphogenesis

Any disease or disorder that disrupts the process development of an anatomical structure. Can be due to genetic or environmental causes. Typically happens during embryogenesis, but also includes post-embryonic development.


myeloid sarcoma

A tumor mass composed of myeloblasts or immature myeloid cells. It occurs in extramedullary sites or the bone. (WHO, 2001)


nonsyndromic congenital nail disorder 8

Any inherited isolated nail anomaly in which the cause of the disease is a mutation in the COL7A1 gene.


neurodevelopmental disorder and structural brain anomalies with or without seizures and spasticity


alpha thalassemia

Alpha-thalassemia is an inherited hemoglobinopathy characterized by impaired synthesis of alpha-globin chains leading to a variable clinical picture depending on the number of affected alleles.


immunodeficiency 87 and autoimmunity

An autosomal recessive immunologic disorder with wide phenotypic variation and severity. Affected individuals usually present in infancy or early childhood with increased susceptibility to infections, often Epstein-Barr virus (EBV), as well as with lymphadenopathy or autoimmune manifestations, predominantly hemolytic anemia. Laboratory studies may show low or normal lymphocyte numbers, often with skewed T-cell subset ratios. The disorder results primarily from defects in T-cell function, which causes both immunodeficiency and overall immune dysregulation.


amyloidosis cutis dyschromia

Amyloidosis cutis dyschromia is a rare primary cutaneous amyloidosis characterized by macular or reticulate hyperpigmentation with symmetrically distributed guttate hypo- and hyperpigmented lesions which progress gradually over the years to involve almost the entire body (with relative sparing of the face, hands, feet and neck). Patients are usually asymptomatic, however mild pruritus may be associated. Amyloid deposition in the papillary dermis is observed on skin biopsy. Systemic amyloidosis is not present and association with generalized morphea, atypical Parkinsonism, spasticity, motor weakness or colon carcinoma is rare.


faucial diphtheria

Infection of the fauces by Corynebacterium diphtheriae.


atrophic lichen planus

Atrophic lichen planus (LP) is a rare variant of cutaneous lichen planus characterized by the development of pale papules or plaques with an atrophic center.


early-onset progressive encephalopathy-spastic ataxia-distal spinal muscular atrophy syndrome


heterotopia, periventricular, associated with chromosome 5P anomalies


HSD10 disease, infantile type

HSD10 disease, infantile type is a clinical subtype of HSD10 disease, a rare neurometabolic disorder. It is characterized by normal early development until 6-18 months of life, followed by progressive neurodegeneration manifesting with developmental regression, progressive visual and hearing troubles, seizures, epilepsy, severe cardiomyopathy, lethargy, hypotonia, poor feeding, choreoathetosis, and movement disorders. Elevated blood levels of isoleucine metabolites and their excretion in urine are reported. The disease is usually fatal around 2-4 years of age.


iatrogenic Kaposi's sarcoma

A Kaposi sarcoma that develops after organ transplantation or immunosuppressive treatment.


Brugada syndrome 5

Any Brugada syndrome in which the cause of the disease is a mutation in the SCN1B gene.


beta-thalassemia major

Beta-thalassemia (BT) major is a severe early-onset form of BT characterized by severe anemia requiring regular red blood cell transfusions.


citrullinemia, type II, adult-onset

Adult-onset citrullinemia type II is an inherited disorder that causes ammonia and other toxic substances to accumulate in the blood. The condition chiefly affects the nervous system, causing confusion, restlessness, memory loss, abnormal behaviors (such as aggression, irritability, and hyperactivity), seizures, and coma. These signs and symptoms can be life-threatening. The signs and symptoms appear during adulthood and are triggered by certain medications, infections, surgery, and alcohol intake.The features of adult-onset type II citrullinemia may also develop in people who as infants had a liver disorder called neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). In many cases, the signs and symptoms of NICCD resolve within a year. Years or even decades later, however, some of these people develop the characteristic features of adult-onset type II citrullinemia.adult-onset citrullinemia type II is caused by mutations in the SLC25A13 gene. This condition is inherited in an autosomal recessive pattern.


menstrual cycle-dependent periodic fever


congenital heart defects, multiple types, 6

Any dextro-looped transposition of the great arteries in which the cause of the disease is a mutation in the GDF1 gene.


AIDS-related disorder

A non-neoplastic or neoplastic disorder arising as a result of the immunologic defects caused by Autoimmune deficiency Syndrome.


NRXN1-related severe neurodevelopmental disorder-motor stereotypies-chronic constipation-sleep-wake cycle disturbance

A rare, genetic, neurodevelopmental disorder characterized by global developmental delay, severe intellectual disability and absence of expressive language. Muscular hypotonia, seizures, autistic behavior and stereotypic movements are common.


TUBB3-related tubulinopathy

A tubulinopathy syndrome associated with malformations of cortical development, axon guidance defects, white matter abnormalities, and/or congenital fibrosis of the extraocular muscles (CFEOM), due to de novo or dominantly inherited variants with high penetrance. Individuals may present with variable combinations of malformations of cortical development, dysplasia of the basal ganglia, brainstem, and/or cerebellum, CFEOM, additional cranial nerve involvement, Kallmann syndrome, cyclic vomiting, peripheral neuropathy, and/or contractures. Developmental delays, intellectual disability, ocular motor apraxia, and mirror movements are also frequent features.


peroxisome biogenesis disorder 2B

An autosomal recessive condition caused by mutation(s) in the PEX5 gene, encoding peroxisomal targeting signal 1 receptor. Peroxisome biogenesis disorder 2B is characterized by overlapping phenotypes of neonatal adrenoleukodystrophy and infantile Refsum disease.


