Current knowledge of Huntington's disease-like 2 genetic testing, clinical presentation, and patient experiences: A systematic review
- Author(s)
- Hoffmann, K; White, S; Sexton, A;
- Journal Title
- Journal of Huntington's Disease
- Publication Type
- Online publication before print
- Abstract
- 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.; Huntington's Disease-like 2 (HDL2) is a rare condition that can look very similar to Huntington's Disease (HD), which often makes it hard to diagnose. People who have symptoms like those seen in HD but test negative for HD may have HDL2 instead. This paper adds a new depth compared to a previous overview on HDL2 by Krause and co-authors in 2024.(1) Here, we have used systematic methods to look at all the available research on HDL2 to better understand the condition and to help doctors and genetic counsellors support individuals and families affected by it. We searched four major research databases and found 36 relevant studies including 109 people with HDL2. Most of these focused on the medical and genetic features of people with HDL2. However, we found very little research on how to support people living with the condition or how to provide genetic counselling to families at risk. The main findings included information about how the condition is inherited, the role of African ancestry, symptoms that often appear early (especially psychiatric symptoms), and the length of time people have the condition for. Our review shows that more research is needed on how to support people with HDL2 and their families. Understanding early symptoms involved can help improve diagnosis and counselling. In the meantime, adapting support approaches used for Huntington's Disease may be helpful.; eng
- Keywords
- Huntington disease-like 2; chorea; cognition disorders; dementia; diagnosis; genetic counselling; genetic testing; neurodegenerative disorders
- Department(s)
- Familial Cancer Centre
- Publisher's Version
- https://doi.org/10.1177/18796397251411109
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2026-01-29 05:40:52
Last Modified: 2026-01-29 05:40:57