Expanded clinical phenotype of women with the FMR1 premutation

Sarah M. Coffey, Kylee Cook, Nicole Tartaglia, Flora Tassone, Danh V. Nguyen, Ruiqin Pan, Hannah E. Bronsky, Jennifer Yuhas, Mariya Borodyanskaya, Jim Grigsby, Melanie Doerflinger, Paul J Hagerman, Randi J Hagerman

Research output: Contribution to journalArticlepeer-review

259 Scopus citations


Fragile X-associated tremor/ataxia syndrome (FXTAS) is generally considered to be uncommon in older female carriers of premutation alleles (55-200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene; however, neither prevalence, nor the nature of the clinical phenotype, has been well characterized in female carriers. In this study, we evaluated 146 female carriers (mean, 42.3 years; range, 20-75 years) with and without core features of FXTAS (tremor; gait ataxia), and 69 age-matched controls (mean, 45.8 years; range, 21-78 years). Compared with controls, carriers with definite or probable FXTAS had greater medical co-morbidity, with increased prevalence of thyroid disease (P=0.0096), hypertension (P=0.0020), seizures (P=0.0077), peripheral neuropathy (P=0.0040), and fibromyalgia (P=0.0097), in addition to the typical symptoms of FXTAS-tremor (P<0.0001) and ataxia (P<0.0001). The non-FXTAS premutation group had more complaints of chronic muscle pain (P=0.0097), persistent paraesthesias in extremities (P< 0.0001), and history of tremor (P<0.0123) than controls. The spectrum of clinical involvement in female carriers with FXTAS is quite broad, encompassing a number of medical co-morbidities as well as the core movement disorder. The remarkable degree of thyroid dysfunction (17% in the non-FXTAS group and 50% in the FXTAS group) warrants consideration of thyroid function studies in all female premutation carriers, particularly those with core features of FXTAS.

Original languageEnglish (US)
Pages (from-to)1009-1016
Number of pages8
JournalAmerican Journal of Medical Genetics, Part A
Issue number8
StatePublished - Apr 15 2008


  • Fragile X premutation
  • Hypothyroidism
  • Neuropathy

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics
  • Medicine(all)


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