Article Text

Fragile X-Associated Tremor/Ataxia Syndrome
  1. Maureen A. Leehey, MD
  1. From the Department of Neurology, University of Colorado Denver, Aurora, CO.
  1. Received April 18, 2009.
  2. Accepted for publication May 18, 2009.
  3. Reprints: Maureen A. Leehey, MD, Department of Neurology, University of Colorado Denver, Box B185, AO1 Bldg, 12631 E 17th Ave, Aurora, CO 80045. E-mail: Maureen.leehey{at}
  4. This work was supported by the National Institutes of Health Interdisciplinary Research Consortium (Roadmap) grants UL1DE19583 and RL1AG032115 for P.J. Hagerman and R.J. Hagerman, respectively, the NINDS grant NS044299 for J. Grigsby, and the symposium was supported in part by a grant from the National Center for Research Resources (R13 RR023236).

Clinical Phenotype, Diagnosis, and Treatment


Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder caused by a CGG repeat expansion in the premutation range (55-200) in the fragile X mental retardation 1 gene. Onset is typically in the early seventh decade, and men are principally affected. The major signs are cerebellar gait ataxia, intention tremor, frontal executive dysfunction, and global brain atrophy. Other frequent findings are parkinsonism (mild), peripheral neuropathy, psychiatric symptoms (depression, anxiety, and agitation), and autonomic dysfunction. The clinical presentation is heterogeneous, with individuals presenting with varied dominating signs, such as tremor, dementia, or neuropathy. Magnetic resonance imaging shows atrophy and patchy white matter lesions in the cerebral hemispheres and middle cerebellar peduncles. The latter has been designated the middle cerebellar peduncle sign, which occurs in about 60% of affected men, and is relatively specific for FXTAS. Affected females generally have less severe disease, less cognitive decline, and some symptoms different from that of men, for example, muscle pain. Management of FXTAS is complex and includes assessment of the patient's neurological and medical deficits, treatment of symptoms, and provision of relevant referrals, especially genetic counseling. Treatment is empirical, based on anecdotal experience and on knowledge of what works for symptoms of other disorders that also exist in FXTAS. Presently, the disorder is underrecognized because the first published report was only in 2001 and because the presentation is variable and mainly consists of a combination of signs common in the elderly. However, accurate diagnosis is critical for the patient and for the family because they need education regarding their genetic and health risks.

Key Words
  • fragile X-associated tremor/ataxia syndrome
  • fragile X mental retardation 1 gene
  • treatment

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