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Please remember that this information is a brief overview and is for educational purposes only. It is not intended to be a substitute for professional medical advice. Always consult your health care provider with any questions you may have regarding your specific medical condition.
What is Huntington's Disease (HD)?
Huntington disease is a progressive brain disorder that causes uncontrolled movements, emotional problems, and loss of thinking ability (cognition). Adult-onset Huntington disease, the most common form of this disorder, usually appears in a person's thirties or forties. Early signs and symptoms can include irritability, depression, small involuntary movements, poor coordination, and trouble learning new information or making decisions. Many people with Huntington disease develop involuntary jerking or twitching movements known as chorea. As the disease progresses, these movements become more pronounced. Affected individuals may have trouble walking, speaking, and swallowing. People with this disorder also experience changes in personality and a decline in thinking and reasoning abilities. Individuals with the adult-onset form of Huntington disease usually live about 15 to 20 years after signs and symptoms begin.
A less common form of Huntington disease known as the juvenile form begins in childhood or adolescence. It also involves movement problems and mental and emotional changes. Additional signs of the juvenile form include slow movements, clumsiness, frequent falling, rigidity, slurred speech, and drooling. School performance declines as thinking and reasoning abilities become impaired. Seizures occur in 30 percent to 50 percent of children with this condition. Juvenile Huntington disease tends to progress more quickly than the adult-onset form; affected individuals usually live 10 to 15 years after signs and symptoms appear.
The Genetic Cause of HD
HD is caused by mutation in a gene located on chromosome 4. This gene is found in every human being, and contains a CAG repeat sequence. We have not yet discovered the gene's normal function. In a case of HD, the gene contains an abnormally large number of CAG repeats. The larger the number of triplet repeats, generally speaking, the earlier in life one will develop HD. Furthermore, when the gene is passed from father to child (but not when passed from mother to child) the gene may lengthen even more, resulting in an earlier age of onset for the disease. This phenomenon is known as anticipation.
Genes for diseases can be either dominant or recessive. The gene for HD is dominant. Each child of an affected parent has a 50/50 chance of getting the mutant gene, and therefore has a 50% chance of inheriting the disease. On the other hand, if people with a parent suffering from HD do not inherit the mutant gene, they cannot pass it on to anyone else.
What genes are related to Huntington disease?
Mutations in the HTT gene cause Huntington disease. The HTT gene provides instructions for making a protein called huntingtin. Although the function of this protein is unknown, it appears to play an important role in nerve cells (neurons) in the brain.
The HTT mutation that causes Huntington disease involves a DNA segment known as a CAG trinucleotide repeat. This segment is made up of a series of three DNA building blocks (cytosine, adenine, and guanine) that appear multiple times in a row. Normally, the CAG segment is repeated 10 to 35 times within the gene. In people with Huntington disease, the CAG segment is repeated 36 to more than 120 times. People with 36 to 39 CAG repeats may or may not develop the signs and symptoms of Huntington disease, while people with 40 or more repeats almost always develop the disorder.
An increase in the size of the CAG segment leads to the production of an abnormally long version of the huntingtin protein. The elongated protein is cut into smaller, toxic fragments that bind together and accumulate in neurons, disrupting the normal functions of these cells. The dysfunction and eventual death of neurons in certain areas of the brain underlie the signs and symptoms of Huntington disease.
How common is Huntington disease?
Huntington disease affects an estimated 3 to 7 per 100,000 people of European ancestry. The disorder appears to be less common in some other populations, including people of Japanese, Chinese, and African descent.
How do people inherit Huntington disease?
This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. An affected person usually inherits the altered gene from one affected parent. In rare cases, an individual with Huntington disease does not have a parent with the disorder.
As the altered HTT gene is passed from one generation to the next, the size of the CAG trinucleotide repeat often increases in size. A larger number of repeats is usually associated with an earlier onset of signs and symptoms. This phenomenon is called anticipation. People with the adult-onset form of Huntington disease typically have 40 to 50 CAG repeats in the HTT gene, while people with the juvenile form of the disorder tend to have more than 60 CAG repeats.
Individuals who have 27 to 35 CAG repeats in the HTT gene do not develop Huntington disease, but they are at risk of having children who will develop the disorder. As the gene is passed from parent to child, the size of the CAG trinucleotide repeat may lengthen into the range associated with Huntington disease (36 repeats or more).
Important Information About HD Testing
It is important to understand that while people are born with the mutated gene for HD, in most cases they will not develop the symptoms until later in life. Therefore someone can be without symptoms or presymptomatic for a number of years. In the past, there was no way to test for the abnormal gene, but now a blood test can determine whether or not an individual carries the gene for HD. This test can be used in cases of suspected HD, to confirm the diagnosis, or it can be used as a predictive test in individuals who are at risk for HD. People who are at risk may want to undergo predictive testing in order to put their minds at ease, to plan for their medical needs, or prior to having children. The decision to have such a test is a momentous one and should not be taken lightly. Most centers that do predictive testing, require a period of counseling before and after the test.
What Are the Characteristics of HD?
Onset is usually in mid-life, but can occur any time from childhood to old age. The initial signs of this disorder may be subtle. HD is characterized by a movement disorder, dementia, and psychiatric disturbances. Additional characteristics of HD include personality changes, weight loss (probably from a combination of difficulty eating, and calories burned by the involuntary movements), difficulty swallowing, and hard-to-understand speech.
The Course of HD
Once an individual develops signs of HD the course of the disease can last anywhere from ten to thirty years. Typically, the course of HD can be roughly divided into three stages.
Early Stage:In this stage patients can still perform most of their usual activities. They may still be working and may still be able to drive. Involuntary movements are mild and infrequent, speech is still clear, and dementia, if present at all, is mild.
Middle Stage:At this stage patients are more disabled and may need assistance with some of their activities of daily living. Falls, weight loss, and swallowing difficulties may become a problem. Dementia is more obvious to the casual observer. Involuntary movements are more pronounced.
Late Stage:Patients entering this stage of the disease require almost total care and may reside in hospitals or nursing homes, although some remain at home. They may no longer be able to walk or speak. They may be more rigid now and show fewer involuntary movements. Individuals in this stage may or may not be able to swallow food. At this stage most patients do not seem to suffer much as they are apparently unaware of their surroundings. When the patient passes away, the cause of death is usually related to malnutrition, pneumonia, or heart failure.
What Treatments Are Available?
At this time, there is no cure for HD. Researchers are working on a number of treatments that may slow down the progression of the disease. There are a number of interventions available today that improve the quality of life for HD sufferers. In the early and middle stages of the disease, medications can be given in small doses to HD patients to help suppress the involuntary movements. Depression and other psychiatric conditions in people with HD can be quite effectively treated. Proper nutrition, exercise and precautions in the home can help minimize many of the potential consequences of HD such as weight loss, falls, and choking on food. Finally contact with other HD sufferers, family members, and care-providers can be a vital source of support for HD patients and their families.
People with HD should discuss their concerns and wishes about treatments/interventions (e.g. feeding tubes, resuscitation requests) and autopsies with their families and doctors while they are still able to speak for themselves.