July 27, 2015: Fragile X associated tremor/ataxia syndrome

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July 27, 2015

Fragile X associated tremor/ataxia syndrome

Fragile X associated tremor/ataxia syndrome is a neurodegenerative disorder, manifesting after the age of 501. The phenotype is variable though individuals often present with an intention tremor followed by ataxia. As the disorder progresses, there can be emergence of parkinsonism, memory loss and executive dysfunction. Less commonly, there can be autonomic dysfunction or peripheral neuropathy2. The Fragile X associated tremor/ataxia syndrome is caused by mutations in the FMR1 gene, which encodes a regulatory protein involved in synaptic development. The causative mutations results in a CGG triplet repeat expansion. While normal individuals carry 5 to 40 repeats, individuals with Fragile X associated tremor/ataxia syndrome carry 55 to 200 repeats, and those with Fragile X syndrome carry more than 200 repeats. Penetrance is incomplete, with 40% of males and 16% of females with the expansion developing disease.


  1. Jacquemont S, Hagerman RJ, Leehey MA, et al. Penetrance of the fragile X-associated tremor/ataxia syndrome in a permutation carrier population. JAMA 2004; 291: 460-469.
  2. Leehey MA. Fragile X-associated tremor/ataxia syndrome: clinical phenotype, diagnosis, and treatment. Journal of Investigative Medicine 2009; 57: 830-836.

Submitted by Adam Numis MD, University of California, Los Angeles.

Disclosures: Dr. Numis is a member of the Residents & Fellows Section of Neurology.

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