Dear Doctor: My grandmother has a daughter and a son with Huntington's disease, and her husband and a few of her in-laws passed away from it. What can you tell us about this terrible disease? Who in the family could yet develop it?
Dear Reader: "Terrible" is the correct description of Huntington's disease. It's a rare genetic disease -- affecting about 5.7 out of 100,000 people in Europe, Australia and North America -- but it's unrelenting and eventually leads to death.
Almost everyone with Huntington's carries a disease-causing mutated gene on one chromosome and a normal copy on the other chromosome. That means their children have a 50/50 chance of having the mutated chromosome passed down to them. Unfortunately, in Huntington's, the mutated gene is dominant. So, even if a person has only one of the abnormal genes, he or she will develop the disease. So, to answer your question about the potential for other family members, any children of your grandmother's daughter and son with the disease have a 50/50 chance of developing it as well.
In the rare cases in which a person has two copies of the Huntington's gene, he or she will without doubt pass the disease on to all their children. Further, children who get the gene from their father are more likely to develop the disease earlier in life and to experience a more rapid deterioration.
Here's what happens: The mutant gene in Huntington's disease produces an abnormal protein that damages both the nucleus and other components of nerve cells, killing them. The nerve death is especially severe in the area of the brain called the striatum. These changes can be detected via MRI between nine and 20 years before a patient shows symptoms, which typically occur between the ages of 35 and 44.
The first sign of Huntington's disease is an involuntary movement abnormality termed chorea. Initially, this may be perceived as restlessness or lack of coordination. When it worsens, movements become random, jerky and uncontrollable, making it difficult for a person even to hold his or her posture or maintain a sustained motor action such as sticking out the tongue.
Psychiatric symptoms of depression and irritability, which can occur at any time during the disease, may be noticeable even before the onset of chorea. An estimated 33 to 76 percent of patients report anxiety, depression or apathy during the course of their illness. Three to 11 percent report symptoms of psychosis, including hallucinations, delusions and paranoia.
It gets worse. Patients' cognitive abilities are affected as well, leading to difficulty making decisions, multitasking or switching from one mental activity to another. Eventually, the memory problems lead to dementia.
In the latter stages of the disease, people may develop a rigid muscular state similar to Parkinson's. This can lead to the inability to walk. People can also experience weight loss, vision disturbances, and difficulty swallowing and breathing. The progression is prolonged, with death generally occurring 20 years after onset of symptoms.
Although genetic testing can easily diagnose the Huntington's mutation, the availability of such testing is relatively recent. Further, while it can guide decisions about whether or not to have children, it can do nothing to change the current reality. My heart goes out to your grandmother and the rest of your family.