Huntington's disease

HD is an adult-onset, autosomal dominant inherited neurodegenerative disorder characterized by the progressive development of chorea, psychiatric symptoms, and cognitive impairment.

Primary neuropathophysiology occurs in the neostriatum with atrophy, neuronal loss and gliosis in the caudate nucleus, thalamus, and, ultimately, the cortex. HD is caused by a cytosine-adenine-guanine (CAG) trinucleotide repeat expansion at the 5' end of the huntingtin gene.

The cumulative incidence rate of HD in the US is estimated at 1.22 per 100,000 persons (95% CI 1.53-1.65). Mean age at onset ranges from 35-44 years.

Initial clinical manifestations include motor dysfunction (chorea, athetosis, oculomotor disorders), hyperreflexia and hyperhidrosis. Advanced stages progress to movement dysfunction (dystonia, rigidity, bradykinesia, dysarthria, gait disturbance, facial grimacing), cognitive decline (dementia), and psychiatric disturbances (major depressive disorder, psychosis, obsessive-compulsive symptoms, suicidal ideation). Additionally, ataxic gait and seizure may occur.

Huntington disease progresses to disability, and eventually death approximately 15-20 years after onset. Intercurrent illnesses such as aspiration pneumonia are the most common cause of death.