Detection of early FXTAS motor symptoms using the CATSYS computerised neuromotor test battery

• Authors: Emily Graves Allen, Emory University; Jorge Juncos, Emory University; R Letz, Emory University; M Rusin, Emory University; Douglas H. Hamilton, Emory University; Gloria Novak, Emory University; L Shubeck, Emory University; S W Tinker, Emory University; Stephanie Sherman, Emory University
• Journal Title: Journal of Medical Genetics
• Volume: Volume 45, Number 5
• Publisher: BMJ Publishing Group | 2008-01-03, Pages 290-297
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1136/jmg.2007.054676
• Subjects: Health Sciences, General; Biology, Genetics

Abstract

Background Carriers of the FMR1 premutation allele are at a significantly increased risk for a late-onset neurodegenerative disorder, fragile X-associated tremor/ataxia syndrome (FXTAS). This disorder is distinct from fragile X syndrome (FXS) in its molecular aetiology and clinical presentation. The primary features of FXTAS are late-onset intention tremor and gait ataxia. Associated features include parkinsonism, neuropsychological dysfunction, autonomic dysfunction and peripheral neuropathy. Aim To investigate the usefulness of a quantitative neurological test battery implemented through the CATSYS instrument to identify preclinical symptoms of FXTAS. Methods Both premutation carriers with 70–199 repeats (62 men) and their low-repeat allele carrier siblings (27 men), identified through families with an individual affected with FXS, were tested. Results As expected, because of its sensitivity, use of the instrument allowed identification of tremor in 23% of men who had not self-reported tremor, and ataxia in 30% of men who had not self-reported ataxia. Among subjects with self-reported tremor and ataxia, we found significant concordance between measures of the CATSYS system and the self-report. Conclusion Rates of these traits among premutation carriers and low-repeat allele carrier siblings could be identified, and are presented in this paper, along with the minimum estimates of age-related prevalence.