The classic presentation of fragile X-associated tremor/ataxia syndrome (FXTAS) is an aging man with progressive cerebellar gait ataxia, kinetic tremor, mild parkinsonism, and cognitive decline, especially executive dysfunction. Peripheral neuropathy and autonomic dysfunction may be present. MR imaging often reveals global brain atrophy and white matter changes, including hyperintensities of the middle cerebellar peduncles, termed the MCP sign, and pathology shows intranuclear inclusions in brain. Recent studies, however, have shown that the FXTAS clinical picture is heterogeneous, with variations, for example, that include persons with minor or no tremor and others with predominant dementia or peripheral neuropathy. Onset of motor signs in males is typically in the early 60s, and approximately 40% of male carriers over age 50 and 8% of female carriers over age 40 develop the disorder. Penetrance is age related, such that 75% of men ≥80 years of age are affected. While much less data exist regarding FXTAS in female carriers, they appear to have similar but less severe motor signs, perhaps less cognitive impairment, and some different patterns of involvement than seen in males. FXTAS, at present, is underdiagnosed largely because the presentation is often a combination of signs which are common in the elderly. Furthermore, the heterogeneous nature of the disorder facilitates misdiagnosis, especially in the earlier stages. Diagnostic evaluation requires FMR1 gene testing. Accurate diagnosis is not only important for the affected person but also for their family, as immediate family members may be at risk of having progeny with fragile X syndrome.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)