title: The fragile X tremor ataxia syndrome in the differential diagnosis of multiple system atrophy: data from the EMSA Study Group.
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.
authors.affiliation: Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, Hoppe-Seyler-Strasse 3, University of Tübingen, 72086 Tübingen, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Kamm
authors.forename: D G
authors.initials: DG
authors.lastname: Healy
authors.forename: N P
authors.initials: NP
authors.lastname: Quinn
authors.forename: U
authors.initials: U
authors.lastname: Wüllner
authors.forename: J C
authors.initials: JC
authors.lastname: Moller
authors.forename: L
authors.initials: L
authors.lastname: Schols
authors.forename: F
authors.initials: F
authors.lastname: Geser
authors.forename: K
authors.initials: K
authors.lastname: Burk
authors.forename: A D
authors.initials: AD
authors.lastname: Børglum
authors.forename: M T
authors.initials: MT
authors.lastname: Pellecchia
authors.forename: E
authors.initials: E
authors.lastname: Tolosa
authors.forename: F
authors.initials: F
authors.lastname: del Sorbo
authors.forename: C
authors.initials: C
authors.lastname: Nilsson
authors.forename: O
authors.initials: O
authors.lastname: Bandmann
authors.forename: M
authors.initials: M
authors.lastname: Sharma
authors.forename: P
authors.initials: P
authors.lastname: Mayer
authors.forename: M
authors.initials: M
authors.lastname: Gasteiger
authors.forename: A
authors.initials: A
authors.lastname: Haworth
authors.forename: T
authors.initials: T
authors.lastname: Ozawa
authors.forename: A J
authors.initials: AJ
authors.lastname: Lees
authors.forename: J
authors.initials: J
authors.lastname: Short
authors.forename: P
authors.initials: P
authors.lastname: Giunti
authors.forename: E
authors.initials: E
authors.lastname: Holinski-Feder
authors.forename: T
authors.initials: T
authors.lastname: Illig
authors.forename: H E
authors.initials: HE
authors.lastname: Wichmann
authors.forename: G K
authors.initials: GK
authors.lastname: Wenning
authors.forename: N W
authors.initials: NW
authors.lastname: Wood
authors.forename: T
authors.initials: T
authors.lastname: Gasser
mesh_terms: D000368:Aged; D001259:Ataxia / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D002524:Cerebellar Ataxia / Q000150:complications / Q000175:diagnosis / Q000235:genetics; D015331:Cohort Studies; D003937:Diagnosis, Differential; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D010523:Peripheral Nervous System Diseases / Q000150:complications / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D014202:Tremor / Q000150:complications / Q000175:diagnosis / Q000235:genetics*
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human