Spinocerebellar ataxia type 6: gaze-evoked and vertical nystagmus, Purkinje cell degeneration, and variable age of onset

Ann Neurol. 1997 Dec;42(6):933-50. doi: 10.1002/ana.410420616.

Abstract

Spinocerebellar ataxia type 6 (SCA6) was recently identified as a form of autosomal dominant cerebellar ataxia associated with small expansions of the trinucleotide repeat (CAG)n in the gene CACNL1A4 on chromosome 19p13, which encodes the alpha1 subunit of a P/Q-type voltage-gated calcium channel. We describe clinical, genetic, neuroimaging, neuropathological, and quantitative oculomotor studies in four kindreds with SCA6. We found strong genetic linkage of the disease to the CACNL1A4 locus and strong association with the expanded (CAG)n alleles in two large ataxia kindreds. The expanded alleles were all of a single size (repeat number) within the two large kindreds, numbering 22 and 23 repeat units. It is noteworthy that the age of onset of ataxia ranged from 24 to 63 years among all affected individuals, despite the uniform repeat number. Radiographically and pathologically, there was selective atrophy of the cerebellum and extensive loss of Purkinje cells in the cerebellar cortex. In addition, clinical and quantitative measurement of extraocular movements demonstrated a characteristic pattern of ocular motor and vestibular abnormalities, including horizontal and vertical nystagmus and an abnormal vestibulo-ocular reflex. These studies identify a distinct phenotype associated with this newly recognized form of dominant SCA.

Publication types

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

MeSH terms

  • Adult
  • Age of Onset*
  • Aged
  • Aged, 80 and over
  • Alleles
  • Evoked Potentials, Visual*
  • Eye Movements
  • Female
  • Genetic Linkage
  • Humans
  • Lod Score
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Nerve Degeneration*
  • Nystagmus, Pathologic / pathology
  • Nystagmus, Pathologic / physiopathology*
  • Pedigree
  • Phenotype
  • Purkinje Cells*
  • Spinocerebellar Degenerations / complications
  • Spinocerebellar Degenerations / genetics
  • Spinocerebellar Degenerations / pathology*
  • Spinocerebellar Degenerations / physiopathology*