acquired idiopathic inflammatory myopathy

An umbrella term for diseases which have chronic muscle inflammation and weakness of unknown etiology. The types of idiopathic inflammatory myopathy are further defined by either clinicopathologic criteria or by the presence of certain autoantibodies.


microcephaly 18, primary, autosomal dominant


glutaminase deficiency

Glutaminase deficiency is characterized by refractory seizures, respiratory failure, brain abnormalities and death in the neonatal period, though milder cases with spastic ataxia-dysarthria have also been reported. This condition is caused by mutations in the glutaminase (GLS) gene.


complex cortical dysplasia with other brain malformations


partial duplication of the long arm of chromosome 19


autosomal recessive nonsyndromic hearing loss 38

An autosomal recessive nonsyndromic deafness that has material basis in variation in the chromosome region 6q26-q27.


mixed sclerosing bone dystrophy with extra-skeletal manifestations


extrinsic asthma

A chronic asthma that is triggered by an allergen and that is characterized by an immune system overreaction to a harmless substance, such as pollen or dust, with the subsequent release of immunoglobin E (IgE) antibodies.


Charcot-Marie-Tooth disease, axonal, with vocal cord paresis, autosomal recessive


GTP cyclohydrolase I deficiency

A disease characterized by a deficiency in GTP cyclohydrolase I, which leads to a consequent reduction in BH4 and reduces the activity of three BH4-cofactor dependent enzymes - phenylalanine hydroxylase, tyrosine hydroxylase, and tryptophan hydroxylase. GTP cyclohydrolase I deficiency encompasses a spectrum of disease that includes autosomal dominant and autosomal recessive forms, with severity correlating with the residual enzyme activity. Individuals who are heterozygous for pathogenic variants in GCH1 have symptoms ranging from none (due to reduced penetrance) to dopa-responsive dystonia, which is the most common presentation in symptomatic cases, to rarer neurological presentations such as adult-onset "benign" parkinsonism, various types of focal dystonia, and symptoms simulating cerebral palsy or spastic paraplegia. Hyperphenylalaninemia is absent, and patients respond well to treatment with levodopa. Individuals who are homozygous or compound heterozygous for pathogenic variants in GCH1 typically present with hyperphenylalaninemia, often identified by newborn screening, and severe neurological features and due to very low or undetectable enzyme activity. Treatment with levodopa, BH4, and 5-hydroxytryptophan can improve the symptoms but does not prevent development of severe encephalopathy. Rare cases of GTP cyclohydrolase I deficiency with a phenotype that is intermediate in severity between dopa-responsive dystonia and the severe autosomal recessive form have also been described, supporting the existence a phenotypic spectrum of disease.


combined oxidative phosphorylation deficiency 19

Any combined oxidative phosphorylation deficiency in which the cause of the disease is a mutation in the LYRM4 gene.


actinomycosis

Actinomycosis is a chronic bacterial infection that commonly affects the face and neck. It is usually caused by an anaerobic bacteria called Actinomyces israelii. Actinomyces are normal inhabitants of the mouth, gastrointestinal tract, and female genital tract, and do not cause an infection unless there is a break in the skin or mucosa. The infection usually occurs in the face and neck, but can sometimes occur in the chest, abdomen, pelvis, or other areas of the body. The infection is not contagious.


sarcocystosis

Infection of the striated muscle of mammals by parasites of the genus sarcocystis. Disease symptoms such as vomiting, diarrhea, muscle weakness, and paralysis are produced by sarcocystin, a toxin produced by the organism.


dystonia 16

Dystonia 16 (DYT16) is a very rare and newly discovered movement disorder which is characterized by early-onset progressive limb dystonia, laryngeal and oromandibular dystonia, and parkinsonism.


complex endometrial hyperplasia

A hyperplasia characterized by excessive proliferation of endometrial cells, resulting in the formation of complex epithelial structures. Epithelial atypia may be present or absent.


congenital primary megaureter, obstructed form


Parvoviridae infectious disease

Virus infections caused by the parvoviridae.


hyperphalangy

Hyperphalangy is a congenital, non-syndromic limb malformation characterized by the presence of an accessory phalanx between metacarpal/metatarsal and proximal phalanx, or between any two other phalanges of a digit, excluding the thumb. Hypherphalangy is almost always bilateral and patients present no more than five digits and no other skeletal anomalies.


glycosylphosphatidylinositol biosynthesis defect 16


glucocorticoid-induced osteoporosis

An osteoporosis caused by chronic glucocorticoid use. Glucocorticoids impair the replication, differentiation and function of osteoblasts and induce the apoptosis of mature osteoblasts and osteocytes; the also favor osteoclastogenesis leading to an increase in bone resorption.


atypical autism

Atypical autism is a pervasive developmental disorder that does not fit the diagnosis for the other specific autistic spectrum disorders (autism, Asperger syndrome, Rett syndrome or childhood disintegrative disorder) and is characterized by usually milder developmental and social delay and less stereotypical autistic behavior. '


erythroplakia

A clinical term that refers to the presence of a red flat and well defined lesion on the oral mucosa that is not caused by trauma, vascular, or inflammatory processes. It is a precancerous condition and is seen more commonly in middle aged or older males. It is associated with tobacco and alcohol consumption. Microscopic examination reveals severe epithelial dysplasia, carcinoma in situ, or invasive squamous cell carcinoma.


gonococcal prostatitis

An prostatitis (disease) caused by infection with Neisseria gonorrhoeae.


