title: Progression of tremor and ataxia in male carriers of the FMR1 premutation.
abstract: Premutation alleles of the fragile X mental retardation 1 (FMR1) gene give rise to a late-onset movement disorder, fragile X-associated tremor/ataxia syndrome (FXTAS), characterized by progressive intention tremor and gait ataxia, with associated dementia and global brain atrophy. The natural history of FXTAS is largely unknown. To address this issue, a family-based, retrospective, longitudinal study was conducted with a cohort of 55 male premutation carriers. Analysis of the progression of the major motor signs of FXTAS, tremor and ataxia, shows that tremor usually occurs first, with median onset at approximately 60 years of age. From the onset of the initial motor sign, median delay of onset of ataxia was 2 years; onset of falls, 6 years; dependence on a walking aid, 15 years; and death, 21 years. Preliminary data on life expectancy are variable, with a range from 5 to 25 years.
authors.affiliation: Department of Neurology, University of Colorado at Denver and Health Sciences Center, Denver, Colorado 80262, USA. maureen.leehey@uchsc.edu
authors.forename: Maureen A
authors.initials: MA
authors.lastname: Leehey
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Berry-Kravis
authors.forename: Sung-Joon
authors.initials: SJ
authors.lastname: Min
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Hall
authors.forename: Cathlin D
authors.initials: CD
authors.lastname: Rice
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Jim
authors.initials: J
authors.lastname: Grigsby
authors.forename: Claudia M
authors.initials: CM
authors.lastname: Greco
authors.forename: Ann
authors.initials: A
authors.lastname: Reynolds
authors.forename: Rebecca
authors.initials: R
authors.lastname: Lara
authors.forename: Jennifer
authors.initials: J
authors.lastname: Cogswell
authors.forename: Sebastien
authors.initials: S
authors.lastname: Jacquemont
authors.forename: David R
authors.initials: DR
authors.lastname: Hessl
authors.forename: Flora
authors.initials: F
authors.lastname: Tassone
authors.forename: Randi
authors.initials: R
authors.lastname: Hagerman
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Hagerman
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D001259:Ataxia / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology*; D041321:Chromosomes, Human, X / Q000235:genetics; D018450:Disease Progression; D005500:Follow-Up Studies; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics / Q000502:physiology*; D020868:Gene Silencing / Q000502:physiology; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation / Q000235:genetics*; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013997:Time Factors; D014202:Tremor / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology*
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human