TaoMedAI/RareMedData huggingface dataset:
Autosomal dominant generalized epidermolysis bullosa simplex, intermediate form (ORPHA:79399)
Non-Dowling-Meara generalized epidermolysis bullosa simplex, formerly known as epidermolysis bullosa simplex, Köbner type (EBS-K) is a generalized basal subtype of epidermolysis bullosa simplex (EBS, see this term) characterized by non-herpetiform blisters and erosions arising in particular at sites of friction.
Epidemiology
Worldwide prevalence is unknown but in Scotland reported overall prevalence of non-Dowling-Meara generalized EBS and localized EBS is 1/35,000.
Clinical description
Onset of the disease is usually at birth. Blistering tendency usually worsens in summertime (or in warm weather). The frequency of milia, mild atrophic scarring, focal plantar hyperkeratosis and nail dystrophy is intermediate between that of localized EBS and EBS-DM (see these terms), and extracutaneous findings, other than occasional intraoral blistering, are rare. Given the considerable overlap between non-Dowling-Meara EBS and localized EBS within some kindreds, some experts prefer to group both subtypes together.
Etiology
Non-Dowling-Meara EBS is caused by dominant negative mutations within either the KRT5 (12q13.13) or KRT14 (17q12-q21) genes, encoding keratin 5 and keratin 14, respectively.
Genetic counseling
Transmission is autosomal dominant and sporadic cases are frequent.
Prognosis
Although the disease can be severely disabling, life-expectancy is normal.

                            Last update: 
                            May 2012


                            - Expert reviewer(s): 
                            Pr Giovanna ZAMBRUNO
Autosomal dominant generalized epidermolysis bullosa simplex, severe form (ORPHA:79396)
Epidermolysis bullosa simplex, Dowling-Meara type (EBS-DM) is a basal subtype of epidermolysis bullosa simplex (EBS, see this term) characterized by the presence of generalized vesicles and small blisters in grouped or arcuate configuration.
Epidemiology
Worldwide prevalence is unknown but reported prevalence in Scotland is 1/1,700,000.
Clinical description
Onset is usually at birth with large, frequently hemorrhagic blisters. After the neonatal period, the lesions take the typical herpetiform (or herpes-like) clustering with central healing pattern. Blister formation gradually reduces starting from late childhood. By childhood, most patients begin to develop confluent thickening and hyperkeratosis (keratoderma) of the palms and soles which may partially resolve in some patients during mid- to late-adulthood. Along with blisters, skin findings commonly include mild atrophic scarring and post-inflammatory pigmentation, nail shedding and nail dystrophy, as well as occasional milia formation. Lesions may improve in some patients in case of fever, unlike other forms of EB in which warmer weather exacerbates disease activity. The reason for this is unknown. Extracutaneous complications can occur including oral cavity blistering, constipation and, rarely, tracheolaryngeal compromise.
Etiology
EBS-DM is caused by dominant negative mutations within either the KRT5 (12q13.13) or KRT14 (17q12-q21) genes, encoding keratin 5 and keratin 14, respectively.
Genetic counseling
Transmission is autosomal dominant and sporadic cases are frequent.
Prognosis
EBS-DM is frequently associated with marked morbidity in infancy and early childhood and, in rare cases, may result in death during early infancy. Patients also have a markedly increased risk of basal cell carcinoma by mid-adulthood (cumulative risk of 44% by age 55).