FOXG1 syndrome

A rare genetic neurological disorder characterized by early onset of microcephaly, severe global developmental delay and cognitive impairment, dyskinesia and hyperkinetic movements, visual impairment, autistic behavior, stereotypies, sleep disturbance, epilepsy, and cerebral malformations (such as corpus callosum hypogenesis, forebrain anomaly, and delayed myelination). Speech is minimal or absent, and ambulation is not attained. Patients with a larger 14q12 microdeletion show a more severe phenotype than those with intragenic alterations, with the addition of facial dysmorphism and agenesis of the corpus callosum.


neuroaxonal dystrophy renal tubular acidosis


fibrochondrogenesis 1

Any fibrochondrogenesis in which the cause of the disease is a mutation in the COL11A1 gene.


autosomal recessive congenital ichthyosis 8

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


chronic cystitis

Recurrent infections of the urinary bladder.


intellectual disability, X-linked 100

Any non-syndromic X-linked intellectual disability in which the cause of the disease is a mutation in the KIF4A gene.


autoimmune interstitial lung disease-arthritis syndrome

A respiratory disease characterized by interstitial lung disease (often with pulmonary hemorrhage) and inflammatory arthritis, associated with high-titer autoantibodies (including anti-nuclear and anti-neutrophil cytoplasmic antibodies, and rheumatoid factor). Patients present from infancy to adolescence with tachypnea, cough, hemoptysis, and/or joint pain. Some patients may also develop glomerular disease.


mosaic trisomy 18

Trisomy 18 in which the presence of an extra copy of chromosome 18 is present only in some of the cells of the organism.


autosomal recessive brachyolmia

Brachyolmia, recessive type is a form of brachyolmia, a group of rare genetic skeletal disorders, characterized by short-trunked short stature with platyspondyly and scoliosis. Corneal opacities and precocious calcification of the costal cartilage are rare syndromic components. Premature pubarche may occur.


congenital cataract-progressive muscular hypotonia-hearing loss-developmental delay syndrome


subglottis cancer

A malignant neoplasm that affects the subglottic area of the larynx. The vast majority of cases are squamous cell carcinomas.


mucopolysaccharidosis type 7

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


benign endocrine neoplasm

A non-metastasizing, functioning or non-functioning neoplasm that arises from an endocrine organ. Representative examples include thyroid gland follicular adenoma and parathyroid gland adenoma.


spondyloepimetaphyseal dysplasia with joint laxity

A form of skeletal dysplasia characterized by severe dwarfism, generalized articular hypermobility, and progressive spinal malalignment.


RET fusion positive cancer

Neoplasm associated with expression of a RET (REarranged during Transfection) fusion. RET fusion-positive tumors have been identified in a broad range of solid tumor types, including multiple endocrine neoplasia 2 (MEN2), papillary thyroid carcinoma (PTC), non-small cell lung cancer (NSCLC), invasive breast cancers, and pancreatic ductal adenocarcinomas in addition to colorectal adenocarcinoma, melanoma, small cell lung cancer, neuroblastoma, and small intestine neuroendocrine tumors.


T-B+ severe combined immunodeficiency due to CD3delta/CD3epsilon/CD3zeta


hypotrichosis 5

A hypotrichosis that has material basis in a mutation on chromosome 1p21.1-q21.3.


familial hemophagocytic lymphohistiocytosis 5

Any genetic hemophagocytic lymphohistiocytosis in which the cause of the disease is a mutation in the STXBP2 gene.


peroxisome biogenesis disorder due to PEX1 defect

Any Zellweger spectrum disorder in which the cause of the disease is a mutation in the PEX1 gene.


cataract-ataxia-deafness syndrome

Cataract-ataxia-deafness syndrome is characterized by mild intellectual deficit, congenital cataract, progressive sensorineural deafness and ataxia. It has been described in two sisters. The inheritance is likely to be autosomal recessive.


Alzheimer disease 2

An Alzheimer's disease that is characterized by an association of the apolipoprotein E E4 allele.


retinitis pigmentosa 57

Any retinitis pigmentosa in which the cause of the disease is a mutation in the PDE6G gene.


von Willebrand disease 2

Type 2 von Willebrand disease (type 2 VWD) is a form of VWD characterized by a bleeding disorder associated with a qualitative deficiency and functional anomalies of the Willebrand factor (von Willebrand factor; VWF).


hemochromatosis type 5

Any hereditary hemochromatosis in which the cause of the disease is a mutation in the FTH1 gene.


benign PEComa

A tumor with perivascular epithelioid cell differentiation characterized by the absence of pleomorphism and scarcity or absence of mitotic figures.


retroperitoneal lymphoma

A lymphoma that involves the retroperitoneal space.


familial hypobetalipoproteinemia 1

Any hypobetalipoproteinemia in which the cause of the disease is a mutation in the APOB gene.


Senior-Loken syndrome 1

Any Senior-Loken syndrome in which the cause of the disease is a mutation in the NPHP1 gene.


rolandic epilepsy-speech dyspraxia syndrome

A rare, genetic epilepsy characterized by speech disorder (including a range of symptoms from dysarthria, speech dyspraxia, receptive and expressive language delay/regression and acquired aphasia to subtle impairments of conversational speech) and epilepsy (mostly focal and secondary generalized childhood-onset seizures, sometimes with aura). Mild to severe intellectual disability may also be observed.


hereditary hypercarotenemia and vitamin A deficiency

Hereditary hypercarotenemia and vitamin A deficiency is an extremely rare metabolic disorder characterized clinically by skin discoloration, elevated levels of carotene and low levels of vitamin A described in fewer than 5 patients to date.


X-linked intellectual disability-spastic quadriparesis syndrome


pulmonary artery coming from patent ductus arteriosus


dystonia 27

Any dystonic disorder in which the cause of the disease is a mutation in the COL6A3 gene.


furuncular myiasis

Furuncular myiasis in humans is caused by two species: the Cayor worm (larvae of the African tumbu fly Cordylobia anthropophaga) and the larvae of the human botfly (Dermatobia hominis).


