Huntington’s disease is caused by a mutation that occurs in the Huntingtin (HTT) gene, which is located on chromosome 4. The mutation exists as an expansion mutation of the trinucelotide cytosine-adenine-guanine (CAG).
The length of this CAG expansion determines the severity and onset of the disease. Generally, the number of CAG repeats accounts for 60% of the variation in how old people are when symptoms start to develop. Factors such as environment and the presence of other genes that contribute to the mechanism of Huntington’s disease are thought to account for the remaining variation. Healthy individuals usually have fewer than 36 repeats. People with 36 to 39 repeats develop a mild form of Huntington’s disease that is associated with a much later disease onset and much slower disease progression. This is referred to as reduced-penetrance Huntington’s disease.
As expanded copies of HTT are passed on through generations, the number of repeats can increase in successive generations causing a more severe disease to occur at an earlier age of onset than in previous generations. This is referred to as genetic anticipation. In around 6% of cases, Huntington’s disease develops in people aged under 21 years. This rapidly progressing form of the condition is referred to as juvenile, akinetic-rigid or Westphal variant HD.
Symptoms vary between individuals but some of the most common earliest symptoms are changes in mood and cognitive function, lack of coordination and an unsteady gait. As the disease progress, movement may become jerky and uncontrolled and a decline in mental ability becomes more obvious, with dementia eventually developing. Most patients eventually require assistance in their day-to-day living, which may take the form of speech therapy to help improve communication or physiotherapy to help improve mobility, for example.
A diagnosis of Huntington’s disease can be very distressing for a patient and their family and friends to receive. Various support groups and counselling/therapy services are available to support such individuals. There is no cure for Huntington’s disease and eventually patients require full-time palliative care. Various medications are available to help relieve symptoms associated with the condition.
Reviewed by Sally Robertson, BSc