                            Last update: 
                            May 2012


                            - Expert reviewer(s): 
                            Pr Giovanna ZAMBRUNO
Autosomal dominant hyperinsulinism due to Kir6.2 deficiency (ORPHA:276580)
A form of diazoxide-sensitive diffuse hyperinsulinism (DHI) characterized by hypoglycemic epiosodes that are usually mild, escaping detection during infancy, and usually a good clinical response to diazoxide, (but some are diazoxide resistant). Autosomal dominant hyperinsulinism due to Kir6.2 deficiency usually has a milder phenotype when compared to that resulting from recessive K+ (K-ATP) channel mutations (Recessive forms of diazoxide-resistant hyperinsulinism).
Autosomal dominant hyperinsulinism due to SUR1 deficiency (ORPHA:276575)
A form of congenital diazoxide-sensitive diffuse hyperinsulinism due to ABCC8 variants and characterized by hypoglycemic episodes that are usually mild, escaping detection during infancy, and usually have a good clinical response to diazoxide. The autosomal dominant hyperinsulinism usually has a milder phenotype when compared to that resulting from recessive potassium (K-ATP) channel mutations.
Autosomal dominant intermediate Charcot-Marie-Tooth disease type A (ORPHA:100043)
A rare hereditary motor and sensory neuropathy characterized by intermediate motor median nerve conduction velocities (usually between 25 and 45 m/s) and signs of both demyelination and axonal degeneration in nerve biopsies. It presents with usual clinical features of Charcot-Marie-Tooth disease (progressive muscle weakness and atrophy of the distal extremities, distal sensory loss, reduced or absent deep tendon reflexes, and feet deformities) in the first to second decade of life with steady progression until the fourth decade, severe progression and stabilization afterwards.
Autosomal dominant intermediate Charcot-Marie-Tooth disease type B (ORPHA:100044)
A rare hereditary motor and sensory neuropathy characterized by intermediate motor median nerve conduction velocities (usually between 25 and 45 m/s) and signs of both demyelination and axonal degeneration in nerve biopsies. It presents with mild to moderately severe, slowly progressive usual clinical features of Charcot-Marie-Tooth disease (muscle weakness and atrophy of the distal extremities, distal sensory loss, reduced or absent deep tendon reflexes, and feet deformities). Other findings include asymptomatic neutropenia and early-onset cataracts.
Autosomal dominant intermediate Charcot-Marie-Tooth disease type C (ORPHA:100045)
A rare hereditary motor and sensory neuropathy characterized by intermediate motor median nerve conduction velocities (usually between 25 and 60 m/s). It presents with moderately severe, slowly progressive usual clinical features of Charcot-Marie-Tooth disease (muscle weakness and atrophy of the distal extremities, distal sensory loss, reduced or absent deep tendon reflexes, feet deformities, extensor digitorum brevis atrophy). Findings in nerve biopsies include age-dependent axonal degeneration, reduced number of large myelinated fibres, segmental remyelination, and no onion bulbs.
Autosomal dominant intermediate Charcot-Marie-Tooth disease type D (ORPHA:100046)
A rare hereditary motor and sensory neuropathy characterized by intermediate motor median nerve conduction velocities (usually between 25 and 45 m/s) and signs of both axonal degeneration and demyelination without onion bulbs in nerve biopsies. It presents with usual Charcot-Marie-Tooth disease clinical features of variable severity (progressive muscle weakness and atrophy of the distal extremities, distal sensory loss, reduced or absent deep tendon reflexes, and feet deformities). Other findings in some of the families include debilitating neuropathic pain and mild postural/kinetic upper limb tremor.
Autosomal dominant intermediate Charcot-Marie-Tooth disease type E (ORPHA:93114)
A rare hereditary motor and sensory neuropathy disorder characterized by the typical CMT phenotype (slowly progressive distal muscle weakness and atrophy in upper and lower limbs, distal sensory loss in extremities, reduced or absent deep tendon reflexes and foot deformities) associated with focal segmental glomerulosclerosis (manifesting with proteinuria and progression to end-stage renal disease). Mild or moderate sensorineural hearing loss may also be associated. Nerve biopsy reveals both axonal and demyelinating changes and nerve conduction velocities vary from the demyelinating to axonal range (typically between 25-50m/sec).
Autosomal dominant intermediate Charcot-Marie-Tooth disease type F (ORPHA:352670)
A rare hereditary motor and sensory neuropathy disorder characterized by the typical CMT phenotype (slowly progressive distal muscle atrophy and weakness in upper and lower limbs, distal sensory loss in extremities, reduced or absent deep tendon reflexes and foot deformities) with nerve biopsy demonstrating demyelinating and axonal changes and nerve conduction velocities varying from the demyelinating to axonal range.
Autosomal dominant intermediate Charcot-Marie-Tooth disease with neuropathic pain (ORPHA:324585)
A rare subtype of autosomal dominant intermediate Charcot-Marie-Tooth disease characterized by debilitating neuropathic pain associated with mild, distal, symmetrical lower limb sensory loss and mild or absent motor dysfunction. Patients typically manifest with burning, aching, shooting, or throbbing pain and intermittent paraesthesia in toes, heels and ankles.
Autosomal dominant Kenny-Caffey syndrome (ORPHA:93325)
A rare, primary bone dysplasia characterized by severe growth retardation, short stature, cortical thickening and medullary stenosis of long bones, delayed closure of the anterior fontanelle, absent diploic space in the skull bones, prominent forehead, macrocephaly, dental anomalies, eye problems (hypermetropia and pseudopapilledema), and hypocalcemia due to hypoparathyroidism, sometimes resulting in convulsions. Intelligence is normal.
Autosomal dominant keratitis (ORPHA:2334)
A rare genetic inflammatory corneal disorder characterized by anterior stromal corneal opacification and vascularization of the peripheral cornea with potential central progression and subsequent reduction in visual acuity. Variable features include abnormalities of the iris, such as stromal defects and ectropion uveae, as well as foveal hypoplasia.
Autosomal dominant limb-girdle muscular dystrophy type 1A (ORPHA:266)
A rare subtype of autosomal dominant limb girdle muscular dystrophy characterized by an adult onset of proximal shoulder and hip girdle weakness (that later progresses to include distal weakness), nasal speech and dysarthria. Other frequent findings include tightened heel cords, reduced deep-tendon reflexes and elevated creatine kinase serum levels. Respiratory failure, as well as mild facial weakness and dysphagia, may also be observed.
Autosomal dominant macrothrombocytopenia (ORPHA:140957)
A rare isolated constitutional thrombocytopenia characterized by abnormally large platelets.
Epidemiology
To date less than 10 cases are reported.
Clinical description
Autosomal dominant macrothrombocytopenia is caused by mutations in the integrin, beta 3 ITGB3, tubulin, beta-1TUBB1 and actinin, alpha1 ACTN1 genes. These mutations lead to abnormal proplatelets and thrombocytopenia.
Etiology
Transmission is autosomal dominant.

