Epidemiology of Huntington disease

Abstract

Huntington disease (HD) is an autosomal-dominant neurologic disorder caused by an expanded CAG trinucleotide repeat mutation in patients with characteristic motor signs and specific brain pathology. A repeat of 36 CAG or more can lead to the disease, with increased penetrance and decreased age of onset at longer CAG repeats. The epidemiology of HD thus depends on ascertainment of individuals with the expanded CAG mutation, and on examination of clinical signs to accurately assess disease onset. A larger number of individuals have an expanded CAG repeat than actively manifest the disease due to adult onset in the majority of cases. Because of incomplete penetrance at the lower end of the pathogenic CAG repeat range, the frequency of the expanded CAG repeat in the general population may be higher than previously thought. Genetic differences and changing demographics may account for geographic and ethnic variation in the prevalence of HD between populations and over time. There are gross differences in the prevalence of HD by ancestry, with a much higher rate of the disease in populations of European descent. Molecular studies have elucidated genetic causes for these population-specific differences, possibly resulting from differences in the HD new mutation rate.

Keywords: Huntington disease; de novo mutation; epidemiology; genetic testing; genetics; haplotypes; neurodegeneration; penetrance; prevalence; trinucleotide repeat.