Huntington's disease: clinical correlates of disability and progression.
OBJECTIVE
To define the phenotypic variation in a large population of patients with Huntington disease (HD) and to identity clinical features that predict disability and the rate of disease progression.


METHODS
The authors analyzed data on 1,026 patients, followed for a median of 2.7 years, using a mixed effects model. The factors studied included the age at onset, the major clinical feature at onset, the severity of motor and cognitive impairment, and the level of disability.


RESULTS
The mean age at onset was 41.5 (range 8 to 83) years, and patients were enrolled at all stages of disease. Younger onset was associated with more dystonia, less chorea, and a faster rate of motor, cognitive, and functional progression. The rate of progression was not related to the major clinical feature at onset or the sex of the affected parent. Disability correlated with the motor score (excluding chorea and dystonia) and the symbol-digit modalities test. Weight loss correlated with severe chorea.


CONCLUSIONS
The rate of progression of HD was significantly more rapid with a younger age at onset. Therefore, CAG repeat length may be an important determinant of not only the age at onset, but also the rate of disease progression. Chorea was associated with weight loss, but chorea and dystonia were not major determinants of disability.
Department of Neurology, Westmead Hospital, NSW, Australia.
N
N
Mahant
E A
EA
McCusker
K
K
Byth
S
S
Graham
D017668:Age of Onset; D002819:Chorea / Q000175:diagnosis / Q000209:etiology; D003072:Cognition Disorders / Q000175:diagnosis / Q000209:etiology; D004185:Disability Evaluation; D018450:Disease Progression; D004421:Dystonia / Q000175:diagnosis / Q000209:etiology; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012044:Regression Analysis; D019680:Trinucleotide Repeat Expansion