Background: Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late onset, X-linked genetic, neurodegenerative disorder caused by a "premutation (PM)" in the fragile X mental retardation 1 (FMR1) gene. Here we report a case of FXTAS from mainland of China who presented with rare orthostatic tremor. A review of tremor of FXTAS in the literature is also included.
Case presentation: A 67-year-old right-handed farmer started with tremor of both legs 8 years ago which was present while standing but absent when sitting or lying and progressed with unsteady gait one and a half years ago. The brain MRI showed high intensity signal in the bilateral middle cerebellar peduncles (MCP) in T2-weighted and fluid-attenuated inversion recovery (FLAIR) images and gene test for premutation for FMR1 was positive with 101 CGG repeats. The patient met the the diagnosis of definite FXTAS. Clonazepam and topiramate were administered to control tremor. We reviewed the literature and identified 64 cases with detailed clinical and genetic information. Orthostatic tremor associated with FXTAS is very rare. We found 85.2% patients reported tremor,42.6% with intention tremor,36.1% with kinetic tremor,32.8% with rest tremor and 29.5% with posture tremor. 37.7% of patients who have tremor showed at least two types of tremor. There were 6 patients with isolated rest tremor. There was 2 patient with voice tremor and 6 with head tremor. We also found that 74.6% FXTAS patients had family history of FMR1 gene associated diseases including Fragile X syndrome (FXS), FXTAS or fragile X-associated primary ovarian insufficiency (FXPOI).
Conclusions: Adding our data to the available literature suggests that orthostatic tremor could be a rare initial manifestation of FXTAS and the review will increasing our understanding the phenotype of tremor in FXTAS. Family history of FMR1 gene associated diseases might be an important clue to the diagnosis.
Keywords: Ataxia; FMR1 gene,tremor; Fragile X-associated tremor/ Ataxia syndrome; Orthostatic tremor.