Huntington's disease

Autosomal dominant

1:20,000

Huntington's disease is caused by a triplet repeat mutation resulting in an altered Huntington protein which clumps together inside neuron cells leading to death. This particularly affects neurons in brain areas responsible for mental abilities and movement coordination with the progressive neuronal loss leading to the gradual development of abnormal movements and changes in cognition, behaviour, and personality. A persons’ ability to walk, think, talk and reason slowly diminish. The onset of symptoms is usually between the ages of 30 and 50 and it affects between 1 and 2 in 20,000 individuals.

It was in New York, in 1872, that George Huntington wrote a paper on the chorea emphasizing the hereditary nature of the disorder and providing the first scientific description of the disease. He was only 22 years old at the time! The family he studied were ancestors of a man by the name of Jeffrey Francis who emigrated from England, carrying the Huntington mutated gene, in 1634. This is an example of a ”founder effect” (described in more detail later) which also occurred in South Africa where several hundred people who developed Huntington’s disease were all descendents of a Dutch immigrant called Elsje Cloetens, who arrived there in 1652. Another population with a high incidence of the disease live near Lake Maracaibo in Venezuela and are all related to a Spanish sailor from Hamburg, Antonio Justo Doria, who lived during the 18th century and who travelled to Venezuela to buy dye for a German factory. It was the analysis of shared DNA sequences between these Venezuelan descendents that enabled scientists to ‘map’ the location of the Huntington gene to chromosome 4, by using a process known as Linkage analysis.

In America Huntington’s disease is often referred to as “Woody Guthrie’s disease” from the famous American folk singer who died from it. One day in the 1950s Woody Guthrie’s wife noticed her husband walking lopsidedly. This was soon followed by slurred speech and uncontrollable rages. Eventually, he lost all ability to talk, read, or walk and the only way he could communicate with his wife and children was by waving his arm at cards printed with the words ‘Yes’ and No’. In 1967 he died from the disease, which had previously killed his mother, from whom he had inherited it. This is because the disease is inherited in an autosomal dominant fashion and so a parent with the HD gene has a 50% chance of passing it on to each offspring. When a parent develops symptoms of HD their offspring have to decide whether or not to have themselves tested for the presence of the mutant gene. Should the results prove positive they would live with the certainty of developing symptoms of the disease before the age of 50. Insurance companies now legally have the right to know the outcome of any such test.

Sometimes known as Huntington’s Chorea, this disease has been reported since the 16th century and it was the early Renaissance physician Paracelsus who used the term “chorea” (the Greek word for dance) to describe the shaking and twitching that people with the disease went through. English colonists in America called the disease Saint Vitus Dance (St Vitus is the patron saint of dancers), and many of the "witches" at the infamous Salem Witch Trials of 1692 in Massachusetts, are now believed to have had HD; their choreic movements and odd behaviour were seen as possession by the devil.