Huntington's Disease

Huntington’s disease (HD) is not very common.  Worldwide, there are about 2.7 cases per 100,000 people.  It most commonly comes on in midlife.  For those whom it effects, the disease can be devastating. 

What are the Signs of Huntington's Disease?

Signs and symptoms include writhing, dancelike movements called chorea.  The movements cannot be controlled. Initially, the movements can be small, and may be mistaken for fidgeting.

  Patients may or may not be aware of the movements. Ultimately, the abnormal movements impact breathing and swallowing as well.

Mood changes are also common, and sometimes are the first symptoms in Huntington’s disease.  Depression, anxiety or irritability are very common.  Compulsive behavior can also occur.  Between 3 to 11 percent of patients have psychosis, with paranoia, delusions, or hallucinations. As many as 1/5 of people with Huntington’s consider suicide, and the suicide rate is as high as 7 percent.

Cognition declines in Huntington’s disease—dementia is the natural endpoint of the disease.  Unlike Alzheimer’s disease, which predominantly impacts memory, people with HD lose executive function—they struggle to make decisions or multitask, for example.  While people with HD may have memory problems, they will improve if given cues, in contrast to Alzheimer’s disease.

In addition, people with Huntington's disease frequently lose weight.

  The reason for this is unclear. Increased energy expenditure due to chorea may be a factor. Ultimately, people lose motivation and capability to move, and are bedridden.  Complications resulting from lack of movement lead to death generally 10 to 30 years after the first appearance of symptoms.

What Causes Huntington's disease?

Huntington’s disease is caused by a CAG trinucleotide repeat expansion in the huntingtin gene on chromosome 4p.  This means that the genetic code "cytosine-adenosine-guanine" repeats itself more on that chromosome than in healthy controls.  The disease is inherited in an autosomal dominant fashion, meaning that if a parent has the disorder, it’s likely that children will as well. While a family history of HD is a very important risk factor, about 8% of cases have no known family history of HD, suggestive of either new mutations or misdiagnoses of family members.

Furthermore, the repeat tends to expand with each generation, leading to more serious symptoms starting at an earlier age, a process called anticipation.  Repeat sizes greater than 38 are always expressed.  Repeats of size 33 to 38 may or may not cause the disease.  Alleles with 40 to 50 CAG repeats are common in patients with the adult form, whereas juvenile Huntington’s is associated with 60 to as high as 100 or more.  Environmental and other genes may also play a role in the time and severity of disease onset.

The CAG repeat results in creation of a mutant huntingtin protein. Exactly how this leads to the signs and symptoms of Huntington’s disease remains a mystery.  Huntington is present in a variety of tissues throughout the body, But the pathology of Huntington’s disease only seems to impact the brain.  It’s likely that the abnormal protein actively contributes to symptoms, rather than the disease resulting from a loss of normal huntingtin.  Huntingtin is thought to be critical for early embryonic development, as mice in whom the gene is inactivated die in gestation. 

In HD, large aggregates build up in the cytoplasm and nuclei of cells, which can be seen by electron microscopy.  Huntingtin collects in aggregates in the brain, though the role of those aggregates in the disease is controversial—it may actually be a protective measure against less evident disease processes. 

Ultimately, nerve cells are lost from the caudate and putamen in the center of the brain. These regions are important not only for movement, but for important aspects of thinking and emotion as well.

What Can Be Done? 

At this time there's no cure for Huntington's disease, but symptomatic treatments can help.  


Ropper AH, Samuels MA. Adams and Victor's Principles of Neurology, 9th ed: The McGraw-Hill Companies, Inc., 2009 

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