Huntington's Disease

Overview

Huntington's disease (HD) is a fatal hereditary disease that destroys neurons in areas of the brain involved in the emotions, intellect, and movement. The course of Huntington's is characterized by jerking uncontrollable movement of the limbs, trunk, and face (chorea); progressive loss of mental abilities; and the development of psychiatric problems.

Huntington's disease progresses without remission over 10 to 25 years and patients ultimately are unable to care for themselves. Huntington's disease usually appears in middle age (30-50 years), but can develop in younger and older people.

Juvenile HD (also called Westphal variant or akinetic-rigid HD) develops before the age of 20, progresses rapidly, and produces muscle rigidity in which the patient moves little, if at all (akinesia).

Autosomal Dominant Inheritance

In autosomal dominant inherited disease, a single abnormal allele is inherited from one parent. Alleles are the pairs of genes that determine individual characteristics.

Any child, male or female, with one affected parent has a 50% chance of inheriting Huntington's disease. The unaffected child of an affected parent cannot transmit the disease to their children because they have not inherited the abnormal gene.

Incidence and Prevalence

Experts estimate that one in every 10,000 persons-nearly 30,000 in the United States-have Huntington's disease. Juvenile Huntington's occurs in approximately 16% of all cases.

Huntington's disease is not prevalent within any particular population. All races and ethnic groups, and both sexes are affected.

Causes and Risk Factors

Having a parent with Huntington's is the risk factor. A child of an affected parent has a 50% chance of inheriting the disease.

The genetic mutation that occurs in gene IT-15, located on chromosome 4, alters the huntington protein, which is present in all human beings, and causes Huntington's disease. How the mutation of gene IT-15 alters the function of the protein is not well understood.

Signs and Symptoms

Huntington's disease produces three types of symptoms: movement, cognitive, and psychiatric. The sequence in which symptoms develop varies from person to person.

Movement

Uncontrolled movement, or tics, may develop in the fingers, feet, face, or trunk. This is the beginning stage of chorea-involuntary, rapid, ceaseless movement. Chorea can become more intense when the person is anxious or disturbed. Over time other symptoms, such as the following, emerge:

• Clumsiness
• Jaw clenching (bruxism)
• Loss of coordination and balance
• Slurred speech
• Swallowing and/or eating difficulty
• Uncontrolled continual muscular contractions (dystonia)
• Walking difficulty, stumbling, falling

Cognitive

Over time judgment, memory, and other cognitive functions begin to deteriorate into dementia. As Huntington's disease progresses, the ability to concentrate becomes more difficult. The person may have difficulty driving, keeping track of things, making decisions, answering questions, and may lose the ability to recognize familiar objects.

Psychiatric

Early psychiatric symptoms of Huntington's disease are subtle, varied, and easily overlooked or misinterpreted. Depression is the most common psychiatric symptom of Huntington's and often develops early in the course of the disease. Signs of depression include:

• Hostility/irritability
• Inability to take pleasure in life (anhedonia)
• Lack of energy

Some people develop manic-depression, or bipolar disorder, during the course of the disease.

A person with Huntington's also may exhibit psychotic behavior:

• Delusions
• Hallucinations
• Inappropriate behavior (e.g., unprovoked aggression)
• Paranoia

In late-onset disease (after age 50), the patient may suffer depression rather than experience sudden anger or irritability, and their memory, reasoning, and problem-solving skills may remain sharp.

Early signs of juvenile Huntington's disease often include subtle changes in handwriting and a rapid decline in school performance. The child may develop seemingly minor movement disorders, such as slowness, rigidity, tremor, or rapid muscle twitching. Other early signs of disease may include these changes:

• Behavioral changes
• Difficulty learning new things
• Speech difficulties

Children under the age of 15 may experience recurrent seizures and akinesia-muscle rigidity and stiffness. Children from 15 to 18 years of age tend to manifest the same symptoms of Huntington's disease as adults.

Complications

Lack of physical activity, dietary problems, and eating and swallowing problems can cause constipation, incontinence, and weight loss. Psychiatric and cognitive problems can lead to social isolation and deep depression.

Diagnosis

Diagnosis is based on a thorough personal and family medical history, physical examination (including a neurological exam), and a series of laboratory tests. The physician will ask about recent changes in intellectual or emotional function, which may be early signs of Huntington's disease.

Genetic Testing

Genetic testing involves taking a blood sample for DNA analysis to determine whether the distinct mutation for Huntington's disease has occurred in gene IT-15. A sample of DNA also may be required from a closely related affected relative, ideally a parent. This helps confirm the diagnosis of HD and is important if the family's history is in any way unclear, uncertain, or unusual. Persons who test positive and are considering pregnancy are advised to seek genetic counseling before they conceive.

Presymptomatic testing can be performed on adults, children, and even fetuses in the womb. Genetic testing of a fetus holds special challenges and risks, and some testing facilities choose not to do it.

At-risk couples wanting to have children may choose to undergo in vitro fertilization with preimplantation screening. In this procedure, embryos produced from the couple's sperm and eggs are screened to identify one that is free of the HD mutation, which is then implanted in the woman's uterus.

