Clinical and genetic analysis of a four-generation family with a distinct autosomal dominant cerebellar ataxia

J Neurol. 2001 Feb;248(2):113-20. doi: 10.1007/s004150170245.

Abstract

The autosomal dominant cerebellar ataxias (ADCAs) are a heterogeneous group of neurodegenerative disorders characterised by progressive cerebellar dysfunction in combination with a variety of other associative features. Since 1993 ADCAs have been increasingly characterised in terms of their genetic mutation and are referred to as spinocerebellar ataxias (SCAs). Some families with ADCA cannot be assigned to any of the known genotypes, which implies further genetic heterogeneity. We investigated the clinical symptoms of 12 patients of a four-generation family with ADCA and carried out mutation and genetic linkage studies. The family showed a relatively mild cerebellar ataxic syndrome with cognitive impairment, poor performance on the Wisconsin Card Sorting Test, myoclonus, and a postural irregular tremor of slow frequency. Age at disease onset and severity of cerebellar signs and symptoms suggest anticipation. The genetic loci implicated in ADCA were excluded by mutation analyses (SCA 1, 2, 3, 6, 7, 8, 12) and genetic linkage (SCA 4, 5, 6, 10, 11). We conclude that this family represents a clinically and genetically distinct form of SCA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Brain / pathology
  • Brain / physiopathology
  • Cerebellar Ataxia / genetics*
  • Cerebellar Ataxia / physiopathology
  • Cerebellar Ataxia / psychology
  • Child
  • Electrophysiology
  • Family Characteristics
  • Genetic Linkage / genetics*
  • Humans
  • Middle Aged
  • Neuropsychological Tests
  • Pedigree
  • Spinocerebellar Ataxias / genetics*
  • Spinocerebellar Ataxias / physiopathology
  • Spinocerebellar Ataxias / psychology