title: Gait and Functional Mobility Deficits in Fragile X-Associated Tremor/Ataxia Syndrome.
abstract: Fragile X-associated tremor/ataxia syndrome (FXTAS) results from a "premutation" (PM) size CGG repeat expansion in the fragile X mental retardation 1 (FMR1) gene. Cerebellar gait ataxia is the primary feature in some FXTAS patients causing progressive disability. However, no studies have quantitatively characterized gait and mobility deficits in FXTAS. We performed quantitative gait and mobility analysis in seven FMR1 PM carriers with FXTAS and ataxia, six PM carriers without FXTAS, and 18 age-matched controls. We studied four independent gait domains, trunk range of motion (ROM), and movement transitions using an instrumented Timed Up and Go (i-TUG). We correlated these outcome measures with FMR1 molecular variables and clinical severity scales. PM carriers with FXTAS were globally impaired in every gait performance domain except trunk ROM compared to controls. These included total i-TUG duration, stride velocity, gait cycle time, cadence, double-limb support and swing phase times, turn duration, step time before turn, and turn-to-sit duration, and increased gait variability on several measures. Carriers without FXTAS did not differ from controls on any parameters, but double-limb support time was close to significance. Balance and disability scales correlated with multiple gait and movement transition parameters, while the FXTAS Rating Scale did not. This is the first study to quantitatively examine gait and movement transitions in FXTAS patients. Gait characteristics were consistent with those from previous cohorts with cerebellar ataxia. Sensitive measures like the i-TUG may help determine efficacy of interventions, characterize disease progression, and provide early markers of disease in FXTAS.
authors: Department of Anatomy and Cell Biology, Rush University Medical Center, 600 South Paulina Street, Office 505B, Chicago, IL, 60612, USA. joan_a_okeefe@rush.edu.
authors: Joan A
authors: JA
authors: O'Keefe
authors: Department of Anatomy and Cell Biology, Rush University Medical Center, 600 South Paulina Street, Office 505B, Chicago, IL, 60612, USA.
authors: Erin E
authors: EE
authors: Robertson-Dick
authors: Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
authors: Deborah A
authors: DA
authors: Hall
authors: Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.|Department of Pediatrics, Rush University Medical Center, Chicago, IL, USA.|Department of Biochemistry, Rush University Medical Center, Chicago, IL, USA.
authors: Elizabeth
authors: E
authors: Berry-Kravis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001259:Ataxia / Q000235:genetics / Q000503:physiopathology*; D001696:Biomechanical Phenomena; D015331:Cohort Studies; D004185:Disability Evaluation; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics; D005600:Fragile X Syndrome / Q000235:genetics / Q000503:physiopathology*; D005684:Gait; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D011187:Posture; D012720:Severity of Illness Index; D014202:Tremor / Q000235:genetics / Q000503:physiopathology*
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human
keywords: Cerebellar gait ataxia; Fragile X mental retardation 1 (FMR1) premutation carrier; Fragile X-associated tremor/ataxia syndrome (FXTAS); Inertial sensors; Instrumented Timed Up and Go (i-TUG)