                            Last update: 
                            May 2013
Autosomal dominant mendelian susceptibility to mycobacterial diseases due to a partial deficiency (ORPHA:319543)
A group of variants of mendelian susceptibility to mycobacterial diseases (MSMD) due to dominantly inherited partial deficiencies in interferon gamma receptor 1 (IFN-gammaR1), IFN-gammaR2, signal transducer and activator of transcription 1 (STAT1) or interferon regulator factor 8 (IRF8).
Epidemiology
Prevalence is unknown.
Clinical description
The clinical disease seen in all of these variants is relatively mild. Weakly virulent bacillus Calmette-Guérin (BCG) and Mycobacterium avium complex infections are most commonly seen in patients with these diseases.
Etiology
AD MSMD due to a partial deficiency is caused by a mutation in one of the following genes: IFNGR1, IFNGR2, STAT1 or IRF8, depending on the variant. These mutations affect the IFN-gamma pathway and lead to susceptibility to infections with BCG and other environmental mycobacteria.

                            Last update: 
                            February 2013


                            - Expert reviewer(s): 
                            Dr Jacinta BUSTAMANTE  - Pr Jean-Laurent CASANOVA
Autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency (ORPHA:319581)
A rare, genetic variant of mendelian susceptibility to mycobacterial diseases (MSMD) characterized by a partial deficiency leading to impaired IFN-gamma immunity and, consequently, recurrent, moderately severe infections with bacillus Calmette-Guérin (BCG) and other environmental mycobacteria (EM).
Epidemiology
The prevalence is unknown. Since it was first reported in 1999, more than 70 patients bearing heterozygous mutations in IFNGR1 gene have been reported.
Clinical description
Patients present with moderately severe mycobacterial infections at around the age of 13 years. These infections are recurrent but less severe than those seen in MSMD due to complete IFN-gammaR1 and IFN-gammaR2 deficiencies (see these terms). Infections with Mycobacterium bovis BCG or Mycobacterium avium often lead to multifocal or unifocal osteomyelitis in patients with this variant. Salmonellosis has been reported in 5% of cases and infections with other pathogens such as Histoplasma capsulatum and varicella-zoster virus have also been reported in single patients.
Etiology
AD MSMD due to partial IFN-gammaR1 deficiency is caused by heterozygous mutations in the IFNGR1 gene on chromosome 6q23-q24 that encodes the IFN-gamma receptor ligand binding chain. Microdeletion 818del4 is by far the most common mutation and it corresponds to the first documented hotspot for a microdeletion in the human genome. It leads to the expression of IFN-gamma receptor on the cell surface with no signal transduction and therefore patients only show a partial response to IFN-gamma.
Diagnostic methods
Diagnosis is made by laboratory analysis. Cells of patients show a residual response to IFN-gamma in terms of Stat-1 DNA-binding (GAS-binding activity) and HLA-II induction. Genetic testing reveals mutations in IFNGR1.
Differential diagnosis
Other genetic etiologies of MSMD should be excluded.
Antenatal diagnosis
This immunodeficiency is not severe and antenatal diagnosis is not necessary.
Genetic counseling
Transmission is autosomal dominant and genetic counseling is possible.
Management and treatment
BCG vaccination should be avoided in those with a known mutation in the IFNGR1 gene. Patients should be treated with antibiotics and, if necessary, with recombinant IFN-gamma.

