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Autosomal dominant cerebellar ataxia type I
A group of spinocerebellar ataxias (SCAs) characterized by ataxia with other neurological signs, including oculomotor disturbances, cognitive deficits, pyramidal and extrapyramidal dysfunction, bulbar, spinal and peripheral nervous system involvement.
ORPHA:94145Classification level: Group of disorders
- Autosomal dominant cerebellar ataxia type 1
- Cerebellar plus syndrome
- Prevalence: Unknown
- Inheritance: Autosomal dominant
- Age of onset: All ages
- ICD-10: G11.8
- OMIM: -
- UMLS: -
- MeSH: -
- GARD: -
- MedDRA: -
The overall prevalence of SCAs is 1/33,000-1/50,000. The prevalence of ADCA (all types) is estimated at 1/37,000 worldwide. The most common ADCA type I is SCA3 followed by SCA2, SCA1, and SCA8, in descending order. Founder effects no doubt contribute to the variable prevalence between populations.
Onset is usually in adulthood but cases of presentation in childhood have been reported. Clinical features vary depending on the SCA subtype but by definition include ataxia associated with other neurological manifestations. The clinical spectrum ranges from pure cerebellar signs to constellations that include spinal cord and peripheral nerve disease, cognitive impairment, cerebellar or supranuclear ophthalmologic signs, psychiatric disorders, and seizures. Cerebellar ataxia can affect virtually any body part causing movement abnormalities. Gait, truncal, and limb ataxia are often the most obvious cerebellar findings though nystagmus, saccadic abnormalities, and dysarthria are usually associated.
To date, 27 subtypes have been identified: SCA1-SCA4, SCA8, SCA10, SCA12- SCA14, SCA15/SCA16, SCA17- SCA23, SCA25, SCA27, SCA28, SCA32, SCA34- SCA37, autosomal dominant cerebellar ataxia, deafness and narcolepsy, and dentatorubral pallidoluysian atrophy (DRPLA) (see these terms). ADCA type I can be further divided based on the proposed pathogenetic mechanism into 3 subclasses. Subclass 1 includes ADCA type I caused by CAG repeat expansions such as in SCA1-SCA3, SCA17 and DRPLA. Subclass 2 includes trinucleotide repeat expansions that fall outside of the protein-coding regions of the disease gene including SCA8, SCA10 and SCA12, as well as hexanucleotide repeat expansions that fall outside of the protein-coding regions of the disease gene including SCA36. Subclass 3 contains disorders caused by specific gene deletions, missense mutation, and nonsense mutation and includes SCA13, SCA14, SCA15/SCA16, SCA27- SCA28 and SCA35.
Diagnosis is based on clinical history, physical examination, genetic molecular testing, and exclusion of other diseases.
Differential diagnosis is broad and includes secondary ataxias caused by drug or toxic effects, nutritional deficiencies, endocrinopathies, infections and post-infection states, structural abnormalities, paraneoplastic conditions and certain neurodegenerative disorders.
Prenatal diagnosis is possible in families with a known disease causing mutation.
Given the autosomal dominant pattern of inheritance, genetic counseling is essential and best performed in specialized genetic clinics.
Management and treatment
There are currently no known effective treatments to modify disease progression. Care is therefore supportive. Occupational and physical therapy for gait dysfunction and speech therapy for dysarthria is essential.
Prognosis is variable depending on the type of SCA and even among kindreds.
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