Fragile X-associated tremor/ataxia syndrome and movements disorders

Purpose of review Fragile X-associated tremor/ataxia syndrome (FXTAS) is a multiple-system neurologic disorder caused by expansion of 55-200 CGG repeats in the FMR1 (fragile site mental retardation 1) gene. The presence of both hyperkinetic and hypokinetic movement disorders such as ataxia, tremor, and parkinsonism are clinical features of FXTAS. The purpose of this review is to summarize the description of movement disorders associated with FXTAS and to discuss recent observations regarding the relationship between abnormal expansion in the FMR1 gene and development of neurodegenerative disorders. Recent findings The clinical expression of FXTAS occasionally resembles the phenotypes of other idiopathic neurodegenerative disorders. However, the unique pathological feature appearance of the intranuclear inclusions in the neurons and astrocytes, is discriminatory from those in other neurodegenerative disorders. Several studies found no association between the FMR1 gene premutation and development of other neurodegenerative disorders with similar movement disorders to FXTAS. However, a premutation expansion in the FMR1 gene may be a frequent genetic cause of late-onset sporadic ataxia with magnetic-resonance-image abnormality. Summary FXTAS exhibits various movement-disorder phenotypes. However, the FMR1 gene premutation is unlikely to be a common genetic cause of neurodegenerative disorders with tremor or ataxia. Patients with sporadic late-onset ataxia associated with magnetic-resonance-image abnormality should be considered for testing for a CGG-repeat expansion in the FMR1 gene.