The diagnosis and natural history of Huntington disease.

Huntington disease (HD) is an autosomal-dominant disorder resulting from CAG triplet repeats, which leads to an expanded polyglutamine sequence in the HTT (Huntingtin) protein. Accumulation of the Huntingtin protein ultimately leads to neurodegeneration and negative effects in multiple clinical domains, including motor function, cognition, and behavior. HD is a disorder governed by genetics, and the ability to quantify the CAG triplet repeats can provide important insight regarding clinical onset, severity, and disease progression. HD affects generations of family members and can typically span several decades. Understanding HD is invaluable for the advancement in therapeutics for other prevalent neurodegenerative disorders caused by the accumulation of misfolded proteins such as Parkinson disease, Alzheimer disease, and Lewy body dementia.