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Autosomal Dominant Cerebellar Ataxia Type I: A Review of the Phenotypic and Genotypic Characteristics

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Review

Autosomal Dominant Cerebellar Ataxia Type I: A Review of the Phenotypic and Genotypic Characteristics

Nathaniel Robb Whaley et al. Orphanet J Rare Dis.

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.

Figures

Figure 1
Figure 1
The MR (T1) brain (A) sagittal, (B) axial in a 54 year old African-American male with clinically genetically confirmed SCA2 who presented with cerebellar ataxia, dysarthria, slowed saccades, and peripheral neuropathy demonstrates cerebellar and brainstem atrophy.

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References

    1. Harding AE. The clinical features and classification of the late onset autosomal dominant cerebellar ataxias. A study of 11 families, including descendants of the 'the Drew family of Walworth'. Brain. 1982;105(Pt 1):1–28. - PubMed
    1. Whaley N, Uitti R. In: Neurology and Clinical Neuroscience. Schapira A, editor. Philadelphia: Mosby Inc; 2007. Inherited ataxias; pp. 887–897.
    1. Duenas AM, Goold R, Giunti P. Molecular pathogenesis of spinocerebellar ataxias. Brain. 2006;129(Pt 6):1357–1370. - PubMed
    1. van de Warrenburg BP, Sinke RJ, Verschuuren-Bemelmans CC, Scheffer H, Brunt ER, Ippel PF, Maat-Kievit JA, Dooijes D, Notermans NC, Lindhout D, Knoers NV, Kremer HP. Spinocerebellar ataxias in the Netherlands: prevalence and age at onset variance analysis. Neurology. 2002;58(5):702–708. - PubMed
    1. Craig K, Keers SM, Archibald K, Curtis A, Chinnery PF. Molecular epidemiology of spinocerebellar ataxia type 6. Annals of Neurology. 2004;55(5):752–755. doi: 10.1002/ana.20110. - DOI - PubMed

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