Huntington disease is a progressive, neurodegenerative disease causing uncontrolled physical movements and mental deterioration. The disease was discovered by George Huntington of Pomeroy, Ohio, who first described a hereditary movement disorder.
Huntington disease is also called Huntington chorea, from the Greek word for "dance," referring to the involuntary movements that develop as the disease progresses. It is occasionally referred to as "Woody Guthrie disease" for the American folk singer who died from it. Huntington disease (HD) causes progressive loss of cells in areas of the brain responsible for some aspects of movement control and mental abilities. A person with HD gradually develops abnormal movements and changes in cognition (thinking), behavior, and personality.
The onset of symptoms of HD is usually between the ages of 30 and 50, although in 10% of cases, onset is in late childhood or early adolescence. Approximately 30,000 people in the United States are affected by HD, with another 150,000 at risk for developing this disorder. The frequency of HD is four to seven per 100,000 persons.
Huntington disease is caused by a change in the gene (an inherited unit which contains a code for a protein) of unknown function called huntingtin. The nucleotide codes (building blocks of genes arranged in a specific code that chemically form proteins), contain CAG repeats (40 or more of these repeat sequences). The extra building blocks in the huntingtin gene cause the protein that is made from it to contain an extra section as well. It is currently thought that this extra protein section, or portion, interacts with other proteins in brain cells where it occurs, and that this interaction ultimately leads to cell death.
The HD gene is a dominant gene, meaning that only one copy of it is needed to develop the disease. HD affects both males and females. The gene may be inherited from either parent, who will also be affected by the disease. A parent with the HD gene has a 50% chance of passing it on to each offspring. The chances of passing on the HD gene are not affected by the results of previous pregnancies.
Signs and symptoms
The symptoms of HD fall into three categories: motor or movement symptoms, personality and behavioral changes, and cognitive decline. The severity and rate of progression of each type of symptom can vary from person to person.
Early motor symptoms include restlessness, twitching and a desire to move about. Handwriting may become less controlled, and coordination may decline. Later symptoms include:
- Dystonia, or sustained abnormal postures, including facial grimaces, a twisted neck, or an arched back.
- Chorea, in which involuntary jerking, twisting, or writhing motions become pronounced.
- Slowness of voluntary movements, inability to regulate the speed or force of movements, inability to initiate movement, and slowed reactions.
- Difficulty speaking and swallowing due to involvement of the throat muscles.
- Localized or generalized weakness and impaired balance ability.
- Rigidity, especially in late-stage disease.
Cognitive changes include loss of ability to plan and execute routine tasks, slowed thought, and impaired or inappropriate judgment. Short-term memory loss usually occurs, although long-term memory is usually not affected. The person with late-stage HD usually retains knowledge of his environment and recognizes family members or other loved ones, despite severe cognitive decline.
Diagnosis of HD begins with a detailed medical history, and a thorough physical and neurological exam. Family medical history is very important. Magnetic resonance imaging (MRI) or computed tomography scan (CT scan) imaging may be performed to look for degeneration in the basal ganglia and cortex, the brain regions most affected in HD.
A genetic test is available for confirmation of the clinical diagnosis. In this test, a small blood sample is taken, and DNA from it is analyzed to determine the CAG repeat number. A person with a repeat number of 30 or below will not develop HD. A person with a repeat number between 35 and 40 may not develop the disease within their normal lifespan. A person with a very high number of repeats (70 or above) is likely to develop the juvenile-onset form. An important part of genetic testing is extensive genetic counseling.
Prenatal testing is available. A person at risk for HD (a child of an affected person) may obtain fetal testing without determining whether she herself carries the gene. This test, also called a linkage test, examines the pattern of DNA near the gene in both parent and fetus, but does not analyze for the triple nucleotide repeat (CAG). If the DNA patterns do not match, the fetus can be assumed not to have inherited the HD gene, even if present in the parent. A pattern match indicates the fetus probably has the same genetic makeup of the at-risk parent.
Treatment and management
There is no cure for HD, nor any treatment that can slow the rate of progression. Treatment is aimed at reducing the disability caused by the motor impairments, and treating behavioral and emotional symptoms.
Physical therapy is used to maintain strength and compensate for lost strength and balance. Stretching and range of motion exercises help minimize contracture, or muscle shortening, a result of weakness and disuse. The physical therapist also advises on the use of mobility aids such as walkers or wheelchairs.
Motor symptoms may be treated with drugs, although some studies suggest that anti-chorea treatment rarely improves function. Chorea (movements caused by abnormal muscle contractions) can be suppressed with
Occupational therapy is used to design compensatory strategies for lost abilities in the activities of daily living, such as eating, dressing, and grooming. The occupational therapist advises on modifications to the home that improve safety, accessibility, and comfort.
Difficulty swallowing may be lessened by preparation of softer foods, blending food in an electric blender, and taking care to eat slowly and carefully. Use of a straw for all liquids can help. The potential for choking on food is a concern, especially late in the disease progression. Caregivers should learn the use of the Heimlich maneuver. In addition, passage of food into the airways increases the risk for pneumonia. A gastric feeding tube may be needed, if swallowing becomes too difficult or dangerous.
Speech difficulties may be partially compensated by using picture boards or other augmentative communication devices. Loss of cognitive ability affects both speech production and understanding. A speech-language pathologist can work with the family to develop simplified and more directed communication strategies, including speaking slowly, using simple words, and repeating sentences exactly.
Early behavioral changes, including depression and anxiety, may respond to drug therapy. Maintaining a calm, familiar, and secure environment is useful as the disease progresses. Support groups for both patients and caregivers form an important part of treatment.
Experimental transplant of fetal brain tissue has been attempted in a few HD patients. Early results show some promise, but further trials are needed to establish the effectiveness of this treatment.
The person with Huntington disease may be able to maintain a job for several years after diagnosis, despite the increase in disability. Loss of cognitive functions and increase in motor and behavioral symptoms eventually prevent the person with HD from continuing employment. Ultimately, severe motor symptoms prevent mobility. Death usually occurs 15–20 years after disease onset. Progressive weakness of respiratory and swallowing muscles leads to increased risk of respiratory infection and choking, the most common causes of death. Future research in this area is currently focusing on nerve cell transplantation.
Watts, R. L., and W. C. Koller, eds. Movement Disorders. New York: McGraw-Hill, 1997.
Huntington Disease Society of America. 140 W. 22nd St. New York, NY 10011. (800) 345-HDSA.
Laith F. Gulli, MD