Causes and Risk Factors of Huntington's Disease

Huntington’s disease is a rare condition, affecting approximately 1.22 out of every 100,000 people in the United States. The disease runs in families, and it is always caused by an inherited gene.

The genetic defect associated with Huntington’s disease causes degeneration of nerve cells in certain areas of the brain that control movement and thinking. Over time, gradually progressive deterioration of the brain leads to the characteristic symptoms of Huntington’s disease. 

Huntington's disease is caused by a gene mutation

Yuichiro Chino / Getty Images

Inheritance Pattern

Heredity is the only known cause of Huntington’s disease. It is inherited in an autosomal dominant pattern. If a person inherits the gene that causes Huntington’s disease, then the disease-producing gene “dominates” the other, normal non-disease-producing version of the gene, and the person will definitely develop the disease. 

Anyone who has the disease must have at least one copy of the disease-producing gene. If a person carries the gene that causes Huntington’s disease, each of their offspring has a 50% chance of inheriting the defective gene.

Since the usual age disease onset is between 30 to 50, many people who have the disease would not have developed symptoms by the time they have children.

In a family in which one parent has the gene, about half of the siblings would be expected to inherit the gene that causes Huntington’s disease, and would therefore develop the disease.

Offspring of a person who has Huntington’s disease also have a 50% chance of not inheriting the gene—and would thus not develop the disease or pass the disease down to their own children.

 

Genetics 

The HTT gene is the gene that causes Huntington’s disease, and it is located on chromosome four. Every person inherits two copies of chromosome four, one from their biological father and one from their biological mother. 

The genetic defect that causes Huntington’s disease is described as a CAG repeat in the HTT gene. This is a mutation (alteration from the normal sequence) in the deoxyribonucleic acid (DNA) molecule.

The mutation consists of a repeated pattern of cytosine, adenine, and guanine, which are nucleotides in the DNA molecule that code for the production of the body's traits.

With Huntington’s disease, the CAG repeat might occur between 10 to 30 times, and the extra nucleotides alter the instructions of the HTT gene—which normally codes for huntingtin protein. A person who has Huntington’s disease will not necessarily have the same exact number of CAG repeats as the parent who they inherited the disease from.

Juvenile Huntington's Disease

There is also a juvenile form of Huntington’s disease that begins during childhood or young adulthood and advances more quickly than the adult form of the disease, producing more severe and more rapidly progressive effects at a younger age.

The juvenile form, which follows the same hereditary autosomal dominant pattern as the adult form, is associated with a higher number of CAG repeats than the adult form. People who have juvenile Huntington’s disease have an average of approximately 60 CAG repeats in the HTT gene.

Repair Proteins  

In addition to the CAG repeat mutation of the HTT gene, people with Huntington’s disease also have gene defects in genes that code for proteins that help repair DNA.

These proteins help maintain the normal structure of DNA and might help prevent CAG repeat mutations. There is evidence that having more defects in these repair genes could also lead to more CAG repeats and an earlier onset of the condition.

Brain Changes

Studies show that people with Huntington’s disease have abnormalities of the caudate and putamen areas of the brain that are normally associated with thinking, memory, behavior, and motor control. Altered function of the neurotransmitters, especially dopamine, in these areas may play a role in Huntington's disease.

These changes include atrophy (shrinking), as well as deposits of material, such as cholesteryl esters (CE), a type of fat molecule.

Huntington’s disease is associated with inflammatory destruction of brain cells that had previously been functional and healthy. The defective huntingtin protein is believed to play a role in developing the disease. The function of this protein is not known for certain, but it may be involved in protecting brain cells from toxins.

In Huntington’s disease, a process described as autophagy occurs when cells are destroyed and then degenerate. It is proposed that the disease may occur due to damage induced by toxins along with inadequate protection of brain cells. The genetic defect may either promote toxin production or result in inadequate protection from toxins.

Lifestyle Risk Factors 

Huntington’s disease tends to occur during middle age, and the juvenile form develops after normal neurological development has begun.

Unlike some hereditary conditions, there isn't an issue with formation of the brain in Huntington’s disease—instead, there is a problem with maintaining health of the brain cells after they have already formed adequately. 

There are some populations that have a slightly higher incidence of Huntington’s disease, but there are no lifestyle factors or habits that have been shown to either cause the condition or help prevent it.

Huntington's disease occurs throughout the world, with a slightly lower prevalence in Asian countries than in Europe, the U.S., and Australia. The condition is also slightly more common in women than men, and slightly more common among people of a lower socioeconomic level.

Experts aren’t certain about the reason for these trends, and currently the understanding is that some populations are more likely to carry the causative mutation.

Other explanations for varying incidence among different populations include:

  • Researchers suggest that genetic testing and identification of the disease could differ among different populations and that this could be a reason for the variation in diagnosis, rather than an actual difference in its occurrence.
  • Investigators suggest that women might be more predisposed to a higher number of CAG repeats than men.
  • Research shows that having cognitive and motor deficits could lead to lower income levels for those affected by the condition and their offspring.

A Word From Verywell

Huntington’s disease is caused by a hereditary genetic defect in chromosome four. The physiological process by which the genetic defect causes the effects of the disease is complex, involving progressive damage to certain areas of the brain.

While nothing can be done to prevent Huntington’s disease from developing or to reverse the neurological degeneration if you have inherited the causative gene, an understanding of the biological cause may eventually lead to discoveries that could help prevent disease progression in people who have the gene mutation.

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