Huntington’s disease is a neurodegenerative disorder characterized by uncontrolled jerking and writhing movements known as chorea, loss of thinking ability, and psychiatric problems. It was first documented in 1872 by a 22-year-old American doctor named George Huntington.

Genetics of Huntington’s disease

Huntington’s is caused by a mutation of the huntingtin (HTT) gene. The mutation is called a CAG trinucleotide repeat expansion because the segment of the gene containing the CAG portion of DNA repeats is longer than usual. The longer this repeat region is, the earlier the symptoms of the disease appear. They also tend to be more severe.

Huntington’s is inherited in an autosomal dominant manner, meaning that a person only needs one copy of the defective gene to develop the disease. People have two copies of genes, one from their father and one from their mother.

What happens in Huntington’s disease?

Huntington’s affects two brain areas — the basal ganglia, which are responsible for movement coordination, and the cortex, which controls thought, behavior, and memory.

A mutated HTT gene leads to degeneration in these parts of the brain. The result is symptoms such as trouble controlling movement, walking difficulties, and problems with speech and swallowing. People with Huntington’s may experience cognitive dysfunction, including thinking, planning, and organizing problems. Emotional instability and behavioral changes are also common in a person with Huntington’s.

Symptoms of the disease vary and are progressive, meaning they get worse over time.

Types of Huntington’s disease

Huntington’s symptoms typically appear in a person’s 30s and 40s. This is called adult-onset Huntington’s disease, and is the most common type.

Sometimes the symptoms appear in childhood or adolescence. Juvenile-onset Huntington’s tends to progress more quickly than the adult form. This is because those with a juvenile form have a longer CAG repeat expansion in their HTT gene. Those with juvenile Huntington’s frequently experience muscle stiffness and seizures instead of chorea.

Diagnosing Huntington’s disease

Genetic testing for a mutation of the HTT gene can help doctors determine whether a person will develop the disease. Because Huntington’s progresses slowly, it is possible to test positive for the disease without experiencing symptoms. In these situations, there is a 50 percent chance of a person passing on the disease-causing gene to their children. Genetic counseling can help families with Huntington’s gene mutations make informed reproductive choices.

When people have Huntington’s symptoms, doctors use magnetic resonance imaging or computerized tomography scans to look for changes in their brain.

Managing Huntington’s disease

There is no cure for Huntington’s, but many treatments can help patients manage their symptoms and improve their quality of life. Examples of treatments include the recently approved Deutetrabenazine (austedo) for chorea, anticonvulsant drugs for seizures, and antidepressants for mood changes.

In addition, scientists are developing a number of experimental therapies for Huntington’s, such as VX15/2503 and AMT-130.

Physical therapy can help patients regain some control over their movements.