Lenz-Majewski hyperostotic dwarfism

Lenz-Majewski hyperostotic dwarfism is an extremely rare syndrome associating dwarfism, characteristic facial appearance, cutis laxa and progressive bone sclerosis.


retinitis pigmentosa with or without situs inversus

Any retinitis pigmentosa in which the cause of the disease is a mutation in the ARL2BP gene.


inborn disorder of purine metabolism

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


Elevated levels of plasma valine and leucine/isoleucine levels, associated with symptoms of headache and mild memory loss and attributed to biallelic variants in the BCAT2 gene. BCAT2 encodes branched-chain aminotransferase 2 which catalyzes the transamination of the branched chain amino acids to their respective α-keto acids.


deafness-lymphedema-leukemia syndrome

Deafness - lymphedema - leukemia is a very rare, serious syndromic genetic disorder characterized by primary lymphedema, immunodeficiency, and hematological disorders.


familial renal glucosuria

Familial Renal Glucosuria (FRG) is characterized by the presence of persistent isolated glucosuria in the absence of both generalized proximal tubular dysfunction and hyperglycemia. FRG is usually considered a benign entity as most patients are not affected by severe clinical consequences. Polyuria and enuresis and later a mild growth and pubertal maturation delay are the only manifestations that have been reported during a follow-up period of 30 years. Episodic dehydration and ketosis during pregnancy and starvation and an increased incidence of urinary tract infections have occasionally been reported in severe cases. FRG is caused by loss-of-function mutations in the gene SLC5A2 (16p11.2).


platelet-type von Willebrand disease

A bleeding disorder characterized by mild to moderate mucocutaneous bleeding, which becomes more pronounced during pregnancy or following ingestion of drugs that have anti-platelet activity. PT-VWD is due to hyperresponsive platelets, resulting in thrombocytopenia.


microcephalic osteodysplastic primordial dwarfism


Gomez-Lopez-Hernandez syndrome

A syndrome, which may be classified among the neurocutaneous syndromes, associates abnormalities of the cerebellum (rhombencephalosynapsis), cranial nerves (trigeminal anesthesia), and scalp (alopecia). It has been reported in 11 individuals so far. Other features observed in patients were craniosynostosis, midfacial hypoplasia, bilateral corneal opacities, low-set ears, short stature, moderate intellectual impairment and ataxia. Hyperactivity, depression, self-injurious behavior and bipolar disorder have also been reported.


zinc-responsive necrolytic acral erythema


cardiovascular cancer

A primary or metastatic malignant neoplasm involving the cardiovascular system.


mitochondrial short-chain Enoyl-Coa hydratase 1 deficiency

An autosomal recessive condition caused by mutation(s) in the ECHS1 gene, encoding enoyl-CoA hydratase, mitochondrial. The condition represents a clinical spectrum in which there are multiple phenotypes.


amelogenesis imperfecta type 1G

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


inborn disorder of serine family metabolism

An inherited metabolic disease that is has its basis in the disruption of serine family amino acid metabolic process.


Bicervical bicornuate uterus and blind hemivagina


qualitative or quantitative protein defects in neuromuscular diseases


familial hyperaldosteronism

Familial hyperaldosteronism (FH) is the heritable form of primary aldosteronism (PA) which comprises three identified subtypes to date: FH type I (FH-I) characterized by early-onset hypertension, glucocorticoid remediable adrenocorticotropic hormone (ACTH)-dependent hyperaldosteronism, variable hypokalemia, and overproduction of 18-oxocortisol and 18-hydroxycortisol; FH type II (FH-II) characterized by hypertension of varying severity and hyperaldosteronism not suppressible by dexamethasone; and FH type III (FH-III) characterized by profound hypokalemia, early-onset severe hypertension, non glucocorticoid-remediable hyperaldosteronism, and overproduction of 18-oxocortisol and 18-hydroxycortisol.


developmental and epileptic encephalopathy 31B


tooth agenesis, selective, 7

Any tooth agenesis in which the cause of the disease is a mutation in the LRP6 gene.


melorheostosis with osteopoikilosis

Melorheostosis with osteopoikilosis is a rare sclerosing bone dysplasia, combining the clinical and radiological features of melorheostosis and osteopoikilosis, that has been reported in some families with osteopoikilosis and that is characterized by a variable presentation of limb pain and deformities.


platelet-type bleeding disorder 12

An inherited blood coagulation disease characterized by autosomal dominant inheritance of mildly increased bleeding, platelet aggregation defect, and impaired conversion of arachidonic acid to thromboxane A2 in platelets due to deficiency in PTGS1 activity.


parietal foramina with cleidocranial dysplasia

Parietal foramina with clavicular hypoplasia is a rare genetic bone development disorder characterized by parietal foramina in association with hypoplasia of the clavicles (short abnormal clavicles with tapering lateral ends, with or without loss of the acromion). Additional features may include mild craniofacial dysmorphism (macrocephaly, broad forehead and frontal bossing). No dental abnormalities were reported.


trombiculiasis

Infestation with mites of the genus Trombiculidae, whose larvae carry the rickettsial agent of scrub typhus.


