TaoMedAI/RareMedData huggingface dataset:
Autosomal dominant preaxial polydactyly-upperback hypertrichosis syndrome (ORPHA:476119)
A rare genetic syndrome with limb malformations as a major feature characterized by preaxial polydactyly of the hands and feet with variable phenotypic expressivity in combination with hypertrichosis extending from the posterior hairline to the middle of the back. Reported limb malformations include triphalangeal thumbs, duplicated thumbs, preaxial extra ray, and syndactyly between digits I and II in the hands, and large or duplicated hallux and syndactyly between toes I and II in the feet.
Autosomal dominant primary hypomagnesemia with hypocalciuria (ORPHA:34528)
A mild form of familial primary hypomagnesemia (FPH), characterized by extreme weakness, tetany and convulsions. Secondary disturbances in calcium excretion are observed.
Epidemiology
To date, only one large pedigree with 18 affected individuals has been reported in the literature.
Clinical description
Autosomal dominant primary hypomagnesemia with hypocalciuria (ADPHH) can be detected in childhood or in adult life. Most affected individuals are asymptomatic but patients may suffer from generalized convulsions. In adulthood, chondrocalcinosis may be observed.
Differential diagnosis
Differential diagnosis includes all causes of renal hypomagnesemia, particularly diseases associated with hypocalciuria such as Gitelman syndrome, EAST syndrome and familial primary hypomagnesemia with normocalciuria and normocalcemia (see these terms).
Genetic counseling
Transmission is autosomal dominant. Genetic counseling may be proposed and the recurrence risk is 50%.
Management and treatment
Management is mainly symptomatic and includes oral magnesium supplements.

                            Last update: 
                            February 2014


                            - Expert reviewer(s): 
                            Dr Rosa VARGAS-POUSSOU
Autosomal dominant primary microcephaly (ORPHA:2514)
A rare, genetic, non-syndromic, developmental defect during embryogenesis malformation syndrome characterized by a congenital, non-progressive, occipitofrontal head circumference that is 2 or more standard deviations below the mean for age, gender and ethnicity which is associated with normal brain architecture and uncomplicated by other abnormalities. Borderline to moderate intellectual disability, as well as early psychomotor delay, may or may not be associated.
Autosomal dominant prognathism (ORPHA:2964)
A rare, genetic, developmental defect during embryogenesis disorder characterized by abnormal forward projection of the mandible beyond the standard relation to the cranial base, with lower incisors often overlapping the upper incisors, that is inherited in an autosomal dominant manner. Association with mildly everted lower eyelids, flat malar area, thickened lower lip and craniosynostosis has been reported.
Autosomal dominant progressive external ophthalmoplegia (ORPHA:254892)
A rare genetic, neuro-ophthalmological disease characterized by progressive weakness of the external eye muscles, resulting in bilateral ptosis and diffuse symmetric ophthalmoparesis. Additional signs may include skeletal muscle weakness, cataracts, hearing loss, sensory axonal neuropathy, ataxia, parkinsonism, cardiomyopathy, hypogonadism and depression. It is usually less severe than autosomal recessive form.
Autosomal dominant progressive nephropathy with hypertension (ORPHA:88659)
A rare, genetic hypertension characterized by an adult onset of increased blood pressure associated with nephropathy progressing to end-stage renal disease. Renal biopsy may show interstitial fibrosis, glomerulosclerosis and mild tubular atrophy. Increased serum creatinine and proteinuria have also been reported.
Autosomal dominant proximal renal tubular acidosis (ORPHA:314889)
A rare autosomal dominant form of proximal renal tubular acidosis (pRTA) characterized by an isolated defect in the proximal tubule leading to the decreased reabsorption of bicarbonate and consequently causing urinary bicarbonate wastage. Mild growth retardation and reduced bone density are extra-renal complications. Several fractures and delayed puberty are possible features.
Autosomal dominant proximal spinal muscular atrophy (ORPHA:211037)
A group of rare, genetic, motor neuron disease characterized by childhood or adult onset progressive, predominantly proximal, muscular weakness and wasting. Included diseases are Autosomal dominant adult-onset proximal spinal muscular atrophy, Lower motor neuron syndrome with late-adult onset, and Autosomal dominant childhood-onset proximal spinal muscular atrophy.
Autosomal dominant rhegmatogenous retinal detachment (ORPHA:209867)
A rare, hereditary, non-syndromic form of vitreoretinopathy characterized by retinal tears due to abnormal vitreous, and commonly present refractive errors. No other signs or symptoms of Stickler syndrome is present.
Autosomal dominant Robinow syndrome (ORPHA:3107)
The more common type of Robinow syndrome (RS) characterized by mild to moderate limb shortening and abnormalities of the head, face and external genitalia.
Epidemiology
About 100 cases of this type have been reported in the literature to date.
Clinical description
The clinical signs are generally milder in dominant cases of RS than in the AR form. In the presence of rib fusions, the recessive form of the syndrome should be considered.
Etiology
Mutations in WNT5A gene (3p14.3) have been reported in some patients (< 10%) with autosomal dominant Robinow syndrome.
Genetic counseling
Transmission is autosomal dominant.

