Functional status of men with the fragile X premutation, with and without the tremor/ataxia syndrome (FXTAS).
BACKGROUND
Fragile X-associated tremor/ataxia syndrome (FXTAS), which occurs in some premutation carriers of the fragile X mental retardation 1 (FMR1) gene, is a neurodegenerative disorder characterized by action tremor, gait ataxia, and impaired executive cognitive functioning.


OBJECTIVE
To evaluate the nature and severity of functional limitations among male carriers of the fragile X premutation, both with and without FXTAS.


METHODS
Forty-two subjects with FXTAS and 24 asymptomatic premutation carriers were compared to 32 control subjects on measures of physical functioning, activities of daily living (ADLs; e.g. eating, bathing), and instrumental activities of daily living (IADLs; e.g. shopping, managing medications). Ordinary least squares regression, controlling for age, education, medical comorbidity, and pain, was used to examine group differences in physical and functional performance.


RESULTS
Men with FXTAS performed significantly worse than control subjects on all dependent measures, showing greater limitations in physical functioning, as well as ADL and IADL performance (p < 0.05). Subsequent analyses suggested that physical and functional impairments among men with FXTAS result largely from deficits in motor and executive functioning and that CGG repeat length is associated with functional impairment. Asymptomatic carriers of the fragile X premutation performed similarly to control subjects on all measures.


CONCLUSIONS
This study provides the first comprehensive evaluation of functional status among male premutation carriers. Although carriers without FXTAS performed similarly to control subjects, men with FXTAS showed evidence of significant physical and functional impairment, which appears to result largely from motor and executive deficits characteristic of the syndrome.
Brega
Angela G
AG
Department of Medicine, University of Colorado Denver, Aurora, CO 80217-3364, USA.
Reynolds
Ann
A
Bennett
Rachael E
RE
Leehey
Maureen A
MA
Bounds
Lanee S
LS
Cogswell
Jennifer B
JB
Hagerman
Randi J
RJ
Hagerman
Paul J
PJ
Grigsby
Jim
J
D000203:Activities of Daily Living; D000368:Aged; D000369:Aged, 80 and over; D001259:Ataxia / Q000150:complications* / Q000235:genetics; D003072:Cognition Disorders / Q000209:etiology / Q000503:physiopathology; D004185:Disability Evaluation; D056344:Executive Function / Q000502:physiology*; D005600:Fragile X Syndrome / Q000150:complications* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009043:Motor Activity / Q000502:physiology; D009483:Neuropsychological Tests; D012044:Regression Analysis; D014202:Tremor / Q000150:complications* / Q000235:genetics