The Historical and Genetic Evolution of Juvenile Huntington’s Disease

It has been 152 years since George Huntington, a 22-year-old medical school graduate, published his first paper about his observations, “On Chorea.” George Huntington may have been young, but as the grandchild of multi-generational hometown doctors, he witnessed many family discussions regarding a “curious” commonality of symptoms presented by patients who were also multi-generational family members. These symptoms within families ranged from involuntary movements to horrific delusions that became progressively worse, resulting in death. As the understanding of Huntington’s Disease (HD) evolved, so did its genetic mutations making it the first identified genetic disease. We discuss the origin and discovery of HD, its historical evolution from one of the first paper published on HR, to the myths of the Salem Witch Trials, to the Venezuela project, onto the discovery of its genetic source as a CAG repeat on the short arm of chromosome 4. This continued repeat can lead to a rare form of HD, Juvenile Huntington’s Disease (JHD) which accounts for 5-10% of HD. The concluding discussion focuses on current research regarding the CAG repeats and its inverse relationship between the number of mutations and the age of JHD onset, the severity of neurodegeneration in select basal ganglia and cortical regions, and its impact on the timeline and progression of the disease, correlating early signs and lifespan. Kean University This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.