                            Last update: 
                            May 2011


                            - Expert reviewer(s): 
                            Dr Juliana MAZZEU
Autosomal dominant secondary polycythemia (ORPHA:247511)
A rare, genetic, hematologic disease characterized by increased levels of serum hemoglobin, hematocrit and erythrocyte mass, associated with elevated or inappropriately normal erythropoietin serum levels, occurring in various members of a family and with autosomal dominant inheritance.
Autosomal dominant severe congenital neutropenia (ORPHA:486)
A rare primary immunodeficiency disorder characterized by autosomal dominant inheritance, absolute neutrophil counts below 0.5x10E9/L in the peripheral blood (on three separate occasions over a six month period), granulopoiesis maturation arrest at the promyelocyte/myelocyte stage and early-onset, severe, recurrent bacterial infections.
Autosomal dominant slowed nerve conduction velocity (ORPHA:140481)
A rare hereditary demyelinating motor and sensory neuropathy characterized by slowed nerve conduction velocities, in the absence of clinically apparent neurological deficits, gait abnormalities or muscular atrophy, associated with a germline mutation in the ARGHEF10 gene.
Autosomal dominant spastic ataxia type 1 (ORPHA:251282)
A rare, genetic, autosomal dominant spastic ataxia disorder characterized by lower-limb spasticity and ataxia in the form of head jerks, ocular movement abnormalities, dysarthria, dysphagia and gait disturbances.
Autosomal dominant spastic paraplegia type 10 (ORPHA:100991)
A rare, hereditary spastic paraplegia that can present as either a pure or complex phenotype. The pure form is characterized by lower limb spasticity, hyperreflexia and extensor plantar responses, presenting in childhood or adolescence. The complex form is characterized by the association with additional manifestations including peripheral neuropathy with upper limb muscle atrophy, moderate intellectual disability and parkinsonism. Deafness and retinitis pigmentosa have also been reported.
Autosomal dominant spastic paraplegia type 12 (ORPHA:100993)
A pure form of hereditary spastic paraplegia characterized by a childhood- to adulthood-onset of slowly progressive lower limb spasticity and hyperreflexia of lower extremities, extensor plantar reflexes, distal sensory impairment, variable urinary dysfunction and pes cavus.
Autosomal dominant spastic paraplegia type 13 (ORPHA:100994)
A rare, pure or complex form of hereditary spastic paraplegia characterized by progressive spastic paraplegia with pyramidal signs in the upper and lower limbs, and decreased vibration sense.
Autosomal dominant spastic paraplegia type 17 (ORPHA:100998)
A complex hereditary spastic paraplegia characterized by progressive spastic paraplegia, upper and lower limb muscle atrophy, hyperreflexia, extensor plantar responses, pes cavus and occasionally impaired vibration sense. Association with hand muscles amyotrophy typical.
Autosomal dominant spastic paraplegia type 19 (ORPHA:100999)
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.
Autosomal dominant spastic paraplegia type 29 (ORPHA:101009)
A complex form of hereditary spastic paraplegia characterized by a spastic paraplegia presenting in adolescence, associated with the additional manifestations of sensorial hearing impairment due to auditory neuropathy and persistent vomiting due to a hiatal or paraesophageal hernia.
Autosomal dominant spastic paraplegia type 3 (ORPHA:100984)
A rare, pure or complex form of hereditary spastic paraplegia, with variable phenotype, typically characterized by childhood-onset of minimally progressive, bilateral, mainly symmetric lower limb spasticity and weakness, associated with pes cavus, scoliosis, sphincter disturbances and/or urinary bladder hyperactivity. Rare additional associated manifestations may include mild intellectual disability, axonal motor neuropathy, and seizures.
Autosomal dominant spastic paraplegia type 31 (ORPHA:101011)
A rare type of hereditary spastic paraplegia usually characterized by a pure phenotype of proximal weakness of the lower extremities with spastic gait and brisk reflexes, with a bimodal age of onset of either childhood or adulthood (>30 years). In some cases, it can present as a complex phenotype with additional associated manifestations including peripheral neuropathy, bulbar palsy (with dysarthria and dysphagia), distal amyotrophy, and impaired distal vibration sense.
Autosomal dominant spastic paraplegia type 36 (ORPHA:320365)
A complex form of hereditary spastic paraplegia, characterized by an onset in childhood or adulthood of progressive spastic paraplegia (with spastic gait, spasticity, lower limb weakness, pes cavus and urinary urgency) associated with the additional manifestation of peripheral sensorimotor neuropathy.
Autosomal dominant spastic paraplegia type 37 (ORPHA:171612)
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.
Autosomal dominant spastic paraplegia type 38 (ORPHA:171617)
A complex hereditary spastic paraplegia characterized by mild to severe lower limb spasticity, hyperreflexia, extensor plantar responses, impaired vibration sensation, pes cavus, and significant wasting and weakness of the small hand muscles. Temporal lobe epilepsy and cognitive dysfunction have been also reported.
Autosomal dominant spastic paraplegia type 4 (ORPHA:100985)
A rare form of hereditary spastic paraplegia with high intrafamilial clinical variability, characterized in most cases as a pure phenotype with an adult onset (mainly the 3rd to 5th decade of life, but that can present at any age) of progressive gait impairment due to bilateral lower-limb spasticity and weakness as well as very mild proximal weakness and urinary urgency. In some cases, a complex phenotype is also reported with additional manifestations including cognitive impairment, cerebellar ataxia, epilepsy and neuropathy. A faster disease progression is noted in patients with a later age of onset.
