A low-symptomatic form of neurodegeneration in younger carriers of the FMR1 premutation, manifesting typical radiological changes

Danuta Z Loesch ^1*, Mark Cook ², Lucas Litewka ², Emma Gould ¹, Andrew Churchyard ³, Flora Tassone ⁴, Howard Robert Slater ⁵ and Elsdon Storey ⁶

¹ School of Psychological Science, La Trobe University, Victoria 3086, Australia, Australia
² Department of Clinical Neuroscience and Neurological Research, St Vincent’s Hospital, Australia
³ Southern Health Network, Victoria, Australia, Australia
⁴ University of Colorado School of Medicine, United States
⁵ Murdoch Childrens Research Institute, Australia
⁶ Van Cleef Roet Centre for Nervous Diseases, Monash University (Alfred Hospital Campus), Victoria,, Australia

^* To whom correspondence should be addressed. E-mail: d.loesch{at}latrobe.edu.au.

Accepted 14 November 2007

Abstract

Fragile X-associated tremor/ataxia (FXTAS) is a late-onset disorder caused by a premutation in the FMR1 gene, in which neurological symptoms are associated with white matter (wm) changes, especially within the middle cerebellar peduncles (MCP sign), seen on MRIs. We report a discrepancy between obvious radiological presentations and minimal clinical involvement in two younger male premutation carriers. These carriers, aged 52 and 39 years, showed distinct MCP sign, but reported no neurological symptoms. If this discrepancy represents the initial stage of FXTAS, our findings suggest the possibility of early diagnosis from MRI scans.

Keywords: FMR1 premutation, Fragile X, MRI, middle cerebellar peduncles MCP, tremor/ataxia

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