Journal Article

The fragile X tremor ataxia syndrome in the differential diagnosis of multiple system atrophy: data from the EMSA Study Group

C. Kamm, D. G. Healy, N. P. Quinn, U. Wüllner, J. C. Moller, L. Schols, F. Geser, K. Burk, A. D. Børglum, M. T. Pellecchia, E. Tolosa, F. del Sorbo, C. Nilsson, O. Bandmann, M. Sharma, P. Mayer, M. Gasteiger, A. Haworth, T. Ozawa, A. J. Lees, J. Short, P. Giunti, E. Holinski-Feder, T. Illig, H. E. Wichmann, G. K. Wenning, N. W. Wood and T. Gasser

in Brain

Published on behalf of The Guarantors of Brain

Volume 128, issue 8, pages 1855-1860
Published in print August 2005 | ISSN: 0006-8950
Published online June 2005 | e-ISSN: 1460-2156 | DOI:
The fragile X tremor ataxia syndrome in the differential diagnosis of multiple system atrophy: data from the EMSA Study Group

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The recent identification of fragile X-associated tremor ataxia syndrome (FXTAS) associated with premutations in the FMR1 gene and the possibility of clinical overlap with multiple system atrophy (MSA) has raised important questions, such as whether genetic testing for FXTAS should be performed routinely in MSA and whether positive cases might affect the specificity of current MSA diagnostic criteria. We genotyped 507 patients with clinically diagnosed or pathologically proven MSA for FMR1 repeat length. Among the 426 clinically diagnosed cases, we identified four patients carrying FMR1 premutations (0.94%). Within the subgroup of patients with probable MSA-C, three of 76 patients (3.95%) carried premutations. We identified no premutation carriers among 81 patients with pathologically proven MSA and only one carrier among 622 controls (0.16%). Our results suggest that, with proper application of current diagnostic criteria, FXTAS is very unlikely to be confused with MSA. However, slowly progressive disease or predominant tremor are useful red flags and should prompt the consideration of FXTAS. On the basis of our data, the EMSA Study Group does not recommend routine FMR1 genotyping in typical MSA patients.

Keywords: multiple system atrophy; FXTAS; fragile X; FMR1; premutation; EMSA-SG = European Multiple System Atrophy Study Group; FMR1 = fragile site mental retardation 1 gene; FXTAS = fragile X tremor ataxia syndrome; KORA = Cooperative Health Research in the Region of Augsburg; MSA = multiple system atrophy; MSA-C = multiple system atrophy with predominant cerebellar ataxia; REM = rapid eye movement

Journal Article.  4292 words. 

Subjects: Neurology ; Neuroscience

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