The Clinical Features and Progression of Late-Onset Versus Younger-Onset in an Adult Cohort of Huntington’s Disease Patients

Abstract

Background: Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder that typically manifests between the ages of 30 and 50 years. However, the disease can present at any age, and phenotypic differences between younger and later-onset patients have received limited attention. Objective: To compare clinical features of late- (>70 years of age) and younger-onset (<30 years of age) HD patients. Methods: Patients presenting to our regional NHS HD clinic with new-onset manifest HD diagnosed over the age of 70 years (LoHD) (n = 18) were compared with a younger cohort who developed disease under the age of 30 years (YoHD) (n = 12). Rate of progression over time on standard cognitive and motor measures was compared. Results: At first clinic presentation, both groups had the same total UHDRS scores. However, the LoHD group had higher chorea scores (F (1,28) = 6.52, p = 0.016), while the YoHD group had more dystonia (F (1,28) = 8.69, p = 0.006) and eye movement abnormalities (F (1,28) = 16.991, p < 0.001). The YoHD group also had a greater rate of motor progression, especially for bulbar measures (F (1, 28) = 6.96, p = 0.013) and bradykinesia (F (1, 28) = 7.99, p = 0.009). No differences were found in the rate of cognitive change (F (1,21) = 1.727, p = 0.203) nor functional capacity (F (1,28) = 1.388, p = 0.249) between the groups. Conclusion: Phenotypic differences between YoHD and LoHD patients were found in terms of initial presentation and rate of motor progression. This has implications for therapeutic trials involving HD patients of different ages, given their different clinical features and progression.