Nematoda infectious disease

Infections caused by nematode larvae which never develop into the adult stage and migrate through various body tissues. They commonly infect the skin, eyes, and viscera in humans. Ancylostoma brasiliensis causes cutaneous larva migrans. Toxocara causes visceral larva migrans.


epiphyseal dysplasia, multiple, 6

Any multiple epiphyseal dysplasia in which the cause of the disease is a mutation in the COL9A1 gene.


familial Dupuytren contracture

Familial Dupuyren contracture is a rare, genetic, epidermal disease characterized by a, usually unilateral, progressive thickening and shortening of the palmar fascia, leading to permanent flexion contracture of the digits in several members of a family. It most commonly affects the fourth digit, followed by the fifth and then the third (first and second digits are usually spared).


spondyloepiphyseal dysplasia congenita

A chondrodysplasia characterized by disproportionate short stature, abnormal epiphyses and flattened vertebral bodies.


peeling skin syndrome 1

Any peeling skin syndrome in which the cause of the disease is a mutation in the CDSN gene.


axonal polyneuropathy associated with IgG/IgM/IgA monoclonal gammopathy


Adams-Oliver syndrome 3

Any Adams-Oliver syndrome in which the cause of the disease is a mutation in the RBPJ gene.


This syndrome is characterized by bilateral congenital blepharoptosis, ectopia lentis and high myopia.


KBG syndrome

KBG syndrome is a rare condition characterized by a typical facial dysmorphism, macrodontia of the upper central incisors, skeletal (mainly costovertebral) anomalies and developmental delay.


transaldolase deficiency

Transaldolase deficiency is an inborn error of the pentose phosphate pathway that presents in the neonatal or antenatal period with hydrops fetalis, hepatosplenomegaly, hepatic dysfunction, thrombocytopenia, anemia, and renal and cardiac abnormalities.


pneumonic pasteurellosis

Bovine respiratory disease found in animals that have been shipped or exposed to cattle recently transported. The major agent responsible for the disease is mannheimia haemolytica and less commonly, pasteurella multocida or haemophilus somnus. All three agents are normal inhabitants of the bovine nasal pharyngeal mucosa but not the lung. They are considered opportunistic pathogens following stress, physiological and/or a viral infection. The resulting bacterial fibrinous bronchopneumonia is often fatal.


dyskeratosis congenita, X-linked

X-linked form of dyskeratosis congenita.


hereditary spastic paraplegia 37

Autosomal dominant spastic paraplegia type 37 is a pure form of hereditary spastic paraplegia characterized by a childhood- to adulthood-onset of slowly progressive spastic gait, extensor plantar responses, brisk tendon reflexes in arms and legs, decreased vibration sense at ankles and urinary dysfunction. Ankle clonus is also reported in some patients.


endometrioid stromal and related neoplasms of the vagina

A category of rare neoplasms that arise from the vagina. It includes low grade endometrioid stromal sarcoma and undifferentiated sarcoma.


RP1-related recessive retinopathy

An autosomal dominant retinopathy caused by variants in the RP1 gene.


chromosome 17q12 duplication syndrome

17q12 microduplication syndrome is a rare chromosomal anomaly with variable phenotypic expression and reduced penetrance associated with developmental delay, mild to severe intellectual disability, speech delay, seizures, microcephaly, behavioral abnormalities, autism spectrum disorder, eye or vision defects (such as strabismus, astigmatism, amblyopia, cataract, coloboma, and microphthalmia), non-specific dysmorphic features, hypotonia, cardiac and renal anomalies, schizophrenia.


cavitary myiasis

Cavitary myiasis is a rare parasitic disease characterized by the infestation of natural body cavities (e.g. aural, nasal, oral, urogenital myiasis) and internal organs (e.g. cerebral myiasis, ophthalmomyiasis, intestinal and tracheopulmonary myiasis) with dipteran larvae. Clinical presentation is variable depending on the affected site(s) and degree of infestation and include foreign-body sensation (with or without movement sensation), hemorrhage, pain, edema, sensory loss, malodor, and pruritus, among others. Neurological features (e.g. motor deficits, seizures, reduced mental status, extrapyramidal signs) have been reported in cerebral myiasis.


angiomyxoma

A benign soft tissue neoplasm characterized by the presence of neoplastic spindle and stellate cells, and vascular proliferation in a myxoid stroma.


NARP syndrome

Neuropathy, Ataxia, and Retinitis Pigmentosa (NARP) syndrome is a clinically heterogeneous progressive condition characterized by a combination of proximal neurogenic muscle weakness, sensory-motor neuropathy, ataxia, and pigmentary retinopathy.


keratosis palmaris et plantaris-clinodactyly syndrome

Keratosis palmaris et plantaris-clinodactyly syndrome is characterized by the association of palmoplantar keratosis with clinodactyly of the fifth finger. Less than 20 cases have been described in the literature so far, and the majority of reported patients were of Mexican origin. Transmission is autosomal dominant.


inborn disorder of phenylalanine and tyrosine metabolism


Microcephaly-brachydactyly-kyphoscoliosis syndrome is characterized by profound intellectual deficit in association with microcephaly, short stature, brachydactyly type D, a flattened occiput, downslanting palpebral fissures, low-set large ears, a broad prominent nose and kyphoscoliosis. It has been described in three sisters. The disorder is likely to be transmitted as an autosomal recessive trait.


inherited Fanconi renotubular syndrome

An instance of Fanconi renotubular syndrome that is inherited.


pancytopenia due to IKZF1 mutations

Any syndrome with combined immunodeficiency in which the cause of the disease is a mutation in the IKZF1 gene.


resistance to thyroid hormone due to a mutation in thyroid hormone receptor alpha


action myoclonus-renal failure syndrome

Action myoclonus-renal failure syndrome (AMRF) is a rare epilepsy syndrome characterized by progressive myoclonus epilepsy in association with primary glomerular disease. Patients present with neurologic symptoms (including tremor, action myoclonus, tonic-clonic seizures, later ataxia and dysarthria) that may precede, occur simultaneously or be followed by renal manifestations including proteinuria that progresses to nephrotic syndrome and end-stage renal disease. In some patients, sensorimotor peripheral neuropathy, sensorineural hearing loss and dilated cardiomyopathy are associated symptoms.


intellectual disability, autosomal recessive 28


facial paresis, hereditary congenital, 1


rapadilino syndrome

RAPADILINO syndrome is a syndrome for which the acronym indicates the principal signs: RA for radial ray defect, PA for both patellae hypoplasia or aplasia and cleft or highly arched palate, DI for diarrhea and dislocated joints, LI for little size and limb malformations, NO for long, slender nose and normal intelligence.


