Behavioral Deficits in Juvenile Onset Huntington’s Disease

Abstract

Reports of behavioral disturbance in Juvenile-Onset Huntington’s Disease (JOHD) have been based primarily on qualitative caregiver reports or retrospective medical record reviews. This study aims to quantify differences in behavior in patients with JOHD using informant- and self-report questionnaires. Informants of 21 children/young adults (12 female) with JOHD and 115 children/young adults (64 female) with a family history of Huntington’s Disease, but who did not inherit the disease themselves (Gene-Non-Expanded; GNE) completed the Behavior Rating Inventory of Executive Function (BRIEF) and the Pediatric Behavior Scale (PBS). Mixed linear regression models (age/sex adjusted) were conducted to assess group differences on these measures. The JOHD group had significantly higher scores, indicating more problems, than the GNE group on all BRIEF subscales, and measures of Aggression/Opposition and Hyperactivity/Inattention of the PBS (all p < 0.05). There were no group differences in Depression/Anxiety. Inhibit, Plan/Organize, Initiate, and Aggression/Opposition had significant negative correlations with Cytosine-Adenine-Guanine (CAG) repeat length (all p < 0.05) meaning that individuals with higher CAG repeats scored lower on these measures. There was greater discrepancy between higher informant-vs. lower self-reported scores in the JOHD group, supporting the notion of lack of insight for the JOHD-affected group. These results provide quantitative evidence of behavioral characteristics of JOHD.

“Spazio Huntington”: Tracing the Early Motor, Cognitive and Behavioral Profiles of Kids with Proven Pediatric Huntington Disease and Expanded Mutations > 80 CAG Repeats

“…Among the peculiarities we highlight in our study, we describe and confirm the high occurrence of sleep disorders in affected young children, in line with previous reports on JOHD [14]. We also confirm the occurrence of seizures as a common feature in PHD [8,[31][32][33]. Furthermore, we report the occurrence of drooling, dysphagia, stereotypic movements and apraxia during the first phases of the disease, all features that may concur to worsen the disease severity and shorten the patients' life span, as described [8].…”

“…So far, all studies concerning cognitive and behavioral changes in PHD cohorts have been performed by caregiver-based, self-reported, retrospective descriptions, with no focus on specific and comprehensive evaluations [8,9,16] or by caregiver survey [14,31]. Few studies reported a retrospective analysis in JOHD with neuropsychological examinations only performed in young adults (i.e., aged 20 years) and almost never in affected kids, generally showing limited length mutations [15,16].…”

Unraveling the role of relative telomere length and CAG expansion on initial symptoms of juvenile Huntington disease

“…The recognition of the first symptom is a challenging task even in cases with a family history of HD; the delay has been reported to be up to 9 years. Our results reinforce the relevance of the cognitive and psychiatric symptoms in patients with JHD, unlike adult HD; these clinical manifestations need to be investigated in more detail to avoid diagnosis delay [39].…”

Tracking Huntingtonʼs Disease Progression Using Motor, Functional, Cognitive, and Imaging Markers

“…This may suggest that to identify subtle deviations between different disease epochs above and beyond already established knowledge, collecting continuous longitudinal data for longer periods and with more times per participant (eg, collecting annual data for >10 years) is required. This, also together with other factors including follow‐up of younger, more diverse samples, 40,41 could be argued as being more important than having a bigger sample with follow‐up of 4–5 years. This further supports previous discussions on the importance of investing in long‐term longitudinal studies that span 5 years or more with annual follow‐up, which has been posited for HD 42,43 as well as other neurodegenerative diseases like Alzheimerʼs disease 44,45 .…”