It happens when a faulty gene causes toxic proteins to collect in the brain.
The first signs normally appear between the ages of 30 and 50 years.
- Huntington's disease (HD) is an inherited disease that attacks nerve cells gradually over time.
- The disease happens when a faulty gene makes an abnormal version of the huntingtin protein.
- Early symptoms may include mood swings, clumsiness, and unusual behavior.
- During the later stages of the disease, choking becomes a major concern.
- There is currently no cure, but medications may help relieve symptoms.
What is Huntington's?
Huntington's disease (HD) is a neurological condition. It is an inherited disease that happens due to faulty genes. Toxic proteins collect in the brain and cause damage, leading to neurological symptoms.
As parts of the brain deteriorate, this affects movement, behavior, and cognition. It becomes harder to walk, think, reason, swallow, and talk. Eventually, the person will need full-time care. The complications are usually fatal.
There is currently no cure, but treatment can help with symptoms.
Huntington's usually starts between the ages of 30 and 50 years. Changes in mood and thinking can be an early sign.
Signs and symptoms are most likely to appear between the ages of 30 and 50 years, but they can occur at any age. They tend to worsen over 10 to 20 years.
Eventually the Huntington's disease or its complications are fatal.
The key symptoms include:
- personality changes, mood swings, and depression
- problems with memory and judgment
- unsteady walk and uncontrollable movements
- difficulty speaking and swallowing, and weight loss
How signs and symptoms evolve can vary between individuals. In some people, depression occurs before motor skills are affected. Mood swings and unusual behavior are common early signs.
Early signs and symptoms
Early symptoms may not be recognized if HD has not previously occurred in the family. It can take a long time to reach a diagnosis.
Initial signs and symptoms include:
- slight uncontrollable movements
- small changes in coordination and clumsiness
- slight signs of mood and emotional change
- lack of focus, slight concentration problems, and difficulty functioning, for example, at work
- lapses in short-term memory
The person may lose motivation and focus, and appear lethargic and lacking in initiative.
Other possible signs of HD may include stumbling, dropping things, and forgetting people's names. However, most people do these from time to time.
The middle and later stages
In time, symptoms become more severe.
These include physical changes, loss of motion control, and emotional and cognitive changes.
The person may experience:
- difficulty speaking, including looking for words and slurring
- weight loss, leading to weakness
- difficulty eating and swallowing, as the muscles in the mouth and diaphragm may not work properly
- risk of choking, especially in the later stages
- uncontrollable movements
There may be uncontrollable body movements, including:
- uncontrollable movements of the face
- jerking of parts of the face and the head
- flicking or fidgety movements of the arms, legs, and body
- lurching and stumbling
As HD progresses, the uncontrollable movements occur more often and with usually with more intensity. Eventually they may become slower as the muscles become more rigid.
These may alternate rather than occurring consistently.
- antisocial behavior
- lack of emotion becomes more apparent
- cognitive changes
There may be:
- a loss of initiative
- a loss of organizational skills
- difficulty focusing
- problems with multitasking
The later stage
Eventually, the person will no longer be able to walk or talk, and they will need full nursing care.
However, they will usually understand most of what is being said and will be aware of friends and family members.
The inability to do things that used to be easy can lead to frustration and depression.
Weight loss can make the symptoms worse and weaken the patient's immune system, making them more vulnerable to infections and other complications.
HD itself is not usually fatal, but choking, pneumonia or another infection can be.
Throughout all stages, it is important to adjust the patient's diet to ensure adequate food intake.
HD is caused by a faulty gene (mhTT) on chromosome number 4.
A normal copy of the gene produces huntingtin, a protein. The faulty gene is larger than it should be. This leads to excessive production of cytosine, adenine, and guanine (CAG), the building blocks of DNA. Normally, CAG repeats between 10 and 35 times, but in HD, it repeats from 36 to 120 times. If it repeats 40 times or more, symptoms are likely.
This change results in a larger form of huntingtin. This is toxic, and, as it accumulates in the brain, it causes damage to brain cells.
Some brain cells are sensitive to the larger form of huntingtin, especially those related to movement, thinking, and memory. It undermines their function and eventually destroys them. Scientists are not sure exactly how this happens.
How is it passed on?
HD is known as an autosomal dominant disorder. This means that only one copy of the faulty gene, inherited from either the mother or the father, is necessary to produce the disease.
A person with the gene has one good copy of the gene and one faulty copy of the gene. Any offspring will inherit either the good copy or the faulty one. The child who inherits the good copy will not develop HD. The child who inherits a faulty copy will.
