TaoMedAI/RareMedData huggingface dataset:
Autosomal recessive centronuclear myopathy (ORPHA:169186)
A rare autosomal recessive congenital myopathy characterized by numerous centrally placed nuclei on muscle biopsy and clinical features of a congenital myopathy including facial weakness, ocular abnormalities (ptosis and external ophthalmoplegia) and predominant proximal muscle weakness of variable severity with possible distal involvement.
Epidemiology
The exact prevalence remains unknown.
Clinical description
The age of onset varies from birth to childhood. AR-CNM is characterized by facial weakness including severe involvement of the masticatory muscles, and ocular abnormalities such as ptosis and external ophthalmoplegia. Muscle weakness is observed with variable severity. It is usually prominently proximal, but there may be additional distal weakness and wasting in the lower limbs. Foot abnormalities are frequent and other skeletal deformities (including high arched palate and scoliosis) are common. Respiratory involvement may be severe. An associated cardiomyopathy has been documented in a few, genetically unresolved cases. Urinary incontinence may be an associated feature.
Etiology
The disease is associated with mutations in BIN1 (2q14), encoding Myc box-dependent-interacting protein 1. AR- CNMs can be also related to biallelic mutation in RYR1 (19q13.2) , SPEG (2q35) and TTN (2q31.2) genes.
Diagnostic methods
Diagnosis is based on typical histopathological findings on muscle biopsy in combination with suggestive clinical features. Genetic testing is required to confirm the diagnosis. Muscle MRI may be helpful to distinguish AR-CNM from other forms of CNM.
Differential diagnosis
The main differential diagnoses include other congenital myopathies, myotonic dystrophy and, if facial involvement is prominent, facioscapulohumeral dystrophy.
Antenatal diagnosis
Prenatal diagnosis is possible where the mutation has previously been identified in a family member.
Genetic counseling
The pattern of inheritance is autosomal recessive. The risk to siblings of inheriting the disease is 25%. Offspring of affected individuals are obligate carriers. Genetic counseling should be offered to all patients and their families.
Management and treatment
There is no curative treatment currently available. Management is supportive and based on a multidisciplinary approach.
Prognosis
In the absence of severe cardiorespiratory involvement, the prognosis appears favorable, with mild progressive proximal weakness.

                            Last update: 
                            May 2020


                            - Expert reviewer(s): 
                            Pr Enrico BERTINI  - Dr Adele D'AMICO  - Pr Fabiana FATTORI
Autosomal recessive cerebellar ataxia due to CWF19L1 deficiency (ORPHA:453521)
A rare autosomal recessive cerebellar ataxia characterized by early onset of slowly progressive cerebellar atrophy, clinically manifesting with extremity and truncal ataxia, global developmental delay, intellectual impairment, nystagmus, dysarthria, intention tremor, and pyramidal signs, among others.
Autosomal recessive cerebellar ataxia due to STUB1 deficiency (ORPHA:412057)
A rare hereditary ataxia characterized by progressive truncal and limb ataxia resulting in gait instability. Dysarthria, dysphagia, nystagmus, spasticity of the lower limbs, mild peripheral sensory neuropathy, cognitive impairment and accelerated ageing have also been associated.
Autosomal recessive cerebellar ataxia with late-onset spasticity (ORPHA:352641)
A rare, genetic neurodegenerative disease characterized by childhood or adolescent-onset of cerebellar ataxia with dysarthria which slowly progresses and associates pyramidal signs, including lower limb spasticity, brisk reflexes, and Babinski and Hoffman signs. Patients typically present cerebellar ataxia with development of increasing asymmetric spasticity in upper and lower limbs, and variable axonal sensory or sensorimotor neuropathy. Additional heterogeneous features, including pes cavus, scoliolis, and abnormalities of the brain (e.g. cerebral atrophy), may also be associated.
Autosomal recessive cerebellar ataxia-epilepsy-intellectual disability syndrome due to RUBCN deficiency (ORPHA:404499)
An extremely rare, autosomal recessive, hereditary cerebellar ataxia disorder characterized by early onset of progressive, mild to moderate gait and limb ataxia, moderate to severe dysarthria, and nystagmus or saccadic pursuit, frequently associated with epilepsy, moderate intellectual disability, delayed speech acquisition, and hyporeflexia in the upper extremities. Hyperreflexia in the lower extremities may also be associated.
