Prevalence of fragile X-associated tremor/ataxia syndrome: A survey of essential tremor patients with cerebellar signs or extrapyramidal signs

Objectives: In screening studies of Western patients with cerebellar dysfunction, FMR1 premutations have been detected. A screening study of East Asian patients with presumed essential tremor (ET) did not detect these mutations, possibly because the ET patients did not closely mimic the phenotype of fragile X-associated tremor/ataxia syndrome (FXTAS). The aim of this study was to estimate the prevalence of FMR1 premutations in a carefully recruited group of ET patients with additional phenotypic features of FXTAS.

Materials and methods: From April 2014 to April 2018, we prospectively recruited patients with ET diagnoses from three tertiary care centers. Demographic and clinical data were collected, as well as data on presence of cerebellar signs and extrapyramidal signs (EPS). Tremor, cerebellar signs, and EPS were evaluated using appropriate clinical rating scales. For ET patients with additional cerebellar signs or EPS, FMR1 mutation analysis and brain magnetic resonance imaging were performed.

Results: Six hundred and three ET patients were recruited. Cerebellar signs or EPS were present in 168 (27.9%) of 603. FMR1 CGG repeat analysis was performed in 74 of 168 patients. Fifty-two of 74 had cerebellar signs only, three had EPS only, and 19 had both neurologic abnormalities. Two patients had a FMR1 premutation and fulfiled both clinical and radiological criteria of FXTAS.

Conclusions: Two (2.7%) of 74 patients with presumed ET and additional neurological features were discovered to have FXTAS. The possibility of FXTAS should be considered in patients with ET who exhibit mild cerebellar signs or EPS.