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Huntington disease is a progressive brain
Adult-onset Huntington disease, the most common form of this disorder, usually appears in a person's thirties or forties. Early signs and symptoms can include irritability, depression, small involuntary movements, poor coordination, and trouble learning new information or making decisions. Many people with Huntington disease develop involuntary jerking or twitching movements known as chorea. As the disease progresses, these movements become more pronounced. Affected individuals may have trouble walking, speaking, and swallowing. People with this disorder also experience changes in personality and a decline in thinking and reasoning abilities. Individuals with the adult-onset form of Huntington disease usually live about 15 to 20 years after signs and symptoms begin.
A less common form of Huntington disease known as the juvenile form begins in childhood or adolescence. It also involves movement problems and mental and emotional changes. Additional signs of the juvenile form include slow movements, clumsiness, frequent falling, rigidity, slurred speech, and drooling. School performance declines as thinking and reasoning abilities become impaired. Seizures occur in 30 percent to 50 percent of children with this condition. Juvenile Huntington disease tends to progress more quickly than the adult-onset form; affected individuals usually live 10 to 15 years after signs and symptoms appear.
Huntington disease affects an estimated 3 to 7 per 100,000 people of European ancestry. The disorder appears to be less common in some other populations, including people of Japanese, Chinese, and African descent.
Mutations in the HTT gene cause Huntington disease. The HTT gene provides instructions for making a protein called huntingtin. Although the function of this protein is unclear, it appears to play an important role in nerve cells (neurons) in the brain.
The HTT mutation
An increase in the size of the CAG segment leads to the production of an abnormally long version of the huntingtin protein. The elongated protein is cut into smaller, toxic fragments that bind together and accumulate in neurons, disrupting the normal functions of these cells. The dysfunction and eventual death of neurons in certain areas of the brain underlie the signs and symptoms of Huntington disease.
This condition is inherited in an autosomal dominant pattern
As the altered HTT gene is passed from one generation to the next, the size of the CAG trinucleotide repeat often increases in size. A larger number of repeats is usually associated with an earlier onset of signs and symptoms. This phenomenon is called anticipation
Individuals who have 27 to 35 CAG repeats in the HTT gene do not develop Huntington disease, but they are at risk of having children who will develop the disorder. As the gene is passed from parent to child, the size of the CAG trinucleotide repeat may lengthen into the range associated with Huntington disease (36 repeats or more).
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Watch this video for advice on Huntington's disease and the importance of getting tested.
HD affects the whole brain, but certain areas are more vulnerable than others. Pictured above in blue is the striatum – an area deep in the brain that plays a key role in movement, mood, and behavior control. The striatum is the part of the brain that is most affected by HD.
What Is Huntington’s Disease?
Huntington’s disease (HD) is a brain disease that is passed down in families from generation to generation. It is caused by a mistake in the DNA instructions that build our bodies and keep them running. DNA is made up of thousands of genes, and people with HD have a small error in one gene, called huntingtin. Over time this error causes damage to the brain and leads to HD symptoms.
HD causes deterioration in a person’s physical, mental, and emotional abilities, usually during their prime working years, and currently has no cure. Most people start developing symptoms during adulthood, between the ages of 30 to 50, but HD can also occur in children and young adults (known as juvenile HD or JHD). HD is known as a family disease because every child of a parent with HD has a 50/50 chance of inheriting the faulty gene. Today, there are approximately 41,000 symptomatic Americans and more than 200,000 at-risk of inheriting the disease.
Symptoms of Huntington’s Disease
The symptoms of HD can vary a lot from person to person, but they usually include:
- Personality changes, mood swings & depression
- Forgetfulness & impaired judgment
- Unsteady gait & involuntary movements (chorea)
- Slurred speech, difficulty in swallowing & significant weight loss
Most people with HD experience problems with thinking, behavior, and movements. Symptoms usually worsen over the course of 10 to 25 years and affect the ability to reason, walk, and talk. Early on, a person with HD or their friends and family may notice difficulties with planning, remembering, and staying on task. They may develop mood changes like depression, anxiety, irritability, and anger. Most people with HD become “fidgety” and develop movements of the face and limbs known as chorea, which they are not able to control.
Because of the uncontrolled movements (chorea), a person with HD may lose a lot of weight without intending to, and may have trouble walking, balancing, and moving around safely. They will eventually lose the ability to work, drive, and manage tasks at home, and may qualify for disability benefits. Over time, the individual will develop difficulty with speaking and swallowing, and their movements will become slow and stiff. People with advanced HD need full-time care to help with their day-to-day activities, and they ultimately succumb to pneumonia, heart failure or other complications. The symptoms of HD are sometimes described as having ALS, Parkinson’s and Alzheimer’s – simultaneously.
The Huntingtin Gene & Protein
The DNA error that causes HD is found in a gene called huntingtin. This gene was discovered in 1993. Everyone has the huntingtin gene, but only those that inherit the mistake, known as the HD mutation, will develop HD and risk passing it on to their children. Genes are made up of the nucleotide “letters” A,G,C, and T, which form a code that is read in groups of three. HD is caused by a stretch of the letters C-A-G in the huntingtin gene which repeat over and over, too many times…CAGCAGCAGCAGCAG. This is known as a CAG repeat expansion. In the huntingtin gene, most people have around 20 CAG repeats, but people with HD have around 40 or more. Every person who has this CAG repeat expansion in the HD gene will eventually develop the disease, and each of their children has a 50% chance of developing HD.
Our genes are like an instruction manual for making proteins, the machines that run everything in our bodies. The huntingtin gene (DNA) contains instructions that are copied into a biological message (RNA) which makes the huntingtin protein. The huntingtin protein is very large and seems to have many functions, especially as the brain is developing before birth, but it is not fully understood. We know that the extra CAG repeats in people with HD cause the huntingtin protein to be extra-long and difficult to maintain, which makes it difficult for it to do its job. Over many years, this “mutant” huntingtin protein forms clumps in brain cells, and causes them to become damaged and die. The most vulnerable part of the brain in HD is called the striatum, and it controls movement, mood, and memory. Damage to the striatum over time is what causes the symptoms of HD.
Treating Huntington’s Disease
There is currently no cure or treatment which can halt, slow or reverse the progression of the disease. However, there are many treatments and interventions that can help to manage HD symptoms. A neurologist, psychiatrist, or nurse with expertise in HD may prescribe medications to ease anxiety and depression, help with troublesome
behaviors, and calm uncontrolled movements. A psychologist or social worker can provide individual or group counseling. Physical and occupational therapists can work with patients and families to develop strength, move safely, and adjust the home environment and activities as needed. Speech language pathologists and nutritionists can help with communication, eating and swallowing safely, and combating weight loss. Clinician researchers may suggest participation in HD clinical trials.
Social and community support is an important part of HD care. Family, friends, loved ones, and companions often assume many of the HD person’s former responsibilities and help with daily activities and care routines when they can no longer do so themselves. Caregivers and kids may also need support for the challenges and stresses that come with HD.