Autosomal recessive cerebellar ataxia-epilepsy-intellectual disability syndrome due to TUD deficiency (ORPHA:404493)
A rare hereditary ataxia characterized by an early onset symptomatic generalized epilepsy, progressive cerebellar ataxia resulting in significant difficulties to walk or wheelchair dependency, and intellectual disability.
Autosomal recessive cerebellar ataxia-epilepsy-intellectual disability syndrome due to WWOX deficiency (ORPHA:284282)
A rare autosomal recessive cerebellar ataxia-epilepsy-intellectual disability syndrome characterized by early-childhood onset of cerebellar ataxia associated with generalized tonic-clonic epilepsy and psychomotor development delay, dysarthria, gaze-evoked nystagmus and learning disability. Other features in some patients include upper motor neuron signs with leg spasticity and extensor plantar responses, and mild cerebellar atrophy on brain MRI.
Autosomal recessive cerebellar ataxia-movement disorder syndrome (ORPHA:95434)
A rare hereditary ataxia characterized by a progressive cerebellar ataxia associated with disruption of visual fixation by saccadic intrusions (overshooting horizontal saccades with macrosaccadic oscillations and increased velocity of larger saccades). It presents with progressive gait, trunk and limb ataxia with pyramidal tract signs (increased tendon reflexes and Babinski sign), myoclonic jerks, fasciculations, cerebellar dysarthria, sensorimotor axonal neuropathy with impaired joint position, vibration, temperature, pain sensations, pes cavus, and saccadic intrusions with characteristic overshooting horizontal saccades, macrosaccadic oscillations, and increased velocity of larger saccades, without other eye movement disturbances.
Autosomal recessive cerebellar ataxia-psychomotor delay syndrome (ORPHA:284271)
A rare, hereditary, cerebellar ataxia disorder characterized by late-onset spinocerebellar ataxia, manifesting with slowly progressive gait disturbances, dysarthria, limb and truncal ataxia, and smooth-pursuit eye movement disturbance, associated with a history of psychomotor delay from childhood. Mild atrophy of the cerebellar vermis and hemispheres is observed on brain imaging.
Autosomal recessive cerebellar ataxia-pyramidal signs-nystagmus-oculomotor apraxia syndrome (ORPHA:363429)
A rare, genetic, slowly progressive neurodegenerative disease characterized by delayed psychomotor development beginning in infancy, mild to profound intellectual disability, gait and stance ataxia, pyramidal signs (hyperreflexia, extensor plantar responses), dysarthria, and ocular abnormalities (e.g. nystagmus, oculomotor apraxia, abduction deficits, esotropia, ptosis). Brain imaging reveals progressive, generalized cerebellar atrophy, mild ventriculomegaly and, in some, retrocerebellar cysts.
Autosomal recessive cerebellar ataxia (ORPHA:1172)
A heterogeneous group of rare neurological disorders involving both the central and peripheral nervous system (and in some cases other systems and organs), and characterized by degeneration or abnormal development of the cerebellum and spinal cord and, in most cases, early onset occurring before the age of 20 years.
Epidemiology
This group encompasses a large number of rare diseases, the most frequent in the Caucasian population being Friedreich ataxia (estimated prevalence 2-4/100,000), ataxia-telangiectasia (1-2.5/100,000) and early onset cerebellar ataxia with retained tendon reflexes (1/100,000). Other forms ARCA are much less common.
Clinical description
Based on clinicogenetic criteria, five main types ARCA can be distinguished: congenital ataxias (developmental disorders), ataxias associated with metabolic disorders, ataxias with a DNA repair defect, degenerative ataxias, and ataxia associated with other features.
Etiology
These diseases are caused by mutations in specific genes, some of which have been identified, such as frataxin in Friedreich ataxia, alpha-tocopherol transfer protein in ataxia with vitamin E deficiency (AVED), aprataxin in ataxia with oculomotor apraxia (AOA1), and senataxin in ataxia with oculomotor apraxia (AOA2).
Diagnostic methods
Clinical diagnosis is confirmed by ancillary tests such as neuroimaging (magnetic resonance imaging, computed tomography scanning), electrophysiological examination, and mutation analysis when the causative gene has been identified. Correct clinical and genetic diagnosis is important for appropriate genetic counseling and prognosis and, in some instances, pharmacological treatment. Due to the autosomal recessive mode of inheritance, a familial history of affected individuals is unlikely.
Genetic counseling
These diseases are transmitted in an autosomal recessive manner.
Management and treatment
For most ARCA there is no specific drug treatment, except for coenzyme Q10 deficiency and abetalipoproteinemia.

