A – 122 The Impact of Mood in HD in Siblings with Genetically Confirmed Huntington’s Disease

Abstract Objective Huntington's disease (HD) is an autosomal dominant progressive neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms. We present two siblings with genetically confirmed HD who reported cognitive concerns. Method Two siblings, Patient A (PtA, 51-year-old female) and Patient B (PtB, 45-year-old male), reported onset of cognitive symptoms 3 (PtA) and 5 (PtB) years prior to evaluation. Presenting symptoms included word-finding difficulties, inattention, decline in reading retention and comprehension, slowed thinking, forgetfulness, and spatial disorientation. PtB additionally noted multitasking difficulties and misplacing objects. Genetic testing revealed identical CAG repeats lengths (41/16 for both). Results PtA exhibited low average performance on phonemic fluency (FAS T=39) and figure copy (Benson Figure Copy T=36) and reported significant emotional distress (BDI-II=42, BAI=46). PtB demonstrated exceptionally low nonverbal encoding (BVMT-R-Total Recall T=23), while below average for reproduction of a complex design He was diagnosed with persistent depressive disorder (BDI-II=34, BAI=21), which emerged post-HD diagnosis, and reported distress related to caregiving for a family member with HD. Despite both patients endorsing elevated scores on BDI-II and BAI, their symptomatology differed. Conclusion Despite identical CAG repeats and environmental backgrounds, PtA and PtB presented with markedly different cognitive and emotional profiles. These phenotypic differences highlight the variability in clinical manifestation even among siblings raised together. This underscores the importance of utilizing a comprehensive neuropsychological battery evaluating cognitive and emotional presentations is essential to capture the nuanced phenotypic variability in HD, allowing for more personalized and timely interventions.