Each child has a 50 percent chance of inheriting the faulty gene. If they inherit the faulty gene, each of their children will have a 50 percent chance of inheriting it. HD can affect several generations.
A person who does not inherit the faulty gene will not develop HD and cannot pass it on to their children. A child who inherits the faulty gene will develop HD if they reach the age when symptoms are due to emerge.
Around 10 percent of cases of HD start before the age of 20 years. This is known as juvenile HD (JHD).
The symptoms are different, and can include leg stiffness, tremors, and regression in learning.
Between 30 and 50 percent of people with JHD have seizures.
HD is currently incurable. There is no treatment that can reverse its progression or slow it down.
However, some symptoms can be managed with medication and therapies.
Tetrabenazine (Xenazine) is approved by the Food and Drug Administration (FDA) to treat the jerky, involuntary movements, or chorea, associated with HD.
Side effects include depression and suicidal thoughts or actions.
- feeling sad and having crying spells
- losing interest in friends and previously enjoyable activities
- sleeping more or less than usual and feeling tired
- feeling guilty or unimportant
- feeling more irritable, angry, or anxious than before
- eating less than usual, possibly with weight loss
- having difficulty focusing
- thinking about harming oneself or ending one's life
Any of these symptoms or other mood changes should be reported to the doctor at once.
Anyone who has a diagnosis of depression, especially with suicidal thoughts, should not use tretrabenazine.
Drugs to control movements, outbursts, and hallucinations may include:
- clonazepam (Klonopin)
- clozapine (Clorazil)
These drugs may cause sedation, as well as stiffness and rigidity.
For depression and some obsessive-compulsive features that can appear with HD, the doctor may prescribe:
- fluoxetine (Prozac, Sarafem)
- sertraline (Zoloft)
- nortriptyline (Pamelor)
Lithium may help with extreme emotions and mood swings.
Speech therapy can help patients find ways to express words and phrases and communicate in a more effective way.
Physical and occupational therapy
A physical therapist can help improve muscle strength and flexibility, leading to better balance and a reduced the risk of falling.
An occupational therapist can help the patient develop strategies for coping with concentration and memory problems, as well as making the home safer.
The doctor will examine the patient and ask about family and medical history, and symptoms, such as recent emotional changes.
If they suspect HD, they will refer the patient to a neurologist.
Imaging tests, such as a CT or MRI scan, are sometimes used to identify changes in the patient's brain structure, and to rule out other disorders.
Genetic testing may be recommended to confirm a diagnosis.
HD has a major emotional, mental, social, and economic impact on the lives of the individual and their families. After diagnosis, a person will normally live for 15 to 20 years, but the duration ranges from 10 to 30 years.
A person with JHD will probably live around 10 years. This form progresses more quickly.
The cause of death is often a complication, such as pneumonia or choking.
While there is currently no cure, some therapies can help people to manage the condition and improve quality of life.
Hope for the future?
In the future, scientists hope that gene therapy will find a solution to this disease. Researchers have been looking for ways to use gene therapy for cure, slow, or prevent HD.
One hopeful strategy is to use molecules known as synthetic small interfering RNAs (siRNAs) to suppress protein production from the faulty gene. This would stop the toxic Huntingtin protein from collecting and causing symptoms.
However, the challenge that remains is how to deliver the siRNAs to the appropriate brain cells, so that they can be effective.
In 2017, scientists from Emory University suggested that CRISPR/Cas9 techniques, which involve "cutting and pasting" DNA, could help prevent HD in future.
When the researchers engineered the faulty gene in mice, they found "significant improvements" after 3 weeks. Most of the traces of the damaging protein had gone, and the nerve cells showed signs of healing themselves.
Much more research is needed before this can be applied to humans, however.
Organizations such as HDSA offer support for people with HD and their families.
Genetic testing for HD became possible in 1993. Anyone with a family history of HD can ask their doctor about genetic testing, to find out whether or not they carry the defective gene.
Some people prefer to find out if they have the gene, and if they are likely to develop symptoms, while other would rather not know. A genetic counselor can help with making the decision.
HD, genetics, and pregnancy
If a couple wish to have a child, and one parent has the faulty gene, it is possible to have in-vitro fertilization (IVF) treatment. The embryo is then genetically tested in a laboratory and is only implanted into the woman if it does not have the faulty gene.
Genetic testing can also be carried out during pregnancy, if there is a family history of HD. This can be done using chorionic villus sample (CVS) at 10 to 11 weeks, or through an amniocentesis at 14 to 18 weeks.