Genetic: Huntington Disease

Definition
Description
Demographics
Causes and Symptoms
Diagnosis
Treatment
Prognosis
Prevention
The Future
For more information

Definition

Huntington disease, or HD, is a rare and incurable genetic disorder caused by a defective gene on chromosome 4.

Description

HD is a rare but invariably fatal disease caused by an abnormal stretch of DNA in a single gene on chromosome 4. It has been known for centuries; in the Middle Ages it was grouped together with other movement disorders under the name of St. Vitus’ dance. Huntington disease got its present name from Dr. George Huntington (1850–1916), an American doctor who published the first medical description of the disease in 1872, one year after completing medical school. Dr. Huntington was the first writer to prove that the disease is inherited; his grandfather and father had both practiced medicine on Long Island and had kept records of a single family with four generations of members with HD.

It was not until 1983, however, that geneticists were able to find out which of the twenty-three pairs of human chromosomes carries the gene that causes HD. In that year it was discovered that the gene was located somewhere on chromosome 4, although the gene itself was not pinpointed until 1993. In the meantime researchers were studying families living in poor fishing villages along the shores of Lake Maracaibo in Venezuela. This group of families has the highest rate of HD in the world—700 per 100,000 people. Tissue samples from these families helped to locate the gene that causes HD.

Demographics

Huntington disease is uncommon, affecting between four and eight people per 100,000 in the United States and between two and ten per 100,000 in Europe. There are a few countries other than Venezuela with higher than average rates of HD, including Mauritius (forty-six per 100,000 people) and Tasmania (eighteen per 100,000 people). The disease appears to be somewhat more common among people of European ancestry than among Africans or Asians.

Men and women are equally likely to inherit the defective gene, develop the disease, and pass it on to their children. Huntington disease is one of only a few genetic disorders occurring as a dominant trait, that is, to develop the disease a person only requires one abnormal gene (whereas with recessive traits, to cause overt disease, one must have abnormal genes on both pairs of the chromosome). In many cases the first symptoms appear when patients are in their late 30s or early 40s; however, 10 percent of all cases appear in people younger than twenty. This form of the disease is called juvenile HD. The disease has been known to appear in children as young as two years and in adults over eighty years of age. Most patients die between ten and twenty-five years after the first symptoms appear.

Causes and Symptoms

Huntington disease is caused by a defective gene on chromosome 4 that produces an abnormal protein. This protein causes the death of nerve cells in various parts of the brain that control movement, cognition (thinking), and behavior. The defect in the gene is a DNA repeat that occurs from thirty-six to 120 times, whereas there are only seven to thirty-five repeats in a normal gene. The larger the number of repeats, the earlier the symptoms of HD are likely to appear; people with more than sixty repeats are likely to develop juvenile HD. Moreover, the number of repeats increases in each successive generation of people with the defective gene; this characteristic of the disease is known as anticipation.

People can inherit the faulty gene from either parent; however, inheriting it from the father appears to speed up the onset of the disease. Most people who develop juvenile HD inherited the defective gene from the father, whereas people who first develop symptoms after age thirty-five are more likely to have inherited the defective gene from their mother.

The symptoms of Huntington disease include physical, mental, and emotional symptoms. In most cases the physical indications of the disease are the first to appear, although some patients have memory problems or emotional disturbances as the earliest symptoms.

The House of Love and Faith

The House of Love and Faith, or Casa Hogar Amor y Fe in Spanish, is a clinic in Venezuela run by Dr. Margot de Young for the families near Lake Maracaibo affected by Huntington disease. There are 14,000 descendants of the first known family member who developed the disease in the 1800s living in this area. Many are at risk of developing HD themselves. The fishing villages around the lake have been impoverished by the disease; children often quit school at age seven or eight in order to care for older relatives dying of HD. By the time they are teenagers, many have had children, thus passing on the gene for the disease to the next generation. Because many families in the villages have ten to twelve children, it is not unusual for such families to have five or more children with juvenile HD.

Dr. de Young's clinic, located in a building that was once a bar, has thirty-four beds for patients in the last stages of Huntington disease. The doctor also provides food, medicines, and basic information about health care and nutrition to the patients' family members. The clinic selectively hires its health care workers from among the HD families; they are proud of their work in the small clinic and do their best to keep it a clean and welcoming place.

• Physical symptoms: uncontrollable fidgeting or sudden jerky movements (chorea); loss of coordination and balance; difficulty changing the direction of the eyes without moving the entire head; uncontrollable facial grimaces; difficulties with speech and swallowing.
• Cognitive symptoms: dementia (loss of memory and ability to make plans or solve problems); disorientation and confusion.

• Emotional changes: depression; personality changes; antisocial behavior; hallucinations; psychosis (complete loss of contact with reality).

Younger patients with juvenile HD may have symptoms resembling those of Parkinson's disease, such as rigid muscles, slow movement, drooling, and frequent falls. Between 30 and 50 percent of these patients also develop seizures.

As the disease progresses, patients gradually lose their ability to walk or stand and may be confined to a wheelchair or completely bedridden. They may become completely stiff or unable to eat; most patients eventually have to be institutionalized.

Diagnosis

The doctor may order various imaging studies of the brain, such as a computed tomography (CT) scan or magnetic resonance imaging (MRI). Patients with HD will typically show some loss of brain tissue in a specific area of the brain called the caudate nucleus. This part of the brain primarily controls movement but is also involved in learning and memory. It is one of the first parts of the brain to be damaged by the disease.

