Functional motor control deficits in older FMR1 premutation carriers

Individuals with fragile X mental retardation 1 (FMR1) gene premutations are at increased risk for fragile X-associated tremor/ataxia syndrome (FXTAS) during aging. However, it is unknown whether older FMR1 premutation carriers, with or without FXTAS, exhibit functional motor control deficits compared with healthy individuals. The purpose of this study, therefore, was to determine whether older FMR1 premutation carriers exhibit impaired ability to perform functional motor tasks. Eight FMR1 premutation carriers (age: 58.88 ± 8.36 years) and eight age- and sex-matched healthy individuals (60.13 ± 9.25 years) performed (1) a steady isometric force control task with the index finger at 20% of their maximum voluntary contraction (MVC) and; (2) a single-step task. During the finger abduction task, firing rate of multiple motor units of the first dorsal interosseous (FDI) muscle was recorded. Compared with healthy controls, FMR1 premutation carriers exhibited (1) greater force variability (coefficient of variation of force) during isometric force (1.48 ± 1.02 vs. 0.63 ± 0.37%; P = 0.04); (2) reduced firing rate of multiple motor units during steady force, and; (3) reduced velocity of their weight transfer during stepping (156.62 ± 26.24 vs. 191.86 ± 18.83 cm/s; P = 0.01). These findings suggest that older FMR1 premutation carriers exhibit functional motor control deficits that reflect either subclinical issues associated with premutations independent of FXTAS, or prodromal markers of the development of FXTAS.