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Genetics of Dominant Ataxias

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Movement Disorder Genetics

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Abstract

Dominant ataxias represent a clinically and genetically heterogeneous group of hereditary disorders comprising autosomal dominant spinocerebellar ataxias (ADCAs, SCAs) and episodic ataxias (EAs). From the clinical point of view, patients with ADCA exhibit a progressive cerebellar syndrome, either isolated or in combination with extra-cerebellar deficits. EAs are characterized by recurrent episodes of dizziness and ataxia, occurring either in a context of interictal neurological deficits or not. Current genetic classification includes 32 SCA loci (numbered from SCA1 to SCA36, plus dentatorubropallidoluysian atrophy DRPLA) and 7 EA loci (numbered from EA1 to EA7). A group of 12 ADCAs are related to an expansion of CAG repeats (polyglutaminopathies) or to repeats outside the coding region. Disease progression and severity are correlated with the repeat size. Anticipation is due to an instability of the expanded allele during transmission. The other ADCAs are due to conventional gene mutations. Overall, the causative gene is identified in about 60 % of dominant ataxias. There is still no cure for this group of disabling degenerative diseases. Current management is symptomatic.

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Authors and Affiliations

  1. Neurologie, FNRS, ULB-Erasme, Bruxelles, 1070, Belgium

    Mario Manto MD, PhD

  2. Parkinson Disease Area, UCB Pharma S.A., Braine-l’Alleud, 1420, Belgium

    Daniele Marmolino PhD

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  1. Mario Manto MD, PhD
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Correspondence to Mario Manto MD, PhD .

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Editors and Affiliations

  1. Department of Neurology, University Hospital Kiel, Kiel, Germany

    Susanne A. Schneider

  2. Department of Molecular Neuroscience, University College London, Institute of Neurology, London, United Kingdom

    José M. Tomás Brás

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Manto, M., Marmolino, D. (2015). Genetics of Dominant Ataxias. In: Schneider, S., Brás, J. (eds) Movement Disorder Genetics. Springer, Cham. https://doi.org/10.1007/978-3-319-17223-1_11

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