Objective: The authors describe and quantify the neuropsychiatric symptoms present in a cohort of males with the fragile X mental retardation 1 (FMR1) premutation allele who have developed fragile X–associated tremor/ataxia syndrome (FXTAS).

Method: Fourteen male carriers of the FMR1 premutation who had clinical manifestations of the FXTAS syndrome and 14 age-and educationmatched controls were assessed with the Neuropsychiatric Inventory (NPI), formal cognitive testing, and genetic analysis. Results: Males with FXTAS had significantly higher total NPI scores (p<. 004) and significantly higher scores on the agitation/aggression (p<. 004), depression (p<. 004), apathy (p<. 004), disinhibition (p<. 004), and irritability (p<. 004) scales, compared with controls. Cognitive performances on the Mini-Mental State Examination did not correlate with severity of symptoms on the NPI.

Conclusions: The neuropsychiatric manifestations of FXTAS, based on this preliminary report, appear to cluster as a fronto-subcortical dementia. Clinicians encountering patients with clinical dementia with motor symptoms suggesting FXTAS should consider genetic testing to determine whether the patient’s dementia syndrome is secondary to a fragile X premutation carrier status.