Huntington’s Disorders

Huntington’s disease (HD) is the most common genetic cause of a specific type of involuntary limb movements called chorea (from the Ancient Greek word ‘choreia’, meaning “dance”).  Hence the disease was originally called Huntington’s chorea.

The disease is more common in people of Western European descent, compared to those of Asian or African ancestry, and affects both men and women. It is caused by an autosomal dominant mutation in either of an individual’s two copies of the Huntingtin gene, meaning that any offspring of an affected parent carries a 50% chance of inheriting the disease. The Huntingtin gene encodes the protein, huntingtin, with the abnormal gene in affected individuals producing an abnormal form of the protein that gradually builds up and causes loss of nerve cells in various parts of the brain.

Physical symptoms of HD can develop at any age from infancy to old age, but do not usually begin until the third or fourth decades of life. This means that affected individuals may already have passed on the disease to their children before they develop the first symptoms of the disease themselves. Genetic testing and appropriate counselling of individuals from families known to have the HD gene is therefore of paramount importance.

Symptoms of the disease often vary between individuals and even among affected members of the same family. The earliest symptoms are often subtle problems with mood or mental functions. Development of chorea and impaired coordination and an unsteady gait usually follow. As the disease advances, uncoordinated, jerky body movements become more prominent, along with a progressive decline in mental abilities and behavioural and psychiatric problems, eventually leading to dementia.

Finding a cure for HD is a major challenge and intensive research is underway to develop drugs that will inhibit the production of the mutant huntingtin protein in the brain.  Clinical trials of antisense oligonucleotides (ASON), that have been shown to be effective in animal models of HD, are currently in progress.

A number of other genetic disorders with chorea and features resembling HD (e.g. HDL-1, HDL-2, HDL-4 etc) are now recognised.  These conditions are caused by mutations in other genes and it is important that they are distinguished from HD by genetic testing, as the course of the disease and prognosis may be different.