Testing Guidelineshuntingtons diseaseA positive test result can have profound, unanticipated impacts on patients and their families. Anyone contemplating genetic testing should obtain testing guidelines from the testing center or from an organization devoted to the interests of Huntington's disease patients and their families. Guidelines recommend that testing centers follow these practices:

• Counseling should be provided before and after the test, and before the results are known.
• Test results should be strictly confidential and should be disclosed only in person, and only to the individual being tested, regardless of the outcome.
• To protect the interests of minors, including confidentiality, testing should not be conducted for persons under 18 without a compelling medical reason, such as the appearance of HD symptoms in a child.

Computed Tomography (CT scan)

This painless diagnostic procedure produces computer-generated images of the brain's internal structures. Patients with HD often show shrinkage in two areas of the brain - the caudate nuclei and putamen - and enlargement of cavities within the brain called ventricles. The presence of these structural changes is not conclusive for Huntington's disease nor does their absence rule it out.

CT scans combined with other procedures such as magnetic resonance imaging (MRI scan) and/or positron emission tomography (PET scan) can be a helpful diagnostic tool, especially when evaluated in the context of family history and clinical symptoms.

Treatment

There is no cure for Huntington's disease. Treatment focuses on reducing symptoms, preventing complications, and providing support and assistance to the patient and those close to him or her.

Medication

Physicians often prescribe various medications to help control emotional and movement problems.

• Antipsychotics (hallucinations, delusions, violent outbursts): haloperidol, chlorpromazine, olanzapine (contraindicated if patient has dystonia)
• Antidepressants (depression, obsessive-compulsive behavior): fluoxetine, sertraline hydrochloride, nortriptyline
• Tranquilizers (anxiety, chorea): benzodiazepines, paroxetine, venlafaxin, beta-blockers
• Mood-stabilizers (mania, bipolar disorder): lithium, valproate, carbamazepine
• Botulinum toxin (dystonia, jaw clenching)

Because most drugs used to treat the symptoms of HD can produce undesirable side effects, ranging from fatigue to restlessness and hyperexcitability, physicians often prescribe the lowest possible dose.

Nutrition and Eating

Some Huntington's disease patients need a lot of time for meals because the loss of coordinated movement can make it difficult for them to swallow or feed themselves. These difficulties put them at risk for choking.

Food can be cut into small pieces, softened, or pureed to make swallowing easier. Swallowing therapy can help if started before there is serious difficulty. Dairy products should be avoided because they tend to increase the secretion of mucus, which can increase the risk for choking.

It is important for the patient to consume enough calories to maintain adequate body weight. The number of daily meals may have to be increased and vitamins and nutritional supplements may be recommended. If eating and dietary problems become severe, families and caregivers may need to consider the use of a feeding tube.

HD patients require large quantities of fluids, especially during hot weather, to avoid dehydration. Bendable straws can make drinking easier. In cases where the patient's muscular capability is severely weakened, water may have to be thickened with additives to the consistency of syrup before drinking is possible.

Complications such as constipation and incontinence can develop as a result of diet and lack of physical activity. A physician can provide dietary advice and information about how to cope with these problems.

Physical Activity

It is important for Huntington's disease patients to be as physically fit as their condition permits. Daily exercise promotes physical and mental well-being. Patients should walk as much as possible, even if assistance is necessary.

Because falls are always a risk, caregivers should keep the patient's surroundings free of hard, sharp objects. Wearing special padding during walks can help protect against injury from falls. Small weights worn around the ankles and sturdy, well-fitting shoes that slip on and off easily can help improve a patient's stability.

Social Activity

Unless and until the disease's progression prohibits it, people with HD should participate in outside activities, socialize, and pursue hobbies and interests. These activities also give family members and caregivers valuable time for themselves.

Support

Huntington's disease confronts patients and their caregivers with many complex problems that must be dealt with for years. While it may be emotionally difficult, it is important for patients and caregivers to make informed, carefully considered decisions regarding the future while the patient is capable of making his or her contribution to a planned course of action. Patients and their family members should discuss and consider issues such as legal concerns, home care, assisted care, and institutionalization.

Legal Affairs If possible, draw up wills and other important documents as early as possible to avoid legal problems later on, when the patient may be unable to represent his or her own interests. Legal assistance may be necessary if the patient encounters discrimination over insurance or employment.

Home Care Part-time help with housekeeping and physical care is often necessary. Federal, state, and local government programs and private agencies provide varying levels of domestic assistance, nutritional and nursing care, occupational therapy, and other home-based services.

Housing In some communities group housing facilities are available to persons who are alone and still independent, though not fully capable of providing for all routine needs, such as cooking and housekeeping. In these group residences, a resident attendant takes care of meals, housekeeping services, social activities, and local transportation needs.

Institutional Care The decision to institutionalize or place a family member in a congregate care facility can be enormously difficult. Professional counseling may be needed to help families deal with this important life choice.

Prognosis

Huntington's disease usually runs its full terminal course in 10 to 30 years. It has been observed that the earlier in life the symptoms of HD appear, the faster the disease progresses. The bedridden patient in the final stages of Huntington's disease often dies from complications such as heart failure or pneumonia.

Juvenile Huntington's disease runs it course comparatively fast, with death typically occurring in about 10 years.