                            Last update: 
                            November 2006


                            - Expert reviewer(s): 
                            Dr Carmen ESPINÓS  - Pr Francesc PALAU
Autosomal recessive cerebelloparenchymal disorder type 3 (ORPHA:1170)
A rare autosomal recessive cerebellar ataxia characterized by early onset of non- or slowly progressive cerebellar signs and symptoms including truncal and gait ataxia, dysarthria, dysmetria, dysdiadochokinesis, tremor, and nystagmus. Delayed psychomotor development and intellectual disability are variable. Additional reported features are spasticity, hypotonia, cataracts, and sensorineural hearing loss, among others. Brain imaging shows cerebellar atrophy.
Autosomal recessive cerebral atrophy (ORPHA:363969)
A rare, genetic, neurodegenerative disorder characterized by ventriculomegaly and progressive, symmetrical atrophy of the cerebral cortex grey and white matter (sparing the midbrain, brainstem, cerebellum and infratentorial segments), manifesting in early infancy with acquired microcephaly, irritability, regression of developmental milestones, feeding difficulties, akathisia, exaggerated startle response, spasticity (fisted hands, stiff arms, leg scissoring), abnormal muscle tone with hypotonic trunk and hypertonic extremities, visual impairment and seizures.
Autosomal recessive Charcot-Marie-Tooth disease type 2X (ORPHA:466775)
A rare autosomal recessive axonal hereditary motor and sensory neuropathy characterized by childhood to adult onset of slowly progressive, sometimes asymmetric distal muscle weakness and atrophy, as well as sensory impairment, predominantly of the lower limbs. Additional common features include pes cavus, kyphoscoliosis, ankle contractures, tremor, or urogenital dysfunction. Fasciculations and proximal involvement may be seen in some cases. Patients usually remain ambulatory.
Autosomal recessive Charcot-Marie-Tooth disease with hoarseness (ORPHA:101097)
A severe, early-onset form of axonal CMT peripheral sensorimotor polyneuropathy.
Epidemiology
ARCMT2K was originally described in three Spanish families and has since been described in five additional Spanish kindreds, as well as in families from Morocco, France and Poland.
Clinical description
Onset occurs in the neonatal period or early infancy with a clinical picture similar to that seen in CMT4A (another autosomal recessive form of CMT4 but with a demyelinating phenotype; see this term) including hypotonia, scoliosis, a hoarse voice, vocal cord paralysis and respiratory insufficiency. However, nerve conduction velocities and pathological findings from sural nerve biopsies in ARCMT2K patients are indicative of a predominantly axonal neuropathy with some demyelinating features.
Etiology
ARCMT2K is caused by mutations in the GDAP1 gene (8q13.3), encoding a protein required for mitochondrial fission. Mutations in the same gene are associated with CMT4A and with a milder, later-onset autosomal dominant axonal form of CMT, CMT2K (see this term).
Prognosis
The prognosis for ARCMT2K may be severe, with two of the reported patients dying during in the fifth decade of life.

                            Last update: 
                            January 2009


                            - Expert reviewer(s): 
                            Dr Carmen ESPINÓS  - Pr Francesc PALAU
Autosomal recessive chorioretinopathy-microcephaly syndrome (ORPHA:2518)
A rare neuro-opthalmological disease characterized by severe microcephaly of prenatal onset (with diminutive anterior fontanelle and sutural ridging), growth retardation, global developmental delay and intellectual disability (ranging from mild to profound), dysmorphic features (sloping forehead, micro/retrognathia, prominent ears) and visual impairments (including microphthalmia to anophtalmia, generalized retinopathy or multiple punched-out retinal lesions, retinal folds with retinal detachment, optic nerve hypoplasia, strabismus, nystagmus). Brain MRI may show reduced cortical size, cerebral hemispheres, corpus callosum, pachygyria, symplified gyral folding or normal pattern. Other associated features include epilepsy and neurological deficits.
Autosomal recessive complex spastic paraplegia due to Kennedy pathway dysfunction (ORPHA:506353)
A rare genetic neurological disorder characterized by progressive spastic paraparesis and delayed gross motor development with an onset in infancy or early childhood. Patients also show variable degrees of intellectual disability, speech delay, and dysarthria. Other reported features include microcephaly, seizures, bifid uvula with or without cleft palate, and ocular anomalies. Brain imaging shows white matter abnormalities in the periventricular and other regions.
