Expanded Clinical Phenotype of Women with the FMR1 Premutation

2007

Fragile X-associated tremor/ataxia syndrome (FXTAS) is generally considered to be uncommon in older female carriers 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 with and without core features of FXTAS (tremor; gait ataxia), and 69 age-matched controls. Compared with controls, carriers with definite or probable FXTAS had greater medical comorbidity, with increased prevalence of thyroid disease, hypertension, seizures, peripheral neuropathy, and fibromyalgia, in addition to the typical symptoms of FXTAS? tremor and ataxia. The non-FXTAS premutation group had more complaints of chronic muscle pain, persistent paraesthesias in extremities, and history of tremor than controls. The spectrum of clinical involvement in female carriers with FXTAS is quite broad, encompassing a number of medical comorbidities 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.

Peer-reviewed publications in scholarly journals Published/In Press

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