Comparison of the Clinical Spectrum of Juvenile- and Adult-Onset Huntington Disease: A National Cohort and Enroll-HD Observational Study.

BACKGROUND AND

OBJECTIVES

Differences in clinical characteristics between juvenile-onset Huntington disease (JHD) and adult-onset HD (AHD) are hypothesized but not directly compared. This study compares clinical characteristics occurrence and severity across age-at-onset (AO) subtypes.

METHODS

Using the national juvenile-onset HD patient cohort and the international Enroll-HD registry (NCT01574053), we compared childhood-onset JHD (cJHD; AO 0-10), adolescent-onset JHD (aJHD; AO 11-20), and adult-onset HD (AHD; AO 21-65) on proportions of clinical characteristics at onset and psychiatric characteristics in pooled datasets. Kruskal-Wallis test was applied to UHDRS-Total Motor Score (UHDRS-TMS) items of the Enroll-HD dataset to compare the severity of motor disease characteristics 6-10 years after onset.

RESULTS

The combined datasets provided data from 46 patients with cJHD (mean AO 6.70, 45% female), 243 patients with aJHD (mean AO 16.70, 46% female), and 9,504 patients with AHD (mean AO 44.70, 51% female). At onset, neurocognitive symptoms occurred in 47.50% of patients with cJHD (n = 46; 95% CI 31.80%-63.70%), significantly more often compared with 24.88% of patients with aJHD (n = 209; 19.30%-31.40%) and 15.02% of those with AHD (n = 8,177; 14.30%-15.80%). Psychiatric symptoms occurred in 47.12% of patients with aJHD (95% CI 40.20%-54.10%), significantly more compared with 31.04% of patients with AHD (30.10%-32.00%). Throughout the disease, aggressive behavior occurred in 73.91% of patients with cJHD (n = 46; 95% CI 58.60%-85.20%) and 55.88% of those with aJHD (n = 238; 49.30%-62.30%), significantly more compared with 40.65% of patients with AHD (n = 9,501; 39.70%-41.70%). Psychosis occurred in 23.53% of patients with aJHD (95% CI 18.40%-29.50%), significantly more compared with 12.77% of those with AHD (12.10%-13.50%). The Kruskal-Wallis test revealed significantly higher median UHDRS-TMS scores in one or both JHD subtypes compared with AHD for dysarthria (AHD: n = 4,163, median 1.00, interquartile range (IQR) 0.70; cJHD: n = 12, 2.20, 2.00, p = 0.039; aJHD: n = 93, 1.00, 1.00, p = 0.031), parkinsonism (AHD: n = 4,158, median 6.00, IQR 4.70; cJHD: n = 12, 11.00, 9.40, p = 0.008; aJHD: n = 93, 8.50, 6.80, p < 0.001), and dystonia (AHD: n = 4,161, median 2.00, IQR 5.20; cJHD: n = 12, 6.50, 8.20, p = 0.141; aJHD: n = 93, 4.00, 7.20, p = 0.015) and significantly lower median scores for chorea (AHD: n = 4,163, median 9.20, IQR 7.00; cJHD: n = 12, 5.00, 4.20, p = <0.001; aJHD: n = 93, 6.30, 9.50, p < 0.001).

DISCUSSION: This study highlights distinct clinical patterns in JHD subtypes compared with AHD. Stratification by age at onset-defined HD subtypes is needed in future studies.