Huntington Disease

Huntington disease is an autosomal dominant neurodegenerative disorder caused by expansion of a CAG trinucleotide repeat in the huntingtin gene, resulting in production of an abnormal huntingtin protein that accumulates and damages neurons, particularly in the basal ganglia and cortex. The number of CAG repeats correlates inversely with age of onset; longer repeats cause earlier disease manifestation. The disease progresses relentlessly, causing progressive movement disorders (chorea, dystonia, rigidity), cognitive decline, and psychiatric manifestations. While the disease typically manifests in the third to fifth decade with a mix of hyperkinetic (excessive involuntary movement) and hypokinetic (slow, restricted movement) features, juvenile-onset disease (before age 20) often presents with more rigidity and psychiatric features. There is currently no cure for Huntington disease, but several disease-modifying therapies targeting mutant huntingtin protein (including huntingtin-lowering strategies) are in advanced clinical trials.