Early symptoms in spinocerebellar ataxia type 1, 2, 3, and 6

Mov Disord. 2008 Nov 15;23(15):2232-8. doi: 10.1002/mds.22288.

Abstract

Onset of genetically determined neurodegenerative diseases is difficult to specify because of their insidious and slowly progressive nature. This is especially true for spinocerebellar ataxia (SCA) because of varying affection of many parts of the nervous system and huge variability of symptoms. We investigated early symptoms in 287 patients with SCA1, SCA2, SCA3, or SCA6 and calculated the influence of CAG repeat length on age of onset depending on (1) the definition of disease onset, (2) people defining onset, and (3) duration of symptoms. Gait difficulty was the initial symptom in two-thirds of patients. Double vision, dysarthria, impaired hand writing, and episodic vertigo preceded ataxia in 4% of patients, respectively. Frequency of other early symptoms did not differ from controls and was regarded unspecific. Data about disease onset varied between patients and relatives for 1 year or more in 44% of cases. Influence of repeat length on age of onset was maximum when onset was defined as beginning of permanent gait disturbance and cases with symptoms for more than 10 years were excluded. Under these conditions, CAG repeat length determined 64% of onset variability in SCA1, 67% in SCA2, 46% in SCA3, and 41% in SCA6 demonstrating substantial influence of nonrepeat factors on disease onset in all SCA subtypes. Identification of these factors is of interest as potential targets for disease modifying compounds. In this respect, recognition of early symptoms that develop before onset of ataxia is mandatory to determine the shift from presymptomatic to affected status in SCA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Ataxin-1
  • Ataxin-3
  • Ataxins
  • Calcium Channels / genetics
  • DNA Mutational Analysis
  • Female
  • Gait Disorders, Neurologic / complications
  • Humans
  • Linear Models
  • Male
  • Middle Aged
  • Nerve Tissue Proteins / genetics
  • Nuclear Proteins / genetics
  • Repressor Proteins / genetics
  • Spinocerebellar Ataxias* / classification
  • Spinocerebellar Ataxias* / complications
  • Spinocerebellar Ataxias* / genetics
  • Trinucleotide Repeat Expansion / genetics*
  • Young Adult

Substances

  • ATXN1 protein, human
  • Ataxin-1
  • Ataxins
  • CACNA1A protein, human
  • Calcium Channels
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Repressor Proteins
  • ATXN3 protein, human
  • Ataxin-3