Autosomal recessive congenital cerebellar ataxia due to GRID2 deficiency (ORPHA:363432)
A rare, genetic, slowly progressive neurodegenerative disease resulting from GRID2 deficiency characterized by motor, speech and cognitive delay, hypotonia, truncal and appendicular ataxia, and eye movement abnormalities (tonic upgaze, nystagmus, oculomotor apraxia). Intention tremor may also be associated. Brain imaging reveals progressive cerebellar atrophy with cerebellar flocculus particularly affected.
Autosomal recessive congenital cerebellar ataxia due to MGLUR1 deficiency (ORPHA:324262)
A rare, genetic, slowly progressive neurodegenerative disease resulting from MGLUR1 deficiency characterized by global developmental delay (beginning in infancy), mild to severe intellectual deficit with poor or absent speech, moderate to severe stance and gait ataxia, pyramidal signs (e.g. hyperreflexia) and mild dysdiadochokinesia, dysmetria, tremors, and/or dysarthria. Oculomotor signs, such as nystagmus, strabismus, ptosis and hypometric saccades, may also be associated. Brain imaging reveals progressive, generalized, moderate to severe cerebellar atrophy, inferior vermian hypoplasia, and/or constitutionally small brain.
Autosomal recessive cutis laxa type 2A (ORPHA:357058)
A rare, genetic, dermis elastic tissue disease characterized by redundant, overfolded skin of variable severity, ranging from wrinkly skin to cutis laxa associated with pre- and post-natal growth retardation, hypotonia, mild to moderate developmental delay, late closure of anterior fontanelle, and craniofacial dysmorphism (including microcephaly, hypertelorism, downslanting palpebral fissures, large, prominent nasal root with funnel nose, small, low-set ears, long philtrum, drooping facial skin). Additional manifestations may include seizures, intellectual disability, congenital hip dislocation, inguinal hernia, and cortical and cerebellar malformations. Pretibial pseudo-ecchymotic skin lesions have occasionally been associated.
Autosomal recessive cutis laxa type 2B (ORPHA:357064)
A rare, hereditary, developmental defect with connective tissue involvement characterized by cutis laxa of variable severity, in utero growth restriction, congenital hip dislocation and joint hyperlaxity, wrinkling of the skin, in particular the dorsum of hands and feet, and progeroid facial features. Hypotonia, developmental delay, and intellectual disability are common. In addition, cataracts, corneal clouding, wormian bones, lipodystrophy and osteopenia have been reported.
Autosomal recessive distal osteolysis syndrome (ORPHA:2776)
An early-onset distal osteolysis characterised by severe resorption of the hands and feet and absence of the distal and middle phalanges. It has been described in a son and daughter born to consanguineous parents. Other manifestations include distal muscular hypertrophy, flexion contractures, short stature, mild intellectual deficit and characteristic facies (maxillary hypoplasia, exophthalmos, and a broad nasal tip). It is transmitted as an autosomal recessive trait.
Autosomal recessive distal renal tubular acidosis (ORPHA:402041)
A rare autosomal recessive 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 recessive epidermolytic ichthyosis (ORPHA:512103)
A rare, inherited, non-syndromic ichthyosis characterized by congenital, generalized erythroderma with cutaneous blistering and erosions, resembling collodion presentation at birth, replaced by progressive hyperkeratosis later in life without palmoplantar involvement. The ultrastructural pathology consists of sparse keratin filaments and keratin clumps that show a nearly homogeneous, amorphous structure.
Autosomal recessive extra-oral halitosis (ORPHA:562538)
A rare inborn error of metabolism characterized by cabbage-like breath odor with high levels of methanethiol and dimethylsulfide in oral and nasal breath, due to methanethiol oxidase deficiency. Laboratory examination shows elevated levels of dimethylsulfide, dimethylsulfoxide, and dimethylsulfone in blood, cerebrospinal fluid (CSF), and urine.
Autosomal recessive faciodigitogenital syndrome (ORPHA:1974)
A very rare syndrome including short stature, facial dysmorphism, hand abnormalities and shawl scrotum.
Epidemiology
It has been observed in 16 subjects from five distantly related sibships of a large Kuwaiti Bedouin tribe.
Clinical description
Dysmorphic features include triangular or elongated face, hypertelorism, wide palpebral fissures, short, stubby nose with anteverted nostrils, long philtrum and ear anomalies. The hands are small, broad with mild interdigital webbing, 5th finger clinodactyly and lax joints. In one sibship, affected patients had coarse, dry, and hypopigmented hair. The affected patients had no intellectual deficit.
