Autosomal dominant cerebellar ataxia type I

A review of the phenotypic and genotypic characteristics

Nathaniel Robb Whaley, Shinsuke Fujioka, Zbigniew K Wszolek

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Type I autosomal dominant cerebellar ataxia (ADCA) is a type of spinocerebellar ataxia (SCA) characterized by ataxia with other neurological signs, including oculomotor disturbances, cognitive deficits, pyramidal and extrapyramidal dysfunction, bulbar, spinal and peripheral nervous system involvement. The global prevalence of this disease is not known. The most common type I ADCA 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 including spinal cord and peripheral nerve disease, cognitive impairment, cerebellar or supranuclear ophthalmologic signs, psychiatric problems, 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, 21 subtypes have been identified: SCA1-SCA4, SCA8, SCA10, SCA12-SCA14, SCA15/16, SCA17-SCA23, SCA25, SCA27, SCA28 and dentatorubral pallidoluysian atrophy (DRPLA). Type I ADCA can be further divided based on the proposed pathogenetic mechanism into 3 subclasses: subclass 1 includes type I ADCA caused by CAG repeat expansions such as 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. Subclass 3 contains disorders caused by specific gene deletions, missense mutation, and nonsense mutation and includes SCA13, SCA14, SCA15/16, SCA27 and SCA28. 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. Given the autosomal dominant pattern of inheritance, genetic counseling is essential and best performed in specialized genetic clinics. 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 ADCA and even among kindreds.

Original languageEnglish (US)
Article number33
JournalOrphanet Journal of Rare Diseases
Volume6
Issue number1
DOIs
StatePublished - 2011

Fingerprint

Cerebellar Ataxia
Spinocerebellar Ataxias
Ataxia
Progressive Myoclonic Epilepsy
Dysarthria
Gait Ataxia
Trinucleotide Repeat Expansion
Founder Effect
Speech Therapy
Spinal Nerves
Inheritance Patterns
Nonsense Codon
Sequence Deletion
Occupational Therapy
Poisons
Genetic Counseling
Gene Deletion
Peripheral Nervous System
Genetic Testing
Peripheral Nervous System Diseases

ASJC Scopus subject areas

  • Medicine(all)
  • Genetics(clinical)
  • Pharmacology (medical)

Cite this

Autosomal dominant cerebellar ataxia type I : A review of the phenotypic and genotypic characteristics. / Whaley, Nathaniel Robb; Fujioka, Shinsuke; Wszolek, Zbigniew K.

In: Orphanet Journal of Rare Diseases, Vol. 6, No. 1, 33, 2011.

Research output: Contribution to journalArticle

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