The influence of gender on phenotype and disease progression in patients with Huntington's disease.

INTRODUCTION

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder. The aim of this study is to determine whether gender plays a role in the phenotypic expression and progression of HD.

METHODS

1267 patients with HD (636 women) from the Registry project of the EHDN were included. A cross-sectional analysis (ANCOVA) controlling for differences in age at onset, disease burden, disease duration, smoking status, alcohol abuse, depression and the number of years of education, was performed to evaluate if there were differences between men and women in UHDRS motor, function and cognitive scores. Additionally, analyses on follow-up data using linear mixed models with the same covariates were performed to test for gender-related differences in progression.

RESULTS

Baseline features did not differ between genders, with the exception of a higher frequency of past and current depression among women, and a higher number of years of education as well as more frequent alcohol abuse and smoking among men. In the cross-sectional ANCOVA analyses of patients with a mid-age HD onset, women showed worse scores than men in the functional domain (TFC, P = 0.001; UHDRS functional, P = 0.033), UHDRS motor (P = 0.033). The longitudinal analyses showed a faster rate of progression in women in the functional assessment (P = 0.025), the motor assessment (P = 0.032) and the independence scale (P = 0.008).

CONCLUSIONS

These results suggest a complex gender effect on the phenotypical presentation and the rate of disease progression in HD, with slightly more severe phenotype and faster rate of progression in women in especially the motor and functional domains.