Autosomal dominant cerebellar ataxias: clinical features, genetics, and pathogenesis

Lancet Neurol. 2004 May;3(5):291-304. doi: 10.1016/S1474-4422(04)00737-9.


Autosomal dominant cerebellar ataxias are hereditary neurodegenerative disorders that are known as spinocerebellar ataxias (SCA) in genetic nomenclature. In the pregenomic era, ataxias were some of the most poorly understood neurological disorders; the unravelling of their molecular basis enabled precise diagnosis in vivo and explained many clinical phenomena such as anticipation and variable phenotypes even within one family. However, the discovery of many ataxia genes and loci in the past decade threatens to cause more confusion than optimism among clinicians. Therefore, the provision of guidance for genetic testing according to clinical findings and frequencies of SCA subtypes in different ethnic groups is a major challenge. The identification of ataxia genes raises hope that essential pathogenetic mechanisms causing SCA will become more and more apparent. Elucidation of the pathogenesis of SCA hopefully will enable the development of rational therapies for this group of disorders, which currently can only be treated symptomatically.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Death
  • Diagnostic Imaging / methods
  • Disease Models, Animal
  • Electrophysiology / methods
  • Genetic Linkage
  • Genotype
  • Humans
  • Incidence
  • Models, Neurological
  • Molecular Biology / methods
  • Neuropsychology / methods
  • Prevalence
  • Spinocerebellar Ataxias / classification
  • Spinocerebellar Ataxias / epidemiology*
  • Spinocerebellar Ataxias / genetics*
  • Spinocerebellar Ataxias / physiopathology
  • Trinucleotide Repeats / genetics*