Autosomal dominant spastic paraplegia type 41 (ORPHA:320355)
A pure form of hereditary spastic paraplegia characterized by onset in adolescence or early adulthood of slowly progressive spastic paraplegia, proximal muscle weakness of the lower extremities and small hand muscles, hyperreflexia, spastic gait and mild urinary compromise.
Autosomal dominant spastic paraplegia type 42 (ORPHA:171863)
A pure form of hereditary spastic paraplegia characterized by slowly progressive spastic paraplegia of lower extremities with an age of onset ranging from childhood to adulthood and patients presenting with spastic gait, increased tendon reflexes in lower limbs, extensor plantar response, weakness and atrophy of lower limb muscles and, in rare cases, pes cavus. No abnormalities are noted on magnetic resonance imaging.
Autosomal dominant spastic paraplegia type 6 (ORPHA:100988)
A rare, pure or complex form of hereditary spastic paraplegia typically characterized by presentation in late adolescence or early adulthood as a pure phenotype of lower limb spasticity with hyperreflexia and extensor plantar responses, as well as mild bladder disturbances and pes cavus. Rarely, it can present as a complex phenotype with additional manifestations including epilepsy, variable peripheral neuropathy and/or memory impairment.
Autosomal dominant spastic paraplegia type 73 (ORPHA:444099)
A pure form of hereditary spastic paraplegia characterized by adult onset of crural spastic paraparesis, hyperreflexia, extensor plantar responses, proximal muscle weakness, mild muscle atrophy, decreased vibration sensation at ankles, and mild urinary dysfunction. Foot deformities have been reported to eventually occur in some patients. No abnormalities are noted on brain magnetic resonance imaging and peripheral nerve conduction velocity studies.
Autosomal dominant spastic paraplegia type 8 (ORPHA:100989)
A rare, pure or complex form of hereditary spastic paraplegia characterized by early adulthood onset of slowly progressive lower limb spasticity resulting in gait disturbances, hyperreflexia and extensor plantar responses, urinary urgency and/or incontinence, muscle weakness, decreased vibration sense and mild muscular atrophy in lower extremities. It may be associated with complicating signs, such as sensory neuropathy, ataxia (i.e. mild dysmetria, uncoordinated eye movement) and mild dysphagia.
Autosomal dominant spastic paraplegia type 9A (ORPHA:447753)
A rare complex hereditary spastic paraplegia characterized by juvenile to adult onset of slowly progressive spasticity mainly affecting the lower limbs, associated with spastic dysarthria and motor neuropathy. Additional manifestations include congenital bilateral cataract, gastroesophageal reflux, persistent vomiting, mild cerebellar signs, pes cavus, and occasionally short stature, among others.
Autosomal dominant spastic paraplegia type 9B (ORPHA:447757)
A rare predominantly pure hereditary spastic paraplegia characterized by juvenile or adult onset of slowly progressive spastic paraparesis, gait disturbances, and increased tendon reflexes. Additional variable manifestations include pes cavus, dysarthria, sensory impairment, and urinary symptoms. Cognition is normal.
Autosomal dominant spondylocostal dysostosis (ORPHA:1797)
A very rare and mild form of spondylocostal dysostosis characterized by vertebral and costal segmentation defects, often with a reduction in the number of ribs.
Autosomal dominant striatal neurodegeneration (ORPHA:228169)
An adult-onset movement disorder characterized by bradykinesia, dysarthria and muscle rigidity.
Epidemiology
To date, ADSD has been observed in seven individuals in one family.
Clinical description
Onset of symptoms of ADSD is in the fourth to fifth decade of life with mild progressive dysarthria and hypokinesia. Mild bradykinesia presents predominantly as gait disturbance but also as a general slowing of movement. Dysdiadochokinesia is also present and muscle tone is slightly increased. Additional features include stiffness of the tongue and, in some patients, mild difficulties in swallowing. ADSD is characterized by dysfunction and changes of the striatal part of the basal ganglia, visible on MRI scans.
Etiology
It is caused by mutation in the PDE8B gene (5q13.3-q14.1) and is transmitted in an autosomal dominant manner with complete penetrance in the investigated family.
Diagnostic methods
Diagnosis is based on brain MRI which shows distinctive and characteristic symmetric lesions of the striatum that appear earlier than the onset of symptoms. A good correlation has been observed between clinical signs and the degree of MRI abnormalities.
Differential diagnosis
Differential diagnoses include other degenerative diseases causing hypokinesia (such as Parkinson's disease; see this term). However, unlike for these diseases, in ADSD, tremor is not observed. Differential diagnoses also include neuroferritinopathy (see this term). However, ADSD is characterized by hypokinesia whereas neuroferritinopathy is characterized by hyperkinesia. The characteristic MRI changes of the striatum can be regarded as pathognomonic for ADSD.
Antenatal diagnosis
Antenatal diagnosis is currently not available but is probably not necessary because of the mild course of the disease.
Management and treatment
There is currently no known treatment for ADSD and symptoms do not respond to treatment with levodopa.
Prognosis
The course of the disease is mild and allows affected individuals to lead a virtually normal life. Life expectancy does not appear to be affected.