Stevens-Johnson syndrome/toxic epidermal necrolysis overlap syndrome


bone marrow neoplasm

Neoplasms that affect the bone marrow. Such neoplasms may arise in the bone marrow (e.g. myeloid leukemias) or may involve the bone marrow as secondary, metastatic tumors (e.g. metastatic carcinomas to the bone marrow).


interstitial granulomatous dermatitis with arthritis

Interstitial granulomatous dermatitis with arthritis is a rare rheumatologic disease characterized by the occurrence of inflammatory arthritis in association with large, erythematous, symmetrical cutaneous lesions (ranging from typical, but infrequent, cord-like lesions on the flanks to more common violaceous plaques on the trunk and limbs) featuring a typical histologic infiltrate mainly constituted of histiocytes.


epilepsy of infancy with migrating focal seizures

This syndrome is characterized by onset of refractory focal seizures in the first year of life, with associated severe encephalopathy. Focal seizures arise independently in both hemispheres and can migrate from one cortical region to another randomly but consecutively in the same seizure. Seizures are often prolonged with episodes of status epilepticus. Prognosis is poor with severe neurological disability and reduced life expectancy, although a milder evolution has been reported in a few children.


acquired laryngomalacia

A laryngeal disease that is characterized by acquired collapse of laryngeal suprastructures.


congenital disorder of glycosylation, type IIaa


familial juvenile hyperuricemic nephropathy type 2

Familial juvenile hyperuricemic nephropathy type 2 is a rare autosomal dominantly inherited disease of childhood characterized by hypoproliferative anemia, hyperuricemia and slowly progressing kidney failure due to dysregulation of the renin-angiotensin system (RAS).


hereditary spastic paraplegia 8

Any hereditary spastic paraplegia in which the cause of the disease is a mutation in the WASHC5 gene.


mitochondrial complex 1 deficiency, nuclear type 11


autosomal recessive nonsyndromic hearing loss 65

An autosomal recessive nonsyndromic deafness that has material basis in variation in the chromosome region 20q13.2-q13.3.


episodic ataxia type 2

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


spotted fever

A type of tick-borne disease which presents on the skin caused by bacteria of the genus Rickettsia.


autosomal dominant limb-girdle muscular dystrophy type 1F

Autosomal dominant limb-girdle muscular dystrophy type 1F (LGMD1F) is a subtype of autosomal dominant limb-girdle muscular dystrophy,with a variable age of onset, characterized by progressive, proximal weakness and wasting of the shoulder and pelvic musculature (with the pelvic girdle, and especially the ileopsoas muscle, being more affected) and frequent association of calf hypertrophy, dysphagia, arachnodactyly with or without finger contractures and/or distal and axial muscle involvement. Additional features include an abnormal gait, exercise intolerance, myalgia, fatigue and respiratory insufficiency. Cardiac conduction defects are typically not observed.


radioulnar synostosis with amegakaryocytic thrombocytopenia 1

Any radio-ulnar synostosis-amegakaryocytic thrombocytopenia syndrome in which the cause of the disease is a mutation in the HOXA11 gene.


encephalopathy due to hydroxykynureninuria

Encephalopathy due to hydroxykynureninuria is characterized by psychomotor retardation and nonprogressive encephalopathy associated with urinary excretion of large amounts of kynurenine, 3-hydroxykynurenine, and xanthurenic acid. It has been described in less than 30 patients. Other manifestations may include muscular hypertonia, headaches and stereotyped gestures. This disorder is transmitted as an autosomal recessive trait. It is caused by a defect in kynureninase, an enzyme of the tryptophane catabolic pathway.


X-linked intellectual disability-macrocephaly-macroorchidism syndrome is characterized by intellectual deficit affecting both sexes, macrocephaly, and macroorchidism in the majority of affected males. It has been described in 12 individuals from two generations of one family. Other males from this family did not display intellectual deficit but did present macroorchidism and macrocephaly. Transmission is X-linked and the causative gene has been localized to the q12-q21 region of the X chromosome.


15q14 microdeletion syndrome

15q14 microdeletion syndrome is a recently described syndrome characterized by developmental delay, short stature and facial dysmorphism.


lymphatic malformation 1

Any hereditary lymphedema in which the cause of the disease is a mutation in the FLT4 gene.


congenital lactic acidosis, Saguenay-Lac-Saint-Jean type

Saguenay-Lac-St. Jean (SLSJ) type congenital lactic acidosis, a French Canadian form of Leigh syndrome, is a mitochondrial disease characterized by chronic metabolic acidosis, hypotonia, facial dysmorphism and delayed development.


split-hand/foot malformation with long bone deficiency 2


autosomal dominant nocturnal frontal lobe epilepsy 3

Any autosomal dominant nocturnal frontal lobe epilepsy in which the cause of the disease is a mutation in the CHRNB2 gene.


hereditary spastic paraplegia 75

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


miliary tuberculosis

I would say the hematogenous widespread dissemination of tuberculosis in the body. The term derives from the chest X-ray image of the tiny (1-5 mm) tuberculosis lesions which are seen through out the lung parenchyma.


desmoplastic small round cell tumor

Desmoplastic small round cell tumor (DSRCT) is an aggressive soft tissue cancer that typically arises in serous lined surfaces of the abdominal or pelvic peritoneum, and spreads to the omentum, lymph nodes and hematogenously disseminates especially to the liver. Extraserous primary location has been reported in exceptional cases.


thromboangiitis obliterans

A rare inflammatory non-necrotizing vascular disease affecting the small- and medium-sized arteries and veins of the upper and lower extremities characterized by endarteritis and vaso-occlusion due to occlusive thrombus development. The development and progression of the disease is consistently associated with exposure to tobacco.


