Ameliorating the age at onset and disease progression in Huntington disease

Huntington disease (HD) is a relentlessly progressive neurogenetic disorder with classic clinical features including choreiform movements, mood swings, memory impairment, and weight loss. In affected individuals, the huntingtin (HTT) gene contains a triplet repeat CAG expansion. The age at onset (Ao) of HD symptoms is inversely correlated with CAG repeat size 1,2-the larger the expansion, generally the more severe and earlier the onset of symptoms. Approximately two-thirds of the Ao etiology is attributed to the CAG expansion size, but onset of symptoms is also determined by the unexpanded CAG repeat length in HTT, and other mostly unknown modifier genes (a contribution of about 10%-15%) and by environmental factors (about 10%). 2,3 What is less clear, however, is whether the factors determining Ao also govern disease progression. © 2018 American Academy of Neurology.