                            Last update: 
                            May 2010


                            - Expert reviewer(s): 
                            Pr Gregor KUHLENBÄUMER
Autosomal dominant thrombocytopenia with platelet secretion defect (ORPHA:466806)
A rare isolated constitutional thrombocytopenia characterized by reduced platelet count and defective platelet ATP secretion, resulting in increased bleeding tendency. Clinical manifestations are easy bruising, gum bleeding, menorrhagia, spontaneous epistaxis, spontaneous muscle hematoma, and potential postpartum hemorrhage, among others.
Autosomal recessive anterior segment dysgenesis (ORPHA:519388)
A rare anterior segment developmental anomaly without extraocular manifestations characterized by predominant iris and lens abnormalities, including iris hypoplasia, iris transillumination defects, ectropion uveae, corectopia, iridodonesis with ectopia lentis, and cataracts, with bilateral involvement. Increased intraocular pressure is absent in most patients.
Autosomal recessive ataxia due to PEX10 deficiency (ORPHA:247815)
A rare genetic, peroxisomal disease characterized by childhood onset slowly progressive ataxia and axonal motor neuropathy due to PEX 10 deficieny. Marked cerebellar atrophy and pyramidal signs are evident. Patients may present mild cognitive disability, intentional tremor, decreased vibration sense and diabetes mellitus. Additional features may include nystagmus, mydriasis, hyperreflexia and involuntary head movement.
Autosomal recessive ataxia due to ubiquinone deficiency (ORPHA:139485)
This syndrome is characterised by childhood-onset progressive ataxia and cerebellar atrophy.
Epidemiology
Prevalence is unknown.
Clinical description
Exercise intolerance with elevated lactate levels and mild intellectual deficit may also be present.
Etiology
The syndrome is caused by ubiquinone deficiency. Mutations in the ADCK3/CABC1 gene have been detected in affected individuals. This gene is already known to play a role in ubiquinone biosynthesis in yeast.
Genetic counseling
The syndrome is transmitted as an autosomal recessive trait.

