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Genetics of Recessive Ataxias

  • Chapter
Movement Disorder Genetics

Abstract

Autosomal recessive cerebellar ataxias (ARCA) comprise a heterogeneous group of rare and most often complex hereditary neurodegenerative diseases. In the last few years, an acceleration of new ARCA gene discovery, including microarrays and next-generation sequencing, has occurred. These techniques have also led to the description of mutations in known genes associated with unusual phenotypes and the demonstration that there is a continuum between ARCA and other neurodegenerative disorders. An ARCA should be considered in patients (1) with an age at onset before 30 years, (2) with other affected siblings, and (3) if consanguinity in the family is known. According to pathophysiological principles, the ARCA might be associated with further neurological, especially neuropathy, and extra-neurological symptoms. Thus, results of electromyography are of interest for the classification of ARCA as well as for the etiological investigation. Similarly, another key point is whether there is clear cerebellar atrophy on brain MRI or not. However, both electromyography and MRI may be normal at the onset of the disease and should be repeated later in such cases. Several common pathophysiological pathways for ARCA have been described so far, including mitochondrial dysfunction, DNA repair deficiency, abnormal protein folding, and degradation, paroxysmal disorders. The following chapter classifies ARCA according to an absence or involvement of the peripheral nervous system in: (1) ARCA with pure sensory neuropathy, (2) ARCA with motor and sensory polyneuropathy, and (3) ARCA without polyneuropathy.

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Authors and Affiliations

  1. Department of Neurology, University Hospital Würzburg, Würzburg, 97082, Germany

    Stephan Klebe MD

  2. Movement Disorders Unit, Department of Neurology, University Hospital of Strasbourg, Strasbourg, 67098, France

    Mathieu Anheim MD, PhD

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  1. Stephan Klebe MD
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  2. Mathieu Anheim MD, PhD
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Correspondence to Stephan Klebe MD .

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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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Klebe, S., Anheim, M. (2015). Genetics of Recessive Ataxias. In: Schneider, S., Brás, J. (eds) Movement Disorder Genetics. Springer, Cham. https://doi.org/10.1007/978-3-319-17223-1_12

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