What Is Huntington Disease?

Huntington disease is a progressive brain disorder that causes uncontrolled movements, emotional problems, and loss of cognitive ability.

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.

George Huntington

Front page of George Huntington’s communication, “On Chorea”.
On the right is an 1872 photo of George Huntington (1850–1916), American physician

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.

Juvenile Huntington Disease

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.

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.

Huntington Genetic Changes

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 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.

Inheritance

Autosomal dominant inheritance

Credit: Français Domaina, CC BY-SA 3.0

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).

Symptoms Of Huntington Disease

Behavior changes may occur before movement problems, and can include:

  • Behavioral disturbances
  • Hallucinations
  • Irritability
  • Moodiness
  • Restlessness or fidgeting
  • Paranoia
  • Psychosis

Abnormal and unusual movements include:

  • Facial movements, including grimaces
  • Head turning to shift eye position
  • Quick, sudden, sometimes wild jerking movements of the arms, legs, face, and other body parts
  • Slow, uncontrolled movements
  • Unsteady gait, including “prancing” and wide walk
  • Dementia that slowly gets worse, including: Disorientation or confusion, Loss of judgment, Loss of memory, Personality changes, Speech changes, such as pauses while talking

Additional symptoms that may be associated with this disease:

  • Anxiety, stress, and tension
  • Difficulty swallowing
  • Speech impairment

Treatment

There is no cure for HD. There is no known way to stop the disease from getting worse.

The goal of treatment is to slow the symptoms and help the person function for as long as possible. Medicines can be prescribed, depending on the symptoms.

Dopamine blockers may help reduce abnormal behaviors and movements. Drugs such as amantadine and tetrabenazine are used to try to control extra movements.

Depression and suicide are common among persons with HD. It is important for caregivers to monitor for symptoms and seek medical help for the person right away. As the disease progresses, the person will need assistance and supervision, and may eventually need 24-hour care.

Sandy Sulaiman
Learning to Live with Huntington’s Disease: One Family’s Story
Jessica Kingsley Publishers; (2007)
ISBN-13: 978-1843104872

Bates GP
History of genetic disease: the molecular genetics of Huntington disease – a history
Nat Rev Genet. 2005 Oct;6(10):766-73

Gonzalez-Alegre P, Afifi AK
Clinical characteristics of childhood-onset (juvenile) Huntington disease: report of 12 patients and review of the literature
J Child Neurol. 2006 Mar;21(3):223-9

Imarisio S, Carmichael J, Korolchuk V, Chen CW, Saiki S, Rose C, Krishna G, Davies JE, Ttofi E, Underwood BR, Rubinsztein DC
Huntington’s disease: from pathology and genetics to potential therapies
Biochem J. 2008 Jun 1;412(2):191-209. doi: 10.1042/BJ20071619