Penetrance of the Fragile X–Associated Tremor/Ataxia Syndrome in a Premutation Carrier Population

To study the penetrance of the fragile X-associated tremor/ataxia syndrome (FXTAS) among premutation carriers. DESIGN, SETTING, AND PARTICIPANTS: Family-based study of 192 individuals (premutation carriers and controls) whose families belong to the Northern or Southern California Fragile X Associations. Data were collected (March 2002-April 2003) through a survey and a standardized neurological examination, which was videotaped and subsequently scored in a blinded fashion. MAIN OUTCOME MEASURES: Penetrance of intention tremor and ataxia among adult carriers (aged > or =50 years) of premutation expansions of the FMR1 gene.

Data from the survey of 192 individuals demonstrated an age-related penetrance of the combination of reported intention tremor and gait ataxia in male carriers (17%, 38%, 47%, and 75% [lower-bound estimates] for participants aged 50-59, 60-69, 70-79, and > or =80 years, respectively). The male carrier group had an age-adjusted 13-fold increased risk (95% confidence interval, 3.9-25.4; P =.003) of combined intention tremor and gait ataxia when compared with male controls. The clinical examination data from 93 individuals demonstrated that male carriers experienced more difficulties on each of 3 standardized neurological rating scales compared with controls (P