9p13 microdeletion syndrome

9p13 microdeletion syndrome is a rare chromosomal anomaly syndrome, resulting from a partial interstitial deletion of the short arm of chromosome 9, characterized by mild to moderate developmental delay, hand tremors, myoclonic jerks, attention deficit-hyperactivity disorder and a social personality. Patients also present bruxism, short stature and minor facial dysmorphic features (e.g., bilateral epicantic folds, broad, flat nasal bridge, anteverted nares, low-set ears micro/retro-gnathia).


hereditary thrombophilia due to congenital protein S deficiency

Congenital protein S deficiency is an inherited coagulation disorder characterized by recurrent venous thrombosis symptoms due to reduced synthesis and/or activity levels of protein S.


secondary hypoparathyroidism due to impaired parathormon secretion


intellectual disability, autosomal recessive 34

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


atypical depressive disorder

A mood disorder that is characterized by mood reactivity (paradoxical anhedonia) and positivity, significant weight gain or increased appetite ("comfort eating"), excessive sleep or somnolence (hypersomnia), a sensation of heaviness in limbs known as leaden paralysis, and significant social impairment as a consequence of hypersensitivity to perceived interpersonal rejection.


soft tissue amyloid neoplasm

A soft tissue neoplasm composed of acellular amyloid material.


hypotonic cerebral palsy

A type of cerebral palsy characterized by decreased muscle tone.


glycogen storage disease due to glycogen branching enzyme deficiency, fatal perinatal neuromuscular form


hemolytic anemia due to adenylate kinase deficiency

Hemolytic anemia due to adenylate kinase deficiency is a rare hemolytic anemia due to an erythrocyte nucleotide metabolism disorder characterized by moderate to severe chronic nonspherocytic hemolytic anemia that may require regular blood transfusions and/or splenectomy and may be associated with psychomotor impairment.


intellectual developmental disorder, autosomal recessive 75, with neuropsychiatric features and variant lissencephaly


hypogonadotropic hypogonadism 9 with or without anosmia

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


Alexander disease

Alexander disease (AxD) is a rare neurodegenerative disorder of the astrocytes comprised of two clinical forms: AxD Type I and Type II manifesting with various degrees of macrocephaly, spasticity, ataxia and seizures and leading to psychomotor regression and death.


Hb Bart's hydrops fetalis

Hb Bart's hydrops fetalis is the most severe form of alpha-thalassemia and is almost always lethal. It is characterized by fetal onset of generalized edema, pleural and pericardial effusions, and severe hypochromic anemia.


primary ciliary dyskinesia 2

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


pernicious anemia

Megaloblastic anemia caused by vitamin B-12 deficiency due to impaired absorption. The impaired absorption of vitamin B-12 is secondary to atrophic gastritis and loss of gastric parietal cells.


hereditary periodic fever syndrome

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


microcephaly 6, primary, autosomal recessive

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


Charcot-Marie-Tooth disease type 2J

Autosomal dominant Charcot-Marie-Tooth disease type 2J (CMT2J) is a form of axonal Charcot-Marie-Tooth disease, a peripheral sensorimotor neuropathy, characterized by a relatively late onset, pupillary abnormalities and deafness, in most patients, associated with distal weakness and muscle atrophy.


autosomal recessive nonsyndromic hearing loss 45

An autosomal recessive nonsyndromic deafness that has material basis in variation in the chromosome region 1q43-q44.


amyotrophic lateral sclerosis type 12

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


chromosome 19p13.13 deletion syndrome

19p13.13 microdeletion syndrome is a rare partial autosomal monosomy characterized by global developmental delay, moderate intellectual disability, macrocephaly, overgrowth, hypotonia, and facial dysmorphism (frontal bossing, down-slanting palpebral fissures). Other associated features variably include ataxia, seizures, ventriculomegaly, ocular abnormalities (strabismus, optic nerve hypoplasia) and gastrointestinal problems (abdominal pain, vomiting, constipation).


cloverleaf skull-multiple congenital anomalies syndrome

This newly described syndrome is characterized by cloverleaf skull, limb anomalies, facial dysmorphism and multiple congenital anomalies.


osteogenesis imperfecta type 13

Any osteogenesis imperfecta in which the cause of the disease is a mutation in the BMP1 gene.


neuroendocrine disorder

A disease or disorder that affects the neuroendocrine gland, any of the organized aggregations of cells that function as secretory or excretory organs and that release hormones in response to neural stimuli.


C syndrome

C syndrome is a rare multiple congenital anomaly/intellectual disability syndrome characterized by trigonocephaly and metopic suture synostosis, dysmorphic facial features, short neck, skeletal anomalies, and variable intellectual disability.


An extremely rare autosomal recessive glycine metabolism disorder characterized clinically in the single reported case to date by muscle fatigue and a fish-like odor. This is an n-of-1 use case where only one patient or family has been described with this disorder.


intellectual disability, X-linked, with or without seizures, arx-related


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.


iris cancer

A malignant neoplasm involving the iris.


hereditary hemorrhagic telangiectasia type 4


hyperinsulinemic hypoglycemia, familial, 8


vaginal melanoma

A primary malignant neoplasm of the vagina composed of malignant melanocytes.


hyperphosphatasia with intellectual disability syndrome 6

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


multinodular and vacuolating neuronal tumor

A central nervous system benign neoplasm that is composed of cells with glial and/or neuronal differentiation forming multiple nodules with prominent vacuolation and that affecting the cerebral hemispheres.


hereditary spastic paraplegia 3A

Any hereditary spastic paraplegia in which the cause of the disease is a mutation in the ATL1 gene.


