Huntington's Disease

What causes Huntington's disease

The HTT gene contains a section where three DNA letters, CAG, repeat. Most people have fewer than 27 repeats. In Huntington's disease, the section is expanded, producing an abnormal huntingtin protein that gradually damages nerve cells, especially in the basal ganglia (the striatum) and later the cortex.

Longer repeats usually mean earlier onset. Repeats can grow when passed on, especially from fathers, which is why juvenile HD is more often inherited from the father.

HD affects roughly 1 in 10,000 people of European ancestry and is less common in other populations.

Symptoms

Symptoms vary, and psychiatric or thinking changes often appear years before movement problems.

Movement

• chorea: brief, irregular, flowing movements of the face, hands and body, often appearing restless or fidgety at first
• clumsiness, falls and an unsteady, dance-like walk
• abnormal eye movements
• later: stiffness, slowness, dystonia (twisting postures)
• slurred speech and difficulty swallowing

Thinking (cognitive)

• difficulty planning, organizing and multitasking
• slowed thinking
• trouble starting tasks and shifting attention
• lack of awareness of one's own symptoms
• eventually dementia, though language and recognition of people are often preserved longer than in Alzheimer's disease

Mood and behavior

• depression, very common
• irritability, outbursts and aggression
• apathy, the most common behavioral symptom
• anxiety and obsessive-compulsive behaviors
• impulsivity and, less often, psychosis
• increased suicide risk (suicidal thoughts need urgent help)

Juvenile Huntington's disease

When HD begins before age 20, usually with long repeats, stiffness and slowness, similar to Parkinson's disease, are more prominent than chorea. Children may have learning difficulties, behavior problems and seizures.

Stages

Death typically occurs 15 to 20 years after symptom onset, most often from pneumonia, choking or complications of falls.

Diagnosis

• Neurological exam for chorea, eye movements, coordination and cognition.
• Family history, although some people are unaware of an affected parent because of early death, misdiagnosis or non-paternity.
• Genetic blood test measuring CAG repeats confirms the diagnosis.
• Brain MRI may show shrinkage of the caudate nucleus, but imaging is not needed for diagnosis.

Predictive genetic testing

People at risk who have no symptoms can choose to be tested. International guidelines recommend genetic counseling before and after testing, usually over several sessions, because the result has major emotional, family, employment and insurance implications. Testing is generally not offered to minors without symptoms.

Family planning

Options for people with HD or at risk include prenatal testing and in vitro fertilization with preimplantation genetic testing to select embryos without the expansion.

Treatment

There is no treatment yet that slows progression, though gene-targeting therapies are being studied in clinical trials.

Movement symptoms

• VMAT2 inhibitors (tetrabenazine, deutetrabenazine, valbenazine) reduce chorea. They can worsen depression, so mood is monitored.
• Antipsychotics, which also treat conditions such as bipolar disorder, can reduce chorea and help with agitation or psychosis.
• Physical therapy for balance, walking and fall prevention.

Mood and behavior

• antidepressants for depression, anxiety and irritability
• mood stabilizers or antipsychotics for aggression or psychosis
• counseling and support for the person and family

Daily living

• Speech and swallowing therapy: safer swallowing techniques and modified food textures.
• Nutrition: many people need high-calorie diets because chorea burns energy; feeding tubes are discussed in later stages.
• Occupational therapy: home adaptations and routines.
• Advance care planning while the person can participate.
• Multidisciplinary HD clinics, such as HDSA Centers of Excellence in the US.

Frequently asked questions

What are the early signs of Huntington's disease?

Early signs often include mood changes such as depression or irritability, difficulty planning and organizing, clumsiness, and small involuntary movements that look like fidgeting. These may appear years before obvious chorea.

Is Huntington's disease always inherited?

Almost always. Each child of a person with HD has a 50% chance of inheriting the gene. Occasionally, HD appears without a known family history, because a parent died early, was misdiagnosed, or had an intermediate repeat that expanded in the next generation.

How long do people live with Huntington's disease?

On average, people live about 15 to 20 years after symptoms start, though this varies. Juvenile HD often progresses faster. Pneumonia, choking and complications of falls are common causes of death.

Is there a cure for Huntington's disease?

There is no cure yet. Medicines help control chorea, depression and behavior, and therapies support function and safety. Several treatments that target the huntingtin gene or protein are in clinical trials.