Clinical neurological phenotype of FXTAS

Maureen A. Leehey, Deborah A. Hall, Ying Liu, Randi J Hagerman

Research output: Chapter in Book/Report/Conference proceedingChapter

4 Scopus citations


The classic presentation of fragile X-associated tremor/ataxia syndrome (FXTAS) is an aging man with progressive cerebellar gait ataxia, kinetic tremor, mild parkinsonism, cognitive decline, especially executive dysfunction and short-term memory deficiency, and peripheral neuropathy. Autonomic dysfunction and mood/anxiety disorders 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 of the splenium of the corpus callosum, and pathology shows intranuclear inclusions, especially in brain. Recent studies, however, have shown that the FXTAS clinical picture is variable, for example, affected persons may have minor or no tremor and others have predominant dementia or peripheral neuropathy. Onset of motor signs in men is typically in the early 60s, and approximately 40 % of carrier men and 8-16 % of carrier women over age 50 develop the disorder. Penetrance is age related, such that 75 % of men ≤ 80 years of age are affected. While less data exist regarding FXTAS in carrier women, they appear to have similar but less severe motor signs, perhaps less cognitive impairment, and some different patterns of involvement than seen in men. FXTAS, at present, is underdiagnosed largely because the presentation is often a combination of signs which are common in the elderly and because affected persons often lack insight regarding their deficits and are resistant to seeking medical care. Furthermore, the heterogeneous nature of the disorder facilitates misdiagnosis, especially in the earlier stages. Diagnosis 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 or other premutation associated problems.

Original languageEnglish (US)
Title of host publicationFXTAS, FXPOI, and Other Premutation Disorders
PublisherSpringer International Publishing
Number of pages24
ISBN (Electronic)9783319338989
ISBN (Print)9783319338965
StatePublished - Jan 1 2016


  • Ataxia
  • Fragile X-associated tremor/ataxia syndrome
  • Intentional tremor
  • Neuropathy
  • Parkinsonism

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Neuroscience(all)


Dive into the research topics of 'Clinical neurological phenotype of FXTAS'. Together they form a unique fingerprint.

Cite this