                            Last update: 
                            February 2013


                            - Expert reviewer(s): 
                            Dr Jacinta BUSTAMANTE  - Pr Jean-Laurent CASANOVA
Autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR2 deficiency (ORPHA:319589)
A rare, genetic variant of mendelian susceptibility to mycobacterial diseases (MSMD) characterized by a partial deficiency in IFN-gammaR2, leading to impaired response to IFN-gamma and, consequently, to recurrent, moderately severe infections with bacillus Calmette-Guérin (BCG) and other environmental mycobacteria (EM).
Epidemiology
The prevalence is unknown. It was recently discovered in two patients.
Clinical description
The first reported patient with this deficiency presented with moderate mycobacterial infections secondary to BCG vaccination. She developed no other severe infections. The father of this patient was a heterozygous carrier of the mutation, but remained healthy.
Etiology
AD MSMD due to partial IFN-gammaR2 deficiency is caused by a heterozygous mutation in the IFNGR2 gene on chromosome 21q22.1-22.2 that encodes the IFN-gamma receptor ligand binding chain 2. The 186delC mutation corresponds to the first mutation conferring an AD partial IFN-gammaR2 deficiency.

                            Last update: 
                            February 2013


                            - Expert reviewer(s): 
                            Dr Jacinta BUSTAMANTE  - Pr Jean-Laurent CASANOVA
Autosomal dominant mitochondrial myopathy with exercise intolerance (ORPHA:457050)
A rare mitochondrial oxidative phosphorylation disorder due to nuclear DNA anomalies characterized by onset of slowly progressive proximal lower limb weakness and exercise intolerance in the first decade of life, followed by weakness of neck flexor, shoulder, and distal leg muscles. Facial muscles become involved still later in the disease course. Additional manifestations are restrictive pulmonary function and short stature. Laboratory studies reveal lactic acidemia and increased serum creatine kinase.
Autosomal dominant multiple pterygium syndrome (ORPHA:65743)
A rare distal arthrogryposis syndrome characterized by multiple pterygia (typically involving the neck, axilla and popliteal areas), joint contractures, ptosis, camptodactyly of the hands with hypoplastic flexion creases, vertebral fusions, severe scoliosis and short stature.
Autosomal dominant myoglobinuria (ORPHA:99846)
A rare metabolic myopathy characterized by episodic myalgia with myoglobinuria which is induced by fever, viral or bacterial infection, prolonged exercise or alcohol abuse, and could, on occasion, lead to acute renal failure. Between episodes, patients may be asymptomatic or could present elevated creatine kinase levels and mild muscle weakness. There have been no further descriptions in the literature since 1997.
Autosomal dominant myopia-midfacial retrusion-sensorineural hearing loss-rhizomelic dysplasia syndrome (ORPHA:440354)
A rare primary bone dysplasia characterized by micromelia with rhizomelic shortening, metaphyseal widening of the long bones, brachydactyly, small scapulae, micrognathia and thoracic insufficiency requiring tracheostomy and ventilation, and severe myopia and sensorineural hearing loss. Further dysmorphic craniofacial features include frontal bossing, proptosis, epicanthal folds, short nose, flat nasal bridge, anteverted nares, midfacial retrusion, and cleft palate.
Autosomal dominant neovascular inflammatory vitreoretinopathy (ORPHA:329211)
A rare, genetic, vitreoretinal degeneration characterized by a slowly progressive vitreoretinopathy with onset during the second or third decade of life. The disease initially presents as autoimmune uveitis with reduction in the b-wave on electroretinography, and progresses with development of photoreceptor degeneration, vitreous hemorrhage, cystoid macular edema, retinal neovascularization, intraocular fibrosis, secondary glaucoma, and retinal detachment leading to phthisis and complete blindness.
Autosomal dominant optic atrophy and cataract (ORPHA:67036)
A form of autosomal dominant optic atrophy characterized by an early and bilateral optic atrophy leading to insidious visual loss of variable severity, followed by a late anterior and/or posterior cortical cataract. Additional features include sensorineural hearing loss and neurological signs such as tremor, extrapyramidal rigidity and absence of deep tendon reflexes. It is caused by mutations in the OPA3 gene (19q13.32).
Autosomal dominant optic atrophy and peripheral neuropathy (ORPHA:250932)
A rare form of autosomal dominant optic atrophy (ADOA) characterized by progressive and isolated visual loss in the first decade of life, decreased reflexes in the lower limbs and a mild cerebellar stance.
Autosomal dominant osteopetrosis type 1 (ORPHA:2783)
A rare sclerosing bone disorder characterized by skeletal densification that predominantly involves the cranial vault.
Epidemiology
It is extremely rare, as only 33 cases have been reported in 3 families.
Clinical description
The disease typically has onset in late childhood or adolescence. Clinical signs include chronic bone pain and disorders of the cranial nerves (trigeminal neuralgia, facial palsy, hearing loss). The risk of fracture is not increased and patients show normal or even increased trabecular bone strength. Twenty to forty percent of cases are asymptomatic.
Etiology
The disease is due to a gain-of-function mutation in the LRP5 gene (Low density lipoprotein receptor-related protein 5; 11q12-q13) which results in increased bone formation. Therefore, controversy exists whether Autosomal dominant osteopetrosis type 1 is truly a type of osteopetrosis (which is due to failure of osteoclast development or function) or whether it is more accurately described as a `high bone mass' disease.
Diagnostic methods
Diagnosis is based on clinical and radiographic evaluation. Radiographs show diffuse skeletal sclerosis, with marked thickening of the cranial vault, slight sclerosis of the spine with dense vertebral arches, and thickened long bone cortices. Bone mineral density (lumbar spine, femoral neck) has a Z-score ranging from +4 to +8 SD.
Genetic counseling
Transmission is autosomal dominant. Each child of an affected individual has a 50% risk of being affected. Autosomal dominant osteopetrosis type 1 is a fully penetrant disease.
Management and treatment
Treatment is symptomatic.
Prognosis
Life expectancy is normal.

