Daniel Claassen, MD, MS, provides an overview of the pathophysiology and genetic background of Huntington’s disease (HD), a neurodegenerative disorder.
This is a video synopsis/summary of a discussion involving Daniel Claassen, MD, MS.
Huntington's disease is a neurodegenerative disorder resulting from a mutation in the Huntington gene, characterized by a CAG (cytosine, adenine, guanine) repeat and inherited in an autosomal dominant manner. Typically manifesting in individuals within the age-range of mid-30s or 40s, the initial symptoms include cognitive changes and motor symptoms known as chorea.
Over the last decade, advancements in diagnostics have enabled the identification of individuals with the expanded CAG repeat, allowing for longitudinal monitoring. This has shifted the understanding of when Huntington's disease begins, suggesting it starts earlier than previously thought. By the time chorea appears, cognitive and psychiatric symptoms may already be present.
The disease primarily affects the striatum, the putamen and caudate in particular, leading to atrophy in these areas and subsequent brain atrophy. Huntington's disease presents with a triad of symptoms: motor, cognitive, and psychiatric, along with potential additional symptoms like sleep disturbances.
The discovery of the Huntington gene in 1993 marked a pivotal moment, emphasizing the collaborative nature of research. The Huntington study group, formed 30 years ago, played a crucial role, conducting extensive family histories and linkage studies, particularly in Venezuela.
The genetic aspect involves an expanded repeat disorder, with an autosomal dominant inheritance pattern. Anticipation, observed more in paternal inheritance, results in longer repeats in subsequent generations, contributing to earlier onset and more severe symptoms. The critical threshold for symptom development is often considered to be 40 or more CAG repeats, indicating 100% penetrance for Huntington's disease.
Patients often seek guidance on when to undergo testing, and genetic counselors, along with multidisciplinary teams, play a crucial role in providing support and managing these challenging situations. Overall, understanding the genetic and clinical aspects of Huntington's disease has evolved, emphasizing the importance of collaborative research and multidisciplinary care.
Video synopsis in AI-generated and reviewed by NeurologyLive editorial staff.