Huntington disease

Huntington disease (HD) is an inherited progressive disorder of the brain that blends movement difficulties with changes in thinking and behavior. It results from a CAG repeat expansion in the HTT gene that causes production of a toxic form of the huntingtin protein, leading to gradual loss of nerve cells. Symptoms usually begin in mid-adulthood but can appear in childhood or later life, affecting people of all sexes. HD affects approximately 3 to 7 out of every 100,000 people of European descent, placing it in the uncommon range worldwide.

The hallmark of HD is progressive chorea, dance-like involuntary movements that often start subtly in the fingers, face, or walking pattern. Early features can include clumsiness, gait imbalance, or slowed eye movements together with mood or personality changes such as irritability, anxiety, depression, or disinhibition that may precede obvious motor problems. As the condition advances, many people experience worsening chorea, periods of hypokinesia or bradykinesia, dystonia, generalized muscle weakness, and difficulty with coordination and speech. Thinking becomes slower, short-term memory declines, and psychiatric manifestations such as apathy, agitation, compulsive behaviors, hallucinations, or delusions may appear. Seizures occur in a minority, and unintentional weight loss is common despite adequate intake. Not all individuals experience every feature, and severity and rate of progression vary widely.

HD is a repeat expansion disorder caused by an abnormal increase in the number of CAG repeats in the HTT gene. Normal alleles have fewer than 27 repeats, while alleles with 40 or more repeats invariably lead to disease; longer expansions usually bring earlier onset. Because the repeat length can increase when passed to the next generation, especially from an affected father, successive generations may develop symptoms at younger ages, a phenomenon called anticipation. The condition is inherited in an autosomal dominant pattern, meaning one altered copy of HTT is sufficient to cause HD and each child of an affected parent has a 50 percent chance of inheriting the expansion. Approximately eight percent of cases arise de novo through expansion of an intermediate allele, so a person can be the first in a family to be affected. Genetic counseling is strongly recommended for affected individuals and their relatives.

Current care focuses on relieving symptoms and preserving function. Tetrabenazine or deutetrabenazine can reduce chorea, while antidepressants, antipsychotics, or mood-stabilizing medications address depression, anxiety, agitation, or compulsive behavior. Physical therapy helps maintain balance and mobility, speech and swallowing therapy support communication and safe eating, and high-calorie nutrition plans counteract weight loss. Care is best delivered by a multidisciplinary team that commonly includes a neurologist, psychiatrist, genetic counselor, physical and speech therapists, and a social worker. In addition to treating active symptoms, ongoing surveillance through regular neurologic and psychiatric assessments, swallowing evaluations, and fall-risk screening helps detect complications early. Genetic counseling provides guidance on family planning, predictive testing, and psychosocial support. At present no therapies are specifically approved by the U.S. Food and Drug Administration to alter disease progression, but supportive interventions can markedly improve quality of life.

HD is lifelong and progressive, but its course is highly variable. Age of onset, the mix of motor versus psychiatric features, and the tempo of decline differ even among family members. With coordinated multidisciplinary care, many individuals live for decades after symptoms first appear, although increasing movement difficulties and cognitive changes eventually necessitate substantial assistance with daily activities. Advances in symptomatic therapies, assistive technology, and community support are helping many families maintain independence and quality of life for longer periods.

HD is the focus of active research worldwide, with numerous ongoing clinical trials exploring ways to lower or silence the mutant huntingtin protein, apply RNA interference or gene-editing technologies, and protect vulnerable neurons. Individuals interested in clinical trials can search ClinicalTrials.gov or discuss emerging studies and eligibility with their healthcare team.