Huntington's disease (HTT CAG expansion): genetics, predictive testing and support

The NHS describes Huntington's disease as an inherited condition that affects movement, thinking and mood, gets worse over time and cannot currently be cured, although there are treatments for symptoms. The altered gene damages certain areas of the brain. The NHS says early symptoms can include difficulty concentrating and planning, memory problems, low mood, depression and anxiety, irritability or impulsiveness, small uncontrollable twitching or jerking movements called chorea, and clumsiness.

The NHS Genomics Education Programme sorts the course into stages. Early signs include chorea, clumsiness, agitation, irritability, anxiety, apathy and mild cognitive change. In the middle stage dystonia, weight loss, speech and swallowing difficulty and slowed voluntary movement appear. In late disease there is dementia, rigidity, inability to walk or speak and inability to care for oneself. It gives the median survival after onset as 15 to 18 years.

Mood and behaviour changes often come before the movement disorder. The programme notes that it is common for people to have been treated for anxiety or depression before the diagnosis is made, and that cognitive and psychiatric problems are often present at diagnosis although most people present with a movement problem.

Inside the HTT gene is a stretch where the three DNA letters C, A and G repeat in a row. Everyone has some repeats. The NHS Genomics Education Programme explains that Huntington's disease occurs when this number is expanded, and that there is a broad link between the number of repeats and when symptoms appear. At the level of an individual, however, the programme cautions that repeat size does not correlate well with age of onset, symptoms or progression, which can differ considerably even within one family.

Because the disease is autosomal dominant, a person has one working copy of HTT and one expanded copy, and passes either on to a child by chance. The NHS puts it as a 1 in 2 chance for each child of a parent who carries the altered gene. Siblings and parents of an affected person share the same one in two starting chance.

Expansions of 55 CAG repeats or more are at risk of early-onset symptoms. Juvenile Huntington's disease begins before 20, is very rare under 10, and can look different: developmental delay, obsessive-compulsive behaviour, early dystonia, stiffness, and seizures in 30% to 35%, with chorea appearing later.

The NHS says that if one of your parents has Huntington's disease or you have symptoms, you can choose to have a genetic test, that you will usually need to be 18 or over, and that it is your choice. As Huntington's disease cannot currently be prevented, some people choose not to be tested, especially if they have no symptoms. A GP can arrange an appointment with a genetic counsellor to help decide.

For people without symptoms, the NHS Genomics Education Programme says predictive (presymptomatic) testing is offered through clinical genetics services only, because of the implications for relationships, finances and psychological wellbeing. A series of appointments is recommended, including a mental health assessment, to support the decision. A positive result does not say when symptoms will start, and a negative result in someone at risk shows they did not inherit the expanded gene.

The NHS says living with the condition or having a parent with it can affect decisions such as planning for the future and starting a family.

There is currently no cure and no treatment that stops the symptoms getting worse, the NHS says. The aim is to help manage symptoms and stay comfortable and independent for as long as possible. The NHS lists treatment for depression such as antidepressants and talking therapies, medicines for mood and behaviour changes, medicines for chorea, physiotherapy, occupational therapy and speech and language therapy, and notes that a care plan is created with a team of professionals.

The NHS Genomics Education Programme describes multidisciplinary management with neurologists, neuropsychiatrists, community mental health teams, geneticists, physiotherapists, speech and language therapists, dietitians and occupational therapists, and says a wide range of potential therapies are under investigation. Most people live for many years after symptoms start but eventually need support with daily living, according to the NHS.

The Huntington's Disease Association is the national charity named by the NHS for help and support for people with Huntington's disease, families and carers, with local support near you. The NHS also points families towards social care options if help with daily living is needed.

Families affected by Huntington's disease often face several decisions in parallel: whether to test, whom to tell, and how to plan. Clinical genetics teams are used to supporting these conversations, including with relatives who choose not to know.