title: Characterization and Early Detection of Balance Deficits in Fragile X Premutation Carriers With and Without Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS).
abstract: Fragile X-associated tremor/ataxia syndrome (FXTAS) results from a "premutation" size 55-200 CGG repeat expansion in the fragile X mental retardation 1 (FMR1) gene. Core motor features include cerebellar gait ataxia and kinetic tremor, resulting in progressive mobility disability. There are no published studies characterizing balance deficits in FMR1 premutation carriers with and without FXTAS using a battery of quantitative measures to test the sensory integration underlying postural control, automatic postural reflexes, and dynamic postural stability limits. Computerized dynamic posturography (CDP) and two performance-based balance measures were administered in 44 premutation carriers, 21 with FXTAS and 23 without FXTAS, and 42 healthy controls to compare balance and functional mobility between these groups. Relationships between FMR1 molecular variables, age, and sex and CDP scores were explored. FXTAS subjects demonstrated significantly lower scores on the sensory organization test (with greatest reductions in the vestibular control of balance), longer response latencies to balance perturbations, and reduced stability limits compared to controls. Premutation carriers without FXTAS also demonstrated significantly delayed response latencies and disrupted sensory weighting for balance control. Advancing age, male sex, increased CGG repeat size, and reduced X activation of the normal allele in premutation carrier women predicted balance dysfunction. These postural control deficits in carriers with and without FXTAS implicate dysfunctional cerebellar neural networks and may provide valuable outcome markers for tailored rehabilitative interventions. Our findings suggest that CDP may provide sensitive measures for early detection of postural control impairments in at-risk carriers and better characterize balance dysfunction and progression in FXTAS.
authors.affiliation: Department of Anatomy and Cell Biology, Rush University Medical Center, Suite 507 Armour Academic Facility, 600 S. Paulina Street, Chicago, IL, 60612, USA. joan_a_okeefe@rush.edu.
authors.forename: Joan A
authors.initials: JA
authors.lastname: O'Keefe
authors.affiliation: Department of Anatomy and Cell Biology, Rush University Medical Center, Suite 507 Armour Academic Facility, 600 S. Paulina Street, Chicago, IL, 60612, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: Robertson-Dick
authors.affiliation: Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
authors.forename: Emily J
authors.initials: EJ
authors.lastname: Dunn
authors.affiliation: Department of Internal Medicine, Rush University Medical Center, Chicago, IL, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Internal Medicine, Rush University Medical Center, Chicago, IL, USA.
authors.forename: Youping
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Rush Medical College, Rush University Medical Center, Chicago, IL, USA.
authors.forename: Amber N
authors.initials: AN
authors.lastname: Fiutko
authors.affiliation: 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.forename: Elizabeth
authors.initials: E
authors.lastname: Berry-Kravis
authors.affiliation: Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Hall
mesh_terms: D000203:Activities of Daily Living; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001259:Ataxia / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*; D001696:Biomechanical Phenomena; D003201:Computers; D042241:Early Diagnosis; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic / Q000379:methods; D004856:Postural Balance / Q000235:genetics*; D011930:Reaction Time; D012044:Regression Analysis; D014202:Tremor / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*; D019680:Trinucleotide Repeat Expansion
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human
keywords: Balance; Cerebellum; Computerized dynamic posturography; FMR1 premutation carrier; Fragile X mental retardation 1 (FMR1) gene; Fragile X-associated tremor/ataxia syndrome (FXTAS)