Autosomal dominant cerebellar ataxia

doi:10.1017/CBO9780511544873.048

47 - Autosomal dominant cerebellar ataxia

from Part VIII - Cerebellar degenerations

Published online by Cambridge University Press: 04 August 2010

Anthony E. Lang and

M. Flint Beal: Affiliation:
Cornell University, New York
Anthony E. Lang: Affiliation:
University of Toronto
Albert C. Ludolph: Affiliation:
Universität Ulm, Germany
Henry L. Paulson: Affiliation:
Department of Neurology, University of Iowa Hospitals and Clinics, IA, USA

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Summary

This review discusses clinical and genetic features of dominantly inherited ataxia. In addition, potential pathogenic mechanisms are discussed with a special focus on the polyglutamine disorders, since most is known about this group of diseases.

Classification of ADCA

Most adult onset hereditary ataxias are dominantly inherited. Harding (1993) clinically divided autosomal dominant cerebellar ataxia (ADCA) into four types, I through IV. Type I ADCA represents cerebellar disease accompanied by brainstem signs. ADCA type II is similar to type I but also includes retinopathy. ADCA type III represents later onset, “pure” cerebellar disease and ADCA type IV represents episodic ataxia.

A newer, favored classification for ADCA reflects the growing number of identified genetic loci, each of which is designated a specific spinocerebellar ataxia or SCA (Table 47.1). As SCAs are mapped to loci, they are assigned numbers – SCA1, SCA2 and so forth, currently up to 21 at the time of this writing. Most SCAs fall within Harding's ADCA type I classification. There is considerable clinical overlap among the ADCA type I group, even within families. In contrast, the sole genetic cause of ADCA type II appears to be SCA7, the only dominant ataxia routinely accompanied by retinal degeneration. Most patients with SCA6 (and several rarer SCAs for which the gene defects have not been identified) manifest as a pure cerebellar syndrome and thus fall within ADCA III. Finally, ADCA type IV currently consists of two genetically identified forms of episodic ataxia (EA), EA-1 and EA-2, caused by mutations in a potassium and calcium channel respectively.

Type: Chapter
Information: Neurodegenerative Diseases
Neurobiology, Pathogenesis and Therapeutics
, pp. 709 - 718

DOI: https://doi.org/10.1017/CBO9780511544873.048 [Opens in a new window]

Publisher: Cambridge University Press

Print publication year: 2005

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