Progression of tremor and ataxia in male carriers of the FMR1 premutation

Mov Disord. 2007 Jan 15;22(2):203-6. doi: 10.1002/mds.21252.

Abstract

Premutation alleles of the fragile X mental retardation 1 (FMR1) gene give rise to a late-onset movement disorder, fragile X-associated tremor/ataxia syndrome (FXTAS), characterized by progressive intention tremor and gait ataxia, with associated dementia and global brain atrophy. The natural history of FXTAS is largely unknown. To address this issue, a family-based, retrospective, longitudinal study was conducted with a cohort of 55 male premutation carriers. Analysis of the progression of the major motor signs of FXTAS, tremor and ataxia, shows that tremor usually occurs first, with median onset at approximately 60 years of age. From the onset of the initial motor sign, median delay of onset of ataxia was 2 years; onset of falls, 6 years; dependence on a walking aid, 15 years; and death, 21 years. Preliminary data on life expectancy are variable, with a range from 5 to 25 years.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • Aged, 80 and over
  • Ataxia / epidemiology
  • Ataxia / genetics*
  • Ataxia / physiopathology*
  • Chromosomes, Human, X / genetics
  • Disease Progression
  • Follow-Up Studies
  • Fragile X Mental Retardation Protein / genetics
  • Fragile X Mental Retardation Protein / physiology*
  • Gene Silencing / physiology
  • Heterozygote*
  • Humans
  • Male
  • Middle Aged
  • Point Mutation / genetics*
  • Retrospective Studies
  • Severity of Illness Index
  • Time Factors
  • Tremor / epidemiology
  • Tremor / genetics*
  • Tremor / physiopathology*

Substances

  • FMR1 protein, human
  • Fragile X Mental Retardation Protein