Men with FMR1 premutation alleles of less than 71 CGG repeats have low risk of being affected with fragile X-associated tremor/ataxia syndrome (FXTAS)

J Med Genet. 2022 Jul;59(7):706-709. doi: 10.1136/jmedgenet-2021-107758. Epub 2021 Jul 28.


Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset condition characterised by cerebellar ataxia and intention tremor, usually found in individuals with FMR1 premutation alleles (PM-CGG expansion of 55-199 repeats). Population studies estimate that between 1 in 250 and 1 in 1600 men have a PM, with up to 45% of these men suggested to develop FXTAS by age 80. We used a Bayesian approach to compare the probability of finding a specific PM genotype in an ataxia population to a population control group and found an estimated penetrance of <1% (0.031%; CI 0.007% to 0.141%) for men with ≤70 CGGs. These findings suggest that men with a PM of ≤70 CGGs, who comprise the vast majority of those with a PM, have a much lower risk of being affected with FXTAS than previously suggested. This is an issue of growing importance for accurate genetic counselling, as those with a PM of ≤70 CGGs are increasingly detected through community carrier screening or neurodevelopmental assessment programmes.

Keywords: DNA repeat expansion; genetic counseling; human genetics; neurodegenerative diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged, 80 and over
  • Alleles
  • Ataxia / genetics
  • Bayes Theorem
  • Cerebellar Ataxia* / genetics
  • Fragile X Mental Retardation Protein* / genetics
  • Fragile X Syndrome* / epidemiology
  • Fragile X Syndrome* / genetics
  • Humans
  • Male
  • Tremor / genetics
  • Trinucleotide Repeat Expansion / genetics


  • FMR1 protein, human
  • Fragile X Mental Retardation Protein

Supplementary concepts

  • Fragile X Tremor Ataxia Syndrome