                            Last update: 
                            May 2008
Autosomal recessive ataxia, Beauce type (ORPHA:88644)
A rare disorder characterised by a slowly progressive pure cerebellar ataxia associated with dysarthria. It has been described in 53 individuals from 26 families of Canadian origin. The mode of transmission is autosomal recessive. Positional cloning has led to the identification of several  gene mutations.
Autosomal recessive axonal Charcot-Marie-Tooth disease due to copper metabolism defect (ORPHA:521411)
A rare autosomal recessive axonal hereditary motor and sensory neuropathy characterized by motor-predominant axonal polyneuropathy due to a defect in copper metabolism. Patients become symptomatic in infancy or childhood with subtle motor delay or regression, manifesting with progressive weakness, muscle wasting, and absent reflexes in the lower and upper extremities. In addition, vibratory sensation is mildly diminished. Involvement of the face with weakness and fasciculation of facial muscles has also been described.
Autosomal recessive axonal neuropathy with neuromyotonia (ORPHA:324442)
A rare peripheral neuropathy characterized by slowly progressive axonal, motor greater than sensory, polyneuropathy combined with neuromytonia (including spontaneous muscular activity at rest (myokymia), impaired muscle relaxation (pseudomyotonia), and contractures of hands and feet) and neuromyotonic or myokymic discharges on needle EMG. It presents with distal lower limb weakness with gait impairment, muscle stiffness, fasciculations and cramps in hands and legs worsened by cold, decreased to absent tendon reflexes, intrinsic hand muscle atrophy and, variably, mild distal sensory impairment.
Autosomal recessive brachyolmia (ORPHA:448242)
Brachyolmia, recessive type is a form of brachyolmia (see this term), 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.
Epidemiology
The precise prevalence of this form of brachyolmia is not known. About 20 cases have been reported. Cases have been reported in various ethnic groups (Japan, Korea, Turkey), sometimes related to consanguineous unions. However, a majority of cases reported so far were of Turkish origin.
Clinical description
Patients with Brachyolmia, recessive type generally have a normal birth weight and length. Platyspondyly is present in early childhood but patients usually come to medical attention in late childhood or early puberty as a result of stunted growth and short trunk. The radiographic features include platyspondyly with rectangular vertebral bodies and irregular end plates, broad ilia, short femoral neck, and broad proximal interphalangeal joints. Longitudinal striations in the femoral neck are occasionally seen. Precocious calcifications of the costal cartilage are described. The condition is described as relatively benign with the exception of mild non-specific backache and mild scoliosis beginning in young adulthood. However, reports are limited about the final outcome of musculoskeletal morbidity. Mental status and facies are reported to be normal. Some patients are reported to have peripheral punctuate opacities in the cornea found on slit lamp examination (formerly Toledo type).
Etiology
A number of different mutations in the PAPSS2 gene (10q23.2-q23.3) have been reported in affected patients. PAPPS2 encodes PAPS (3'-phosphoadenosine 5'-phosphosulfate) synthase 2. PAPSS2 mutations were also reported to cause two other disorders: spondyloepimetaphyseal dysplasia, PAPSS2 type (see this term), and spondylodysplasia and premature pubarche before the discovery of the molecular basis of brachyolmia, recessive type (Hobaek/Toledo type).
Genetic counseling
Genetic counseling should be provided to affected families based on the observed autosomal recessive pattern of inheritance.

                            Last update: 
                            February 2016


                            - Expert reviewer(s): 
                            Dr Gen NISHIMURA