Huntington Disease: The ‘typical’ phenotype for the commonest CAG repeat expansion in the ENROLL-HD study (P4.041)

Objective: To explore the Huntington disease (HD) phenotype for the commonest CAG repeat. Background: An absolute constant in HD is the variable CAG repeat expansion in the Huntingtin gene. Much is known about the variation in onset of motor manifestations and the inverse relationship to the expansion length. The wider phenotype including non-motor features at a particular repeat expansion length is less well known, especially at the commoner repeat expansion lengths in a large HD population and at varying functional levels. Design/Methods: Using the ENROLL-HD data base we examined demographic and clinical data for participants with the commonest CAG repeat expansion of 42. The phenotypic profile was documented at different functional levels using the Independence Scale score (ISS) of the Unified Huntington Disease Rating Scale (UHDRS):100, 080, 050, 030 and below. We used SPSS 23 program for descriptive statistics, expressed as median±interquartile range (range). Results: There were 1142 participants of 56±17 (19–91) years old. ISS was 85±30% (0–100%). 35.9% were employed; 70.2% were in a partnership or married; 24.6% had a previous suicide attempt; 75.4% were motor-manifest participants and motor subsection of UHDRS was 25±37 (0–104) in whom all had chorea and 58.3% had dystonia. The median age of symptom onset (range;%) was depression at 48±18 years (2–72;61.3%), irritability at 51±17 years (10–73;57.2%), motor at 52±11 years (0–82;59.4%), aggression at 52±19 years (0–83;26.9%), apathy at 54±14 years (6–83;48.5%), psychosis at 54±17 years (0–72;8.5%), cognitive impairment at 54±11 years (0–80;45.8%) and perseveration at 55±13 years (8–83;39.2%). Symbol digit modality test score was 29±28 (0–101) and MMSE score 28±4 (0–30). Conclusions: This examination of the HD phenotype found that non-motor manifestations were common and associated with the commonest repeat expansion length. This data allows detailed identification of a “typical” HD profile and those with phenotypic variation, enabling identification of disease modifiers. Study Supported by: ENROLL-HD is a longitudinal observation studies for families with HD intended to accelerate progress towards therapeutics; it is sponsored by the CHDI Foundation, a nonprofit biomedical research organisation exclusively dedicated to developing therapeutics for HD. Disclosure: Dr. Chang has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Abbvie. Dr. McCusker has nothing to disclose. Dr. Loy has nothing to disclose.