Chorea (disease)

Definition

Huntington's disease is an inherited, progressive, neurodegenerative disease causing uncontrolled physical movements and mental deterioration.

Description

Huntington's disease (HD) is a genetic disorder that 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, 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 it.

Huntington's disease is also called Huntington's 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's disease" for the American folk singer who died from it.

Causes & symptoms

Causes

Huntington's disease is caused by a defect in the gene for a protein of unknown function called huntingtin. The defective gene contains 40 or more so-called "CAG repeats," compared to only 30 of these repeats in the normal huntingtin gene. C, A, and G are DNA nucleotides, the building blocks of genes. 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 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.

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 muscles of the throat.
• Localized or generalized weakness, and impaired balance ability.
• Rigidity, especially in late-stage disease.

Personality and behavioral changes include depression, irritability, anxiety, and apathy. The person with HD may become impulsive, aggressive, or socially withdrawn.

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 spared. 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

Diagnosis of HD begins with a detailed medical history, and a thorough physical and neurological exam. Family medical history is very important, since HD is an inherited disease. 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.

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 "nondisclosing" 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 repeat itself. 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. It does not indicate whether the parent (or fetus) actually has the defective gene.

Treatment

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 can be suppressed with drugs that deplete dopamine, an important brain chemical regulating movement. As HD progresses, natural dopamine levels fall, leading to loss of chorea and an increase in rigidity and movement slowness. Treatment with L-dopa (which resupplies dopamine) may help here. Frequent reassessment of the effectiveness and appropriateness of any drug therapy is necessary.

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 for through use of 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. Information on local support groups is available from the Huntington's Disease Society of America.

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.

Prognosis

The person with Huntington's 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 respiratory infection, and choking, the most common causes of death.

Prevention

Huntington's disease cannot be prevented in a person with the gene defect.

Key Terms

Cognition

The mental activities associated with thinking, learning, and memory.

Computed tomography (CT) scan

A process which uses x rays taken from many different angles to view a cross-section of the body's tissues.

DNA

Deoxyribonucleic acid; the genetic material that controls heredity.

Heimlich maneuver

An action designed to expel an obstructing piece of food from the throat. It is performed by placing the fist on the abdomen, underneath the breastbone, grasping the fist with the other hand (from behind), and thrusting it inward and upward.

Neurodegenerative

Relating to degeneration of nerve tissues.

Further Reading

For Your Information

Books

• Watts R.L., and W.C. Koller, eds. Movement Disorders. New York: McGraw-Hill, 1997

  Organizations

• Huntington's Disease Society of America. 140 W. 22nd St. New York, NY 10011. (800) 345-HDSA.

Gale Encyclopedia of Medicine. Gale Research, 1999.