Fragile X premutation tremor/ataxia syndrome: Molecular, clinical, and neuroimaging correlates

Sébastien Jacquemont, Randi J Hagerman, Maureen Leehey, Jim Grigsby, Lin Zhang, James A Brunberg, Claudia Greco, Vincent Des Portes, Tristan Jardini, Richard Levine, Elizabeth Berry-Kravis, W. Ted Brown, Stephane Schaeffer, John Kissel, Flora Tassone, Paul J Hagerman

Research output: Contribution to journalArticlepeer-review

576 Scopus citations


We present a series of 26 patients, all >50 years of age, who are carriers of the fragile X premutation and are affected by a multisystem, progressive neurological disorder. The two main clinical features of this new syndrome are cerebellar ataxia and/or intention tremor, which were chosen as clinical inclusion criteria for this series. Other documented symptoms were short-term memory loss, executive function deficits, cognitive decline, parkinsonism, peripheral neuropathy, lower limb proximal muscle weakness, and autonomic dysfunction. Symmetrical regions of increased T2 signal intensity in the middle cerebellar peduncles and adjacent cerebellar white matter are thought to be highly sensitive for this neurologic condition, and their presence is the radiological inclusion criterion for this series. Molecular findings include elevated mRNA and low-normal or mildly decreased levels of fragile X mental retardation 1 protein. The clinical presentation of these patients, coupled with a specific lesion visible on magnetic resonance imaging and with neuropathological findings, affords a more complete delineation of this fragile X premutation-associated tremor/ataxia syndrome and distinguishes it from other movement disorders.

Original languageEnglish (US)
Pages (from-to)869-878
Number of pages10
JournalAmerican Journal of Human Genetics
Issue number4
StatePublished - Apr 1 2003

ASJC Scopus subject areas

  • Genetics


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