Genetic testing can be done to confirm the diagnosis of Huntington disease. It involves a blood sample that counts the number of DNA repetitions in the HD gene. People who are at risk for HD can request the test before they develop symptoms. They must undergo several counseling sessions before the test, however, to make sure that they can cope with the results because there is no way to cure HD or slow its appearance.

Treatment

Treatments for Huntington disease are primarily intended to help patients manage their symptoms, since there is no cure for the disease. Most patients are given several medications, which may include antiseizure drugs, antidepressants, tranquilizers, drugs to control hallucinations and other symptoms of psychosis, and drugs to control involuntary body movements.

Other treatments include physical therapy to help keep the patient's muscles strong and flexible, speech therapy to help with difficulties in

talking clearly, and occupational therapy to help the patient take care of dressing, bathing, and other basic needs as long as possible.

Prognosis

There is no cure for HD. Patients die about nineteen years on average after the first symptoms appear, most commonly of pneumonia or another infection, malnutrition from inability to eat, or suicide.

Prevention

One reason why Huntington disease has not died out among humans is that the earliest symptoms often do not appear until after the affected person has had children and thus conveyed the defective gene into the next generation. People with a parent who has the defective gene should receive genetic counseling before starting a family. Some younger people choose to be tested for the gene before marrying in order to tell whether they will develop HD themselves as well as risk passing on the defective gene to children. People at risk for HD can consider adoption if they wish to start a family, or they can use a form of assisted reproduction in which embryos are screened for the Huntington gene mutation before being implanted in the woman's uterus.

The Future

It is not likely that HD will ever be completely wiped out even if everyone who presently might have the defective gene agreed to be tested and further agreed not to have children if they turned out to have the gene. The reason why HD would reappear at some point is that some people can develop the disease even without a family history of HD because of a spontaneous mutation (change in their genetic material).

Researchers are looking in several different directions for a possible cure for Huntington disease. One possibility is gene silencing, a technique that would involve using a short sequence of DNA to block the expression of the DNA repeats on the Huntington gene. Another possibility is a combination of certain drugs used to treat cancer with other drugs used to treat AIDS. This type of drug therapy has not yet been tested in humans, however. Still a third possibility is implanting stem cells in the damaged parts of the brain to replace the nerve cells that have already been destroyed.

SEE ALSO Parkinson disease

WORDS TO KNOW

Anticipation: A condition in which the symptoms of a genetic disorder appear earlier and earlier in each successive generation.

Chorea: A general term for movement disorders marked by loss of coordination and involuntary motions of the head and limbs.

Dementia: Loss of memory and other mental functions related to thinking or problem-solving.

Mutation: A change in the genetic material of an organism.

Psychosis: A severe form of mental illness involving loss of contact with reality.

Stem cell: An unspecialized human cell that has the capacity to form itself into a nerve cell or other type of specialized cell.

For more information

BOOKS

Huntington's Disease Society of America (HDSA). Huntington's Disease. New York: HDSA, 2007. Available online in PDF format at http://www.hdsa.org/images/content/1/1/11287.pdf (accessed November 4, 2008).

Knowles, Johanna. Huntington's Disease. New York: Rosen Publishing Group, 2007.

Quarrell, Oliver. Huntington's Disease. New York: Oxford University Press, 2008.

PERIODICALS

Goldberg, Carey. “Huntington's Gene Has Led to Clues, But Not Yet Cures.” Boston Globe, October 23, 2006. Available online at http://www.boston.com/news/globe/health_science/articles/2006/10/23/huntingtons_gene_has_led_to_clues_but_not_yet_cures/?page=full (accessed April 23, 2008).

Harmon, Amy. “Facing Life with a Lethal Gene.” New York Times, March 18, 2007. Available online at http://query.nytimes.com/gst/fullpage.html?res=9501E4DD1630F93BA25750C0A9619C8B63&sec=&spon=&page-wanted=all# (accessed April 23, 2008). Article about a young woman who chose to be tested for the Huntington's gene and is coping with the test results. A video about the article is available on the newspaper's website at http://www.video.on.nytimes.com/index.jsp?fr_story=d962010d883be3d1278974769d1226cf0ed34933 (accessed April 23, 2008). The video shows some patients with HD and is about 3 minutes in length.

Hoag, Christina. “A Tale of Pain and Hope on Lake Maracaibo.” Business Week, May 29, 2000. Available online at http://www.businessweek.com/2000/00_22/c3683206.htm (accessed April 23, 2008). This is an article about the village in Venezuela with the highest rate of HD in the world.

WEB SITES

Conomy, John P. “Dr. George Huntington and the Disease Bearing His Name.” Huntington's Disease Society of America, Northeast Ohio Chapter. Available online at http://www.lkwdpl.org/hdsa/conomy.htm (accessed April 23, 2008). This is a short biography of the doctor who first described HD.

Genetics Home Reference. Huntington Disease. Available online at http://www.ghr.nlm.nih.gov/condition=huntingtondisease (updated July 2006; accessed April 23, 2008).

Mayo Clinic. Huntington's Disease. Available online at http://www.mayoclinic.com/health/huntingtons-disease/DS00401 (updated May 9, 2007; accessed April 23, 2008).

Understanding Evolution. Huntington's Chorea: Evolution and Genetic Disease. Available online at http://www.evolution.berkeley.edu/evolibrary/article/0_0_0/medicine_05 (accessed April 23, 2008).