Huntington disease

Huntington disease is a progressive brain disorder that causes uncontrolled movements, mental and 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. As the disease progresses, involuntary jerking movements (chorea) become more pronounced. Affected individuals may have trouble walking, speaking, and swallowing. People with this disorder typically also experience changes in personality and a decline in thinking and reasoning abilities. Individuals with the adult-onset form of Huntington disease generally survive about 15 to 25 years after signs and symptoms begin.

A less common, early-onset form of Huntington disease begins in childhood or adolescence. Although both forms of the disorder involve movement problems and mental and emotional changes, some of the features of the early-onset form differ from those of the adult-onset form. In children, signs and symptoms can include slowness, clumsiness, frequent falling, rigidity, slurred speech, and drooling. School performance often declines as thinking and reasoning abilities become impaired. Seizures occur in 30 percent to 50 percent of individuals with this condition. The course of early-onset Huntington disease may be shorter than adult-onset Huntington disease; affected individuals generally survive 10 to 15 years after signs and symptoms appear.

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.

Mutations in the HD gene cause Huntington disease.

The HD gene provides instructions for making a protein called huntingtin. Although the function of this protein is unknown, it likely plays an important role in nerve cells. Huntington disease is caused by a mutation in which a DNA segment, known as a CAG repeat, is abnormally expanded within the HD gene. Normally, this segment is repeated 10 to 35 times within the gene. In people with Huntington disease, however, the CAG segment is repeated 36 to more than 120 times. The abnormally expanded CAG segment leads to the production of a huntingtin protein that contains a long stretch of the amino acid glutamine. (Amino acids are the building blocks of proteins.) The elongated protein disrupts the normal function of nerve cells in certain parts of the brain, and ultimately leads to the death of those cells. The dysfunction and loss of nerve cells cause the signs and symptoms of Huntington disease.

Read more about the HD gene.

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 HD gene is passed from one generation to the next, the size of the CAG repeat expansion often increases in size. Larger repeat expansions are usually associated with an earlier onset of signs and symptoms. This phenomenon is called anticipation.