Huntington's disease (often abbreviated "HD") was first described in medical literature in 1872 by Dr George Huntington, a physician from Long Island, New York. The disease affects men and women alike, occurring throughout the world. The prevalence is about 7-10 per 100,000 in people of European ancestry, however it can be less or greater in other countries.
Huntington’s disease is a progressive neurological disease. As it is an inherited condition, there are often several people in a family with HD. Symptoms commonly begin between 35 and 44 years but can be earlier or later. It can begin in childhood but that is rarely seen in Australia.
Symptoms fall into 3 main categories: cognitive, motor and psychological:
The extent to which an individual experiences these symptoms varies considerably, even in members of the same family. In other words, each person with HD is unique and one size does not fit all.
Early symptoms may include subtle changes in coordination, perhaps some involuntary movements, difficulty thinking through problems and often a depressed or irritable mood. The person may be less able to carry out their work at their customary level.
With time, the involuntary movements may increase and make leisure and daily living activities such as showering and dressing more difficult. Neurologists (doctors who specialize in brain disorders) may prescribe medication to help reduce the movements. Occupational and physical therapists help with practical management of the motor disturbances and involuntary movements. Psychologists and psychiatrists help the person deal with changes in thinking and reasoning abilities and with emotional and behavioural issues. Medication for significant psychological difficulties can be prescribed. Diminished speech and difficulty swallowing may require help from a speech pathologist.
In due course, the risk of choking on food and drink can become a major concern. Chorea may become more severe or it may lessen or cease altogether. The person with HD loses the ability to eat, walk and speak and becomes dependent on others for their care. Importantly, he or she is still able to comprehend language and retains awareness of their family and friends and their surroundings. When a person with HD dies, it is typically from complications of the disease. Death often occurs 15-20 years after symptoms begin.
HD is caused by a fault in a gene which has the name huntingtin or HTT. Each child of a person with HD has a 1 in 2 (50%) chance of inheriting the gene fault and if they do, they will develop HD in the future. HD is equally likely to occur in males and females.
We all carry two copies of the HTT gene because we inherit one copy from our mother and one from our father. A person with HD has a fault in one copy of their HTT gene.
Most genes don’t change when passed from a parent to a child. The HTT gene is unusual in that the faulty version of the gene can change when passed from a parent with HD to their child, and if so, the effect is stronger in the child. This can make the age at which symptoms first appear in the child sooner than it was in the parent.
In some families, it appears that a person with HD is the first person in the family to have HD. This can be because the parent was not diagnosed with HD or was misdiagnosed with another disease, or perhaps had died prematurely before developing symptoms. But there can also be a genetic reason. If we could do a genetic test on their parents, we will find that one of them carries a mild fault in the HTT gene but they did not develop HD. When they had the child, the gene changed and had a stronger effect in the child who now shows symptoms of HD.
For people who would like to know more about the genetics of HD, please read on!
Genes are like books written in an alphabet of 4 letters: C, A, G and T. Each word in the book contains 3 letters. In the HTT gene, there is a run of the ‘word’ CAG. Doctors refer to this run of ‘words’ as the number of CAG repeats, that is, the number of times CAG is repeated in the gene.
Usually, there are 35 or fewer CAG repeats in the gene. If there are 36 or more, that is associated with HD. It is a bit complicated though because only some people with 36, 37, 38 or 39 CAG repeats develop HD and they may not start to show signs of it until later in life, even in their 70s or 80s. Most people with 40 or more CAG repeats show typical HD. The more CAG repeats in the gene, the earlier the age when symptoms first start.
When a person with more than 35 CAG repeats in one copy of their HTT gene has a child, and the child inherits that gene, the number of CAG repeats can increase (often referred to as an expansion of the gene), but it doesn’t always. An increase in the number of CAG repeats eg from 40 to 43 CAG repeats, means that the child will probably develop symptoms of HD at an earlier age than the parent did, assuming the parent was symptomatic. On average, down the generations of a family, the age of onset of HD will gradually become earlier. Geneticists call this ‘anticipation’.
Another aspect of the increase or expansion of CAG repeats is that on average, the number of CAG repeats is more likely to increase in the child of a man with HD than the child of a woman with HD. The reason for this is not known.
The HTT gene was first discovered in 1983 but it was not until 1993 that the gene fault (the CAG repeats) was identified. This discovery enabled use in medical practice as follows:
People could now have a test (usually a blood test) to confirm a clinical diagnosis of HD.
It also meant that adult children of a person with HD could take a test if they wished to see if they had inherited the faulty gene that causes HD or not. This is called ‘predictive’ or ‘pre-symptomatic’ testing. By international agreement, predictive testing is offered only to people aged 18 years or more because they need to give informed adult consent. The test is conducted as a series of appointments with specialists such as a social worker, clinical geneticist, psychiatrist and neurologist. It is a serious step to take, looking into the ‘crystal ball’ of one’s future, especially as there is currently no cure for HD. It is therefore very important that the person is as prepared for the result as they can be whether the result is positive (they carry the gene fault) or negative (they don’t carry it).
Finding the fault in the HTT gene also meant that a person carrying a faulty HD gene could choose to test during pregnancy to see if the baby had inherited the fault or not.
PREIMPLANTATION GENETIC TESTING (PGT)
It also meant that testing embryos created by in vitro fertilization (IVF) could be tested and an embryo predicted to carry a normal HTT gene could be transferred to the woman’s womb (uterus). The woman and her partner can then start the pregnancy knowing that the baby is very unlikely to have inherited HD.
HAVING A FAULTY HTT GENE VERSUS HAVING HD
It is important to distinguish between having a fault in the HTT gene and having HD. Having the fault in the gene does not necessarily mean the person has HD. For example, an adult who has taken a predictive test and has a ‘positive’ result (they carry the gene fault) does not have HD until they develop symptoms later.
This information is to be used as a guide and it is always recommended that you discuss any questions about your condition or treatment with your doctor or other health care professional.
If you have HD in your immediate family and would like more information about your options with regard to HD testing please do not hesitate to call one of the social workers of the South Australian Huntington's Disease Service (SAHDS) at the Repat Health Precinct on (08) 7117 5097 or (08) 7117 5096.