Understanding HD – Level 2 – European Huntington Association

What is Huntington’s Disease?

Everyone has a gene that serves as an instruction to make a protein called Huntingtin. In a person with Huntington’s disease this gene is changed from normal to a faulty version. We call it a mutated Huntingtin gene. The faulty gene causes the production of a harmful Huntingtin. Over time, the faulty Huntingtin is causing brain cells to malfunction and ultimately die.

Although we have Huntingtin in all cells in our body, the faulty gene causes the most harm in specific key areas of the brain (the so-called basal ganglia and the cortex). These areas are vital in managing emotional, behavioral, cognitive (thinking and planning), and motor (movement) abilities. There is currently no cure or way to stop the disease, but treatments can help manage symptoms. A lot of research and studies are ongoing, aiming to reduce mutant Huntingtin levels or help brain cells compensate and function better.

What Does HD Do to the Brain and Cells?

The HD mutation causes the Huntingtin protein to misfold and accumulate inside the brain cells. The accumulation increases over the years and is causing more malfunctions. It reduces the cells’ ability to produce energy, which is vital for them to operate, and it also reduces the cells’ ability to communicate with each other. We still don’t know how all the different functions within the cell are influenced by the mHTT protein (harmful, mutant, Huntingtin protein), but ultimately, brain cells die from the intoxication.

It is important to understand that the changes one can see in a person with Huntington’s Disease are caused by brain changes and damage. The regions of the brain particularly vulnerable to mHTT are involved in movement control, decision-making, emotional regulation, and memory. This gradual damage explains why symptoms worsen over many years.

Genetic Basis: HTT Gene, CAG Repeats, and Heredity

The number of the C-A-G repeats in the Huntingtin gene varies from person to person. In relation to Huntington’s disease, the number of C-A-G repeats is divided into categories:

26 or fewer repeats: This is the normal range, and the person will not develop HD
27–35 repeats: This is a relatively high number of CAG repeats. The person will not develop HD him/herself. However, this range of CAG repeats is unstable and is prone to variation during transmission to subsequent generations; so it may have implications for future generations. This range of CAG repeats is also known as the intermediate range.
36–39 repeats: This CAG repeat range is considered an expansion with incomplete or reduced penetrance. This means the gene expansion can cause Huntington’s disease — usually later in life — but not everyone in this range will develop symptoms.
40 or more repeats: confirm the HD mutation and mean the person will develop Huntington’s disease at some point in life.
60 or more: People with a very high number of repeats will develop HD early in life (typically before the age of 20). This variant of Huntington’s disease is called juvenile-onset HD (the term pediatric Huntington’s disease is reserved for all patients with manifest disease who are still below the age of 18 years old). Usually, in this variant, the affected parent is the father.

Huntington’s disease is called dominant. That is because if you inherit the mutated gene from your parent with the disease, it will dominate the normal gene you inherit from your other parent. The number of repeats can change when passed from parent to child. Siblings can have different numbers of CAG repeats. And the number can vary when passed on to the next generation, thereby influencing the age of onset (anticipation phenomenon).

Children do not necessarily develop the disease in the same pattern as their parents. The same is the case between siblings. Learning about genetic risk can raise difficult questions about family planning and emotional support. Genetic counselling should be offered.

When Do Symptoms Start and Why Are They So Different?

The age when HD symptoms show up is mainly affected by the number of CAG repeats, but it’s not the only factor. Things like other genetic modifiers, lifestyle choices, environment, and overall health also have an impact.

Juvenile HD (onset before age 20): often includes stiffness, walking problems, and learning difficulties; progression is typically faster
Adult-onset HD (often in 30s–50s): more likely to begin with mood or cognitive changes before motor symptoms

Variability is common. One person might experience primarily emotional changes (like depression or anxiety), while another might have mostly motor symptoms. Some experience rapid decline, while others live many years with manageable symptoms. This diversity makes personalized care essential; support must be adapted to each individual.

What Are the Symptoms and How Do They Progress?

Symptoms of HD can be grouped into three main categories:

Motor symptoms
- Involuntary movements (often chorea), clumsiness, balance problems
- Later: muscle rigidity, difficulty walking, speaking, or swallowing
Cognitive symptoms
- Slowed thinking, poor concentration, forgetfulness
- Impaired problem-solving, trouble planning or multitasking
Psychiatric symptoms
- Depression, suicidality, anxiety, irritability, aggression, sleep disturbances
- Apathy, lack of motivation, sometimes obsessive behaviors or hallucinations

In fact, individuals with Huntington’s disease almost always, at a certain point in time, also tend to lose weight progressively. In part it is due to an increase in the energy spending and to some extent because of the swallowing difficulties.

HD typically progresses in three stages:

Early stage: mild cognitive or mood changes, slight coordination problems, minimal impact on daily functioning
Middle stage: increasing motor dysfunction, speech and swallowing difficulties, more dependence on others
Late stage: severe movement problems, full dependency, limited communication, but often retained awareness

Progression can vary from person to person but usually occurs over 15 to 20 years. Support for caregivers is very important as the disease progresses.

How Can I Take Care of Myself Along the Way?

Although there is no effective treatment, many tools and strategies help people live meaningful lives. Management should be personalized and may include:

Medications for chorea and other disorders of movement, mood disorders, anxiety, and sleep problems
Therapies:
- Physical therapy to maintain balance and mobility
- Occupational therapy to adapt activities of daily living
- Speech and swallowing therapy
Mental health care: psychological support for both patients and caregivers
Nutrition: High-calorie, balanced diets to counter weight loss and support energy
Social and legal planning: early preparation of care decisions, financial planning, and medical directives

Staying socially active, participating in clinical research, and building a care network can all help maintain dignity and quality of life. Access to professional support and peer groups can make a big difference for both patients and families.

Is this a bit too detailed? You can always head back to our simplified overview.

Ready to continue? Our next chapter covers how the gene is identified.

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