Huntington’s Disease

Huntington’s disease (HD) results from the degeneration of neurons of structures deep within the brain, the basal ganglia, which are responsible for movement and coordination. It is a progressive, neurodegenerative disorder typically characterized by involuntary movements (chorea), behavioral and personality changes, and cognitive decline (dementia). It is caused by a dominantly inherited gene mutation that can be passed down from generation to generation, yet there is great variability in HD expression even within the same family.

What Causes HD?

Identification and localization of the HD gene (HTT) have enabled the determination of who will develop the disease through DNA mutation analysis of a blood sample. An accurate family history is essential, as the test is specific to HD. Brain imaging studies, such as computed tomography (CT) and magnetic resonance imaging (MRI) may show atrophy of the affected parts of the brain, especially the caudate nuclei and putamen (parts of basal ganglia), as well as generalized brain atrophy. DNA mutation analysis may be useful for confirming a diagnosis based on symptoms, predicting HD in an at-risk individual, or establishing a prenatal diagnosis in an at-risk pregnancy.

An autosomal dominant pattern of inheritance implies that only one copy of the mutated gene, from either parent, is sufficient to cause the disease. A parent with the HD gene mutation has a 50% chance of passing the gene to their offspring at each pregnancy. Males and females are equally affected. The HTT gene is located on the short arm of chromosome 4 (4p16.3). It synthesizes the protein huntingtin, which accumulates and is toxic in the brains of HD patients. The mutation in HD involves an expansion of the trinucleotide repeat (CAG). How exactly huntingtin protein causes harm in HD is not yet completely understood.

The HD gene mutation is known to be dynamic, meaning that it can change from one generation to another. If the CAG repeat sequence is expanded from the previous generation to the offspring, the affected offspring may develop an earlier and more severe course. This phenomenon is known as "anticipation." Anticipation most often occurs through transmission from an affected father.

Very rarely, an individual can develop HD who has no known family history of the disorder. Situations like this are thought to occur due to spontaneous mutations or from a missed or incorrect diagnosis in the previous generation.

How is Age Related to HD?

In the United States, the overall prevalence of HD is about 1 in every 10,000–20,000 persons. The disease typically begins in mid-adulthood, i.e., 30–55 years of age. However, juvenile-onset HD (JHD) occurs in about 10% of families, and it is nearly always inherited from a father who carries the HD gene mutation.

What Happens in HD?

The characteristic triad includes

1. physical symptoms (e.g., involuntary movements, restlessness, fidgety, loss of balance, awkward gait, poor coordination, dysarthria)
2. cognitive changes (e.g., memory loss, inability to multitask, poor calculations, disorganization)
3. emotional and behavioral disturbances (e.g., depression, apathy, paranoia, anger, withdrawal, anxiety)

Early symptoms may include personality changes, such as mood swings, irritability, apathy, depression, anger, or aggression. Early in the disease, cognitive decline may manifest as memory and learning difficulties, impaired judgment, and difficulty with driving, answering questions, or making decisions. As the disease progresses, concentration and focus on intellectual tasks become increasingly difficult. Weight loss, not due to decreased caloric intake, is a common feature of patients with HD.

Chorea may appear at various stages of the disease and begin as uncontrolled movements of the extremities, face, or trunk that worsen over time. Fidgety movements, restlessness, clumsiness, or imbalance may precede chorea. The movement component of HD is extremely variable, with some affected individuals experiencing only mild involuntary movements and others suffering from movements that interfere with daily function.

The disease can progress to the point where speech is slow and slurred (dysarthria) and vital functions, such as walking, self-care, eating, and eventually swallowing, may continue to decline. Affected individuals require increasing levels of care with disease progression, but many patients remain close to their family and friends, continue to be aware of their environment, and are able to express emotions.

Are There Medicines to Treat HD?

Currently, there is no cure for HD or a treatment that is able to slow or stop the progression. However, treatments are available to help manage some of the symptoms. Antipsychotic drugs may help to alleviate involuntary movements, hallucinations, delusions, and violent outbursts. Antipsychotic drugs, however, can have severe side effects, including stiffness and sedation, and for that reason are used in the lowest possible doses. Antidepressants are used for depression, and tranquilizers can help with severe mood swings. Studies are underway to determine if antioxidants and several other agents may provide neuroprotection and, therefore, prevent degeneration in HD.

Making healthy life choices clearly contributes to overall well-being, such as eating a nutritious diet, engaging in safe exercise, and maintaining connections with friends, family, and community. Special devices to assist in activities of daily living (ADLs), a special diet to aid in swallowing, and increasing calories to counteract weight loss may eventually require consideration.