Progression of tremor and ataxia in male carriers of the FMR1 premutation.
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.
Leehey
Maureen A
MA
Department of Neurology, University of Colorado at Denver and Health Sciences Center, Denver, Colorado 80262, USA. maureen.leehey@uchsc.edu
Berry-Kravis
Elizabeth
E
Min
Sung-Joon
SJ
Hall
Deborah A
DA
Rice
Cathlin D
CD
Zhang
Lin
L
Grigsby
Jim
J
Greco
Claudia M
CM
Reynolds
Ann
A
Lara
Rebecca
R
Cogswell
Jennifer
J
Jacquemont
Sebastien
S
Hessl
David R
DR
Tassone
Flora
F
Hagerman
Randi
R
Hagerman
Paul J
PJ
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*
D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human