Huntington disease

Huntington disease (HD), also known as Huntington chorea or Huntington's disease, is a progressive neurodegenerative disorder caused by an expanded CAG trinucleotide repeat in the HTT gene on chromosome 4p16.3. This expansion leads to the production of an abnormal huntingtin protein that accumulates in neurons, causing progressive damage primarily to the basal ganglia (especially the caudate nucleus and putamen) and the cerebral cortex. HD affects the nervous system and has profound impacts on motor function, cognition, and psychiatric health. The hallmark motor feature of HD is chorea — involuntary, irregular, dance-like movements that typically begin subtly and progress over time. As the disease advances, patients develop dystonia, rigidity, bradykinesia, difficulty with balance and gait, dysphagia (swallowing difficulties), and dysarthria (slurred speech). Cognitive decline is a core feature, progressing to dementia, and includes impairments in executive function, attention, and processing speed. Psychiatric symptoms are common and often precede motor onset; these include depression, irritability, apathy, anxiety, obsessive-compulsive behaviors, and in some cases psychosis. Weight loss is also a significant clinical feature. HD typically manifests in adulthood, with a mean age of onset between 30 and 50 years, though juvenile-onset forms (Westphal variant) can occur when the CAG repeat length is very large (usually >60 repeats). Normal alleles contain up to 26 CAG repeats, while alleles with 36 or more repeats are considered fully penetrant (40+) or have reduced penetrance (36–39). The disease follows an inexorable course over 15 to 20 years from symptom onset to death. There is currently no cure or disease-modifying therapy for HD. Treatment is symptomatic: tetrabenazine and deutetrabenazine are FDA-approved for chorea management, while antidepressants, antipsychotics, and other medications are used to address psychiatric and behavioral symptoms. Multidisciplinary care including physical therapy, speech therapy, nutritional support, and psychosocial services is essential. Genetic testing and genetic counseling are critically important for at-risk family members, and predictive testing is available for presymptomatic individuals.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Huntington disease