Huntington disease

Huntington disease (HD) is a progressive disorder that causes motor, cognitive, and psychiatric signs and symptoms. On average, most people begin developing features of HD between ages 35 and 44. Signs and symptoms vary by stage and may include:^[1][2]

Early stage:

• Behavioral disturbances
• Clumsiness
• Moodiness
• Irritability
• Paranoia
• Apathy
• Anxiety
• Hallucinations
• Abnormal eye movements
• Depression
• Impaired ability to detect odors

Middle stage:

• Dystonia
• Involuntary movements
• Trouble with balance and walking
• Chorea with twisting and writhing motions
• Unsteady gait (style of walking)
• Slow reaction time
• General weakness
• Weight loss
• Speech difficulties
• Stubbornness

Late stage:

• Rigidity (continual tension of the muscles)
• Bradykinesia (difficulty initiating and continuing movements)
• Severe chorea
• Serious weight loss
• Inability to speak
• Inability to walk
• Swallowing problems
• Inability to care for oneself

There is also a less common, early-onset form of HD which begins in childhood or adolescence. For more information on this form, please visit GARD's juvenile Huntington disease Web page.

Huntington disease (HD) is progressive, eventually leading to disability and death (usually from a coexisting illness or infection). However, the disease affects everyone differently; the age of onset, specific symptoms, and rate of progression varies for each person with HD.

While the symptoms of HD are well-characterized, their progression (especially in the early and middle stages) remains unpredictable. With the approach of late-stage HD, affected people have speech difficulty and weight loss. In the late stage, affected people lose bowel and bladder control.^[3]

The duration of the disease (from onset until death) varies considerably, with an average of approximately 19 years. Most people with HD survive for 10-25 years after the onset of symptoms. The average age at death ranges from 51-57 years, but the range may be broader. In a large study, pneumonia and cardiovascular (heart) disease were the most common primary causes of death.^[4]

The length of the CAG repeat (the type of mutation in the HTT gene responsible for HD) is the most important factor that determines age of onset of HD. However, there is still a lot of variability. Both genetic and environmental factors are thought to play a role on the age of onset in people with a mutation. Inheritance through the father can lead to more repeat expansion and earlier onset through succeeding generations, a phenomenon called anticipation.^[4]

People with HD, family members, and/or caregivers with specific questions about prognosis should speak with their health care provider.

Huntington disease (HD) is inherited in an autosomal dominant manner.^[1] This means that having a change (mutation) in only one of the 2 copies of the HTT gene is enough to cause the condition. When a person with HD has children, each child has a 50% (1 in 2) chance to inherit the mutated gene and develop the condition.

Most people with HD have an affected parent. The family history can sometimes appear negative for various reasons even though a parent carries, or carried, a mutation in the HTT gene. In rare cases, HD is caused by a new (de novo) mutation in the HTT gene, in which case the disease occurs for the first time in the affected person and is not inherited from a parent.^[1]

As HD is passed through generations, the size of the mutation in the HTT gene (called a trinucleotide repeat) often increases. A longer repeat in the HTT gene may cause earlier onset of symptoms. This phenomenon is called anticipation.^[5]

Huntington disease (HD) does not occur in one generation, skip the next, and then reoccur in a subsequent generation. However, HD may appear to skip a generation for one of the following reasons:

• Failure to recognize the disease in family members
• Early death of a parent before the onset of symptoms
• The presence of an intermediate allele (an allele with 27-35 CAG repeats) or an HTT allele with reduced penetrance (with 36-39 CAG repeats), which may or may not result in HD in an asymptomatic parent
• Late onset of the disease in an affected parent^[1]

All people who inherit an allele with more than 40 CAG repeats will develop HD. Those with 36-39 repeats are considered at risk of developing the disease.^[1]

People that do not inherit the mutated gene from an affected parent are not at risk to develop HD, and because they don't carry the mutated gene, they are also not at risk to pass it on to their children.

Genetic counseling is strongly recommended for people with questions about the risk of HD for themselves or family members, or people who are considering genetic testing for a family history of HD.