                            Last update: 
                            March 2010


                            - Expert reviewer(s): 
                            Dr Ravi SAVARIRAYAN  - Dr Zornitza STARK
Autosomal dominant otospondylomegaepiphyseal dysplasia (ORPHA:166100)
A rare, genetic, multiple congenital anomalies/dysmorphic syndrome characterized by craniofacial dysmorphism (midface hypoplasia, depressed nasal bridge, small nose with upturned tip, cleft palate, Pierre Robin sequence), bilateral, pronounced sensorineural hearing loss, and skeletal/joint anomalies (including spondyloepiphyseal dysplasia, arthralgia/arthropathy), in the absence of ocular abnormalities.
Autosomal dominant palmoplantar keratoderma and congenital alopecia (ORPHA:1010)
A rare genetic skin disorder characterized by absence of scalp and body hair and palmoplantar keratoderma, without other hand complications.
Epidemiology
To date, ten individuals with a clinical diagnosis of autosomal dominant palmoplantar keratoderma and congenital alopecia (PPK-CA) have been reported.
Clinical description
Autosomal dominant PPK-CA usually presents during infancy. Its very early onset is often characterized by fading of facial, scalp and body hair within the first months of life without subsequent re-growth. Body and facial keratosis pilaris are additional features which appear in the following years. Palmoplantar keratoderma develops during infancy and may have an unusual pattern, affecting the two sides of fingers and palms, but usually sparing the palmar sides. Periungueal involvement is typical, leading to secondary nail dystrophy. Autosomal dominant PPK-CA seems to have a more benign course than autosomal recessive PPK-CA (see this term).
Etiology
The genetic basis of autosomal dominant PPK-CA is unknown. Transmission appears to be autosomal dominant.
Differential diagnosis
Palmoplantar keratoderma and congenital alopecia/hypotrichosis is also found in ectodermal dysplasias and keratinization disorders, including hydrotic ectodermal dysplasia; hypotrichosis-osteolysis-periodontitis-palmoplantar keratoderma syndrome; KID syndrome; odonto-onycho-dermal dysplasia; Lelis syndrome; mutilating palmoplantar keratoderma with periorificial keratotic plaques; and Schöpf-Schulz-Passarge syndrome.
Genetic counseling
Transmission appears to be autosomal dominant.

                            Last update: 
                            July 2013


                            - Expert reviewer(s): 
                            Dr Marco CASTORI
Autosomal dominant polycystic kidney disease type 1 with tuberous sclerosis (ORPHA:88924)
A rare contiguous gene syndrome involving a partial deletion of chromosome 16 and characterized by early-onset and severe polycystic kidney disease with various manifestations of tuberous sclerosis (multiple angiomyolipomas, lymphangioleiomyomatosis and periventricular calcifications of the central nervous system).