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. 2003 Apr;72(4):869-78.
doi: 10.1086/374321. Epub 2003 Mar 12.

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

Sébastien Jacquemont  1 , 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
Affiliations

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

Sébastien Jacquemont et al. Am J Hum Genet. 2003 Apr.

Abstract

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.

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Figures

Figure 1
Figure 1
Executive function decline correlated to disease duration: linear and quadratic regression.
Figure 2
Figure 2
MRI findings, T2-weighted axial images of the cerebellum. a, Normal T2 weighted axial image of the cerebellum (arrows indicate cerebellar white matter). b and c, Symmetrical regions of increased T2 signal intensity in the MCPs. d–h, Adjacent cerebellar white matter.
Figure 3
Figure 3
Coronal inversion recovery image demonstrating severe parietal volume loss and increased signal intensity in the cerebellar white matter.
See this image and copyright information in PMC

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References

Electronic-Database Information

    1. Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim/ (for FMR1) - PubMed

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