TSPAN12-related vitreoretinopathy

A vitreoretinopathy caused by variants in the TSPAN12 gene.


parametritis

Inflammation of the parametrium, the connective tissue of the pelvic floor, extending from the subserous coat of the uterus laterally between the layers of the broad ligament.


hypophosphatemic rickets, autosomal recessive, 1

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


hypogonadotropic hypogonadism 25 with anosmia


cataract 39 multiple types

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


developmental and epileptic encephalopathy, 70


heterophyiasis

An infection that is caused by the intestinal fluke Heterophyes heterophyes, which is most commonly found in Asia, the Middle East, and Africa, and which is transmitted via consumption of contaminated raw or undercooked fish. Symptoms typically range from asymptomatic to intermittent abdominal pain and diarrhea, with occasional ectopic infection.


hereditary spherocytosis type 4

Any hereditary spherocytosis in which the cause of the disease is a mutation in the SLC4A1 gene.


microcephaly 19, primary, autosomal recessive


streptococcal toxic-shock syndrome

Streptococcal toxic-shock syndrome (streptococcal TSS) is an acute disease mediated by the production of superantigenic toxins characterized by the sudden onset of fever and other febrile symptoms, pain, multisystem organ involvement and potentially leading to coma, shock and death due to a Streptococcus pyogenes infection.


autosomal recessive ataxia due to ubiquinone deficiency

This syndrome is characterized by childhood-onset progressive ataxia and cerebellar atrophy.


autoimmune disorder of peripheral nervous system

A hypersensitivity reaction type II disease that involves the peripheral nervous system.


Ehlers-Danlos syndrome, musculocontractural type is a congenital form of Ehlers-Danlos syndrome characterized by distinct craniofacial features, multiple contractures, progressive joint and skin laxity, adduction-flexion contractures of the thumbs, talipes equinovarus, bruisability and multisystem fragility-related manifestations.


familial clubfoot due to PITX1 point mutation


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).


chronic neurovisceral acid sphingomyelinase deficiency


retinal drusen

Colloid or hyaline bodies lying beneath the retinal pigment epithelium. They may occur either secondary to changes in the choroid that affect the pigment epithelium or as an autosomal dominant disorder of the retinal pigment epithelium.


20p13 microdeletion syndrome

20p13 microdeletion syndrome is a rare chromosomal anomaly characterized by developmental delay, mild to moderate intellectual disability, epilepsy, and unspecific dysmorphic signs. High palate, delayed permanent tooth eruption, hypoplastic fingernails, clinodactyly and short fingers have also been reported.


atrial septal defect 6

Any atrial heart septal defect in which the cause of the disease is a mutation in the TLL1 gene.


solitary osseous plasmacytoma

A localized, clonal (malignant) plasma cell infiltrate in the bone, without peripheral blood involvement. The most commonly affected bones are the vertebrae, ribs, skull, pelvis and femur. X-rays examination reveals a solitary lytic lesion.


cone-rod dystrophy 5

Any cone-rod dystrophy in which the cause of the disease is a mutation in the PITPNM3 gene.


TTN-related myopathy

A disorder of the musculoskeletal system caused by pathogenic variants in the TTN gene encoding the titin protein expressed in striated muscle. These variants are associated with a variety of overlapping congenital and adult-onset myopathies characterized by non-progressive or progressive neck, axial, and limb weakness, joint contractures, early-onset respiratory insufficiency, facial weakness, congenital cardiac anomalies and/or early-onset dilated cardiomyopathy. Histologic findings on skeletal muscle biopsy reveal a wide range of structural abnormalities and can include increased internalized and central nuclei, minicores, and dystrophic changes.


piedra

Either of two diseases resulting from fungal infection of the hair shafts. Black piedra occurs mainly in and on the hairs of the scalp and is caused by Piedraia hortae; white piedra occurs in and on the hairs of the scalp, beard, mustache and genital areas and is caused by Trichosporon species.


uterine corpus adenocarcinofibroma

A adenocarcinofibroma that involves the body of uterus.


isolated congenital ectropion

A congenital ectropion that is not part of a larger syndrome.


TEK-related primary glaucoma

Any primary hereditary glaucoma in which the cause of the disease is a mutation in the TEK gene.


mesomelic dysplasia, Kantaputra type

Mesomelic dysplasia Kantaputra type (MDK) is a rare skeletal disease characterized by symmetric shortening of the middle segments of limbs and short stature.


autoimmune disorder of central nervous system

A hypersensitivity reaction type II disease that involves the central nervous system.


retinitis pigmentosa 17

Any retinitis pigmentosa in which the cause of the disease is a mutation in the CA4 gene.


vitelliform macular dystrophy 2

Best vitelliform macular dystrophy (BVMD) is a genetic macular dystrophy characterized by loss of central visual acuity, metamorphopsia and a decrease in the Arden ratio secondary to an egg yolk-like lesion located in the foveal or parafoveal region.


intellectual disability, autosomal recessive 14

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


mucopolysaccharidosis type 6, slowly progressing


complete trisomy 13

Trisomy 13 in which the presence of an extra copy of chromosome 13 is present in all the cells of the organism.


neurodevelopmental disorder with motor and speech delay and behavioral abnormalities


partial trisomy of the long arm of chromosome 20