Huntington's Disease

An inherited disease caused by a repeated stretch of DNA in one gene: involuntary movements, psychiatric and cognitive changes, the Venezuelan families who helped find the gene, genetic testing dilemmas and the hunt for treatments.

George Huntington's description

In 1872 the 22-year-old American physician George Huntington, drawing on families his father and grandfather had treated on Long Island, published a clear description of a hereditary "chorea" — from the Greek for dance — beginning in adult life and steadily progressing, with a tendency to insanity.

The genetics

Huntington's disease (HD) is autosomal dominant: one copy of the faulty gene is enough, so each child of an affected parent has a 50% chance of inheriting it. The gene, HTT, contains a repeated sequence of three DNA letters, CAG. Most people have fewer than about 27 repeats; 40 or more cause the disease (36–39 may or may not). Longer repeats usually mean earlier onset, and repeats can lengthen when passed on — especially from fathers — so the disease can begin earlier in successive generations.

Finding the gene

The search was driven by Nancy Wexler, whose mother had HD. From 1979 she led expeditions to villages around Lake Maracaibo in Venezuela, home to an extended family with very high rates of HD, collecting blood samples and building a family tree of thousands of people. In 1983 the gene was mapped to chromosome 4, and in 1993 a large collaboration identified it.

Symptoms

Symptoms typically start between 30 and 50. Movement: involuntary, jerky, dance-like movements (chorea), clumsiness, and later stiffness and swallowing problems. Psychiatric: depression, irritability, apathy and sometimes obsessive behaviour, often appearing years before movement problems. Cognitive: slowed thinking, difficulty planning and multitasking. The disease progresses over about 15–20 years. Early damage is concentrated in the striatum of the basal ganglia.

Testing and treatment

Predictive genetic testing has been available since 1993; many at-risk people choose not to be tested, given there's no cure, and those who do receive careful counselling. Current treatments manage symptoms — for example, tetrabenazine for chorea. Several strategies aim to lower production of the huntingtin protein; an antisense drug, tominersen, had a disappointing large trial in 2021. In 2025, a small trial of an experimental gene therapy (AMT-130) reported early results suggesting slower progression; larger confirmation is needed.