Genetic counseling
In this tribe, the condition is transmitted as an autosomal recessive trait.

                            Last update: 
                            October 2010
Autosomal recessive frontotemporal pachygyria (ORPHA:329329)
A cerebral malformation characterized by symmetric, bilateral pachygyria with normal head circumference and without polymicrogyria. Clinical manifestations include developmental delay, moderate intellectual disability, normal or slightly decreased muscle tone and deep-tendon reflexes, telecanthus or hypertelorism.
Autosomal recessive generalized epidermolysis bullosa simplex (ORPHA:89838)
A rare, inherited, epidermolysis bullosa simplex characterized by neonatal onset of generalized or, less frequently, localized acral blistering. Milia are rare but atrophic scarring and dystrophic nails usually occur, along with focal keratoderma (palms and soles). Severe generalized blistering may cause perinatal death or persist during the entire life. Extracutaneous involvement is common, including anemia, growth retardation, oral cavity abnormalities (blisters and erosions, and caries) and constipation.
Autosomal recessive hyperinsulinism due to Kir6.2 deficiency (ORPHA:79644)
A rare, congenital, isolated hyperinsulinism disorder characterized by neonatal presentation of severe refractory hypoglycemia in the first two days of life, with limited response to medical management, sometimes requiring pancreatic resection. Newborns are often large for gestational age with mild to moderate hepatomegaly and diffuse form of hyperinsulinism due to Kir6.2 deficiency. Persistent hypoglycemia, hyperglycemia and type1 diabetes mellitus may develop later in life. Life-threatening hypoglycemic coma or status epilepticus have also been associated.
Autosomal recessive hyperinsulinism due to SUR1 deficiency (ORPHA:79643)
A rare, congenital, isolated hyperinsulinism disorder characterized by neonatal presentation of severe refractory hypoglycemia in the first two days of life, with limited response to medical management, sometimes requiring pancreatic resection. Newborns are often large for gestational age with mild to moderate hepatomegaly and diffuse form of hyperinsulinism due to SUR1 deficiency. Persistent hypoglycemia, hyperglycemia and type1 diabetes mellitus may develop later in life. Life-threatening hypoglycemic coma or status epilepticus have also been associated.
Autosomal recessive hypophosphatemic rickets (ORPHA:289176)
A rare, autosomal recessive renal phosphate-wasting disorder characterized by childhood-onset hypophosphatemia that clinically manifests with rickets and/or osteomalacia, slow growth/short stature, bone pain and skeletal deformities. Additional findings may include fatigue, muscle weakness and repeated bone fractures.
Autosomal recessive infantile hypercalcemia (ORPHA:300547)
A rare, genetic, phosphocalcic metabolism disorder characterized by early-onset hypercalcemia, hypophosphatemia, hypercalciuria, decreased intact parathyroid hormone serum levels and medullary nephrocalcinosis, typically manifesting with failure to thrive, hypotonia, vomiting, constipation and/or polyuria.
Autosomal recessive intermediate Charcot-Marie-Tooth disease type A (ORPHA:217055)
A subtype of autosomal recessive intermediate Charcot-Marie-Tooth (CMT) disease characterized by severe, early childhood-onset CMT neuropathy with prominent pes equinovarus deformity and impairment of hand muscles. Nerve conduction velocities usually range between 25-35 m/s and both axonal and demyelinating changes are observed on peripheral nerve pathology.
Autosomal recessive intermediate Charcot-Marie-Tooth disease type B (ORPHA:254334)
A rare subtype of autosomal recessive intermediate Charcot-Marie-Tooth (CMT) disease characterized by a CMT neuropathy associated with developmental delay, self-abusive behavior, dysmorphic features and vestibular Schwannoma. Motor nerve conduction velocities demonstrate features of both demyelinating and axonal pathology.
Autosomal recessive intermediate Charcot-Marie-Tooth disease type C (ORPHA:369867)
A rare subtype of autosomal recessive intermediate Charcot-Marie-Tooth (CMT) disease characterized by childhood to adulthood-onset of progressive, moderate to severe, predominantly distal, mostly lower limb muscle weakness and atrophy, foot deformities (including pes cavus and hammer toes), absent deep tendon reflexes and distal sensory loss associated with decreased motor and sensory nerve conduction velocities and features of both demyelinating and axonal neuropathy on sural nerve biopsy.