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

Kamm, C; Healy, DG; Quinn, NP; Wullner, U; Moller, JC; Schols, L; Geser, F; Burk, K; Borglum, AD and Pellecchia, MT, et al. (2005) In Brain 128(8). p.1855-1860
Abstract
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... (More)
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. (Less)
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published
subject
keywords
fragile X, FXTAS, premutation, FMR1, multiple system atrophy
in
Brain
volume
128
issue
8
pages
1855 - 1860
publisher
Oxford University Press
external identifiers
  • pmid:15947063
  • wos:000230724500013
  • scopus:23444442557
ISSN
1460-2156
DOI
10.1093/brain/awh535
language
English
LU publication?
yes
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dc3554eb-3b1a-4646-bc1e-670f9ed1d314 (old id 232158)
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2007-09-28 11:26:25
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2017-07-30 03:31:57
@article{dc3554eb-3b1a-4646-bc1e-670f9ed1d314,
  abstract     = {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.},
  author       = {Kamm, C and Healy, DG and Quinn, NP and Wullner, U and Moller, JC and Schols, L and Geser, F and Burk, K and Borglum, AD and Pellecchia, MT and Tolosa, E and del Sorbo, F and Nilsson, Christer and Bandmann, O and Sharma, M and Mayer, P and Gasteiger, M and Haworth, A and Ozawa, T and Lees, AJ and Short, J and Giunti, P and Holinski-Feder, E and Illig, T and Wichmann, HE and Wenning, GK and Wood, NW and Gasser, T},
  issn         = {1460-2156},
  keyword      = {fragile X,FXTAS,premutation,FMR1,multiple system atrophy},
  language     = {eng},
  number       = {8},
  pages        = {1855--1860},
  publisher    = {Oxford University Press},
  series       = {Brain},
  title        = {The fragile X tremor ataxia syndrome in the differential diagnosis of multiple system atrophy: data from the EMSA Study Group},
  url          = {http://dx.doi.org/10.1093/brain/awh535},
  volume       = {128},
  year         = {2005},
}