Current knowledge of Huntington's disease-like 2 genetic testing, clinical presentation, and patient experiences: A systematic review

BackgroundHuntington's Disease-like 2 (HDL2) presents complexities in diagnosis due to its similarity to Huntington's Disease (HD). Limited research highlights gaps in knowledge about management and genetic counselling for the condition. HDL2 is rare but an important differential diagnosis for individuals with HD-like symptoms who have tested negative for HD.ObjectiveThis review aimed to synthesise published clinical and genetic data on HDL2, identify knowledge gaps, and serve as a resource for healthcare professionals supporting individuals affected by or at risk of HDL2.MethodsA mixed method integrative systematic review of four databases (Medline, Embase, Scopus, and PsycINFO) generated 323 peer-reviewed articles, of which 36 were included. Data about clinical features, genetic testing and counselling, and patient experiences were interpreted via narrative synthesis.ResultsThe majority of included studies explored the clinical features, genetic testing results and medical histories of individuals with HDL2. A total of 109 people with HDL2 were reported. Limited data was obtained about genetic counselling, management and support, and experiences of those with HDL2 and their families. Findings related to seven categories: DNA repeat length and impact on phenotype, age of onset and disease duration, family history, African ancestry, neurological characteristics, clinical characteristics, and experiences and support.ConclusionsThis review highlights the importance of understanding the reduced penetrance range and early psychiatric symptoms in HDL2 for accurate genetic counselling and interpretation of test results. Adapting existing protocols for HD and qualitatively collecting patient experiences can inform the development of a HDL2 genetic testing and counselling protocol.