Huntington's disease

Huntington disease (HD) is an  condition that causes progressive degeneration of neurons in the brain. Signs and symptoms usually develop between ages 35 to 44 years and may include uncontrolled movements, loss of intellectual abilities, and various emotional and psychiatric problems. People with HD usually live for about 15 to 20 years after the condition begins. It is caused by changes () in the HTT gene and is inherited in an  manner. Treatment is based on the symptoms present in each person and may include various medications.

Huntington's disease (5880985560)

Symptoms

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:

Early stage:

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

On Chorea with photo

Middle stage:

• 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.

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources.

Medical Terms	Other Names	Learn More: HPO ID
30%-79% of people have these symptoms
Abnormality of movement	Movement disorder [ more  ]	0100022
Abnormality of the voice	Voice abnormality	0001608
Behavioral abnormality	Behavioral changes [ more  ]	0000708
Cerebral cortical atrophy	Decrease in size of the outer layer of the brain due to loss of brain cells	0002120
	Dementia, progressive [ more  ]	0000726

Cause

Huntington disease (HD) is caused by a change () in the HTT . This gene gives instructions for making a  called huntingtin. The exact function of this protein is unclear, but it appears to be important to nerve  (neurons) in the brain.

The HTT gene mutation that causes HD involves a  segment known as a CAG . This segment is made up of three DNA building blocks that repeat multiple times in a row. The CAG segment in a normal HTT gene repeats about 10 to 35 times. In people with HD, it may repeat from 36 to over 120 times. People with 36 to 39 CAG repeats (an intermediate size) may or may not develop HD, while people with 40 or more repeats almost always develop HD.

Inheritance

Huntington disease (HD) is  in an  manner.[2] This means that having a change () in only one of the 2 copies of the HTT  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  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 () 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.

As HD is passed through generations, the size of the mutation in the HTT gene (called a ) often increases. A longer repeat in the HTT gene may cause earlier onset of symptoms.

Diagnosis

A diagnosis of Huntington disease is typically suspected in people with characteristic signs and symptoms of the condition and a  consistent with  inheritance. The diagnosis can then be confirmed with  that identifies a specific type of change () in the HTT.

Testing Resources

• The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
  
• The Division of Neurogenetics at the University of Washington is a tertiary specialty that provides clinical services to adults in the general public as well as training. They have created a booklet entitled, "Huntington Disease: Making an Informed Choice,  that can be downloaded at no charge.
• Orphanet lists international laboratories offering diagnostic testing for this condition.

Treatment

Unfortunately, there is currently no cure for Huntington disease (HD). The current goal of treatment is to slow down the course of the disease and help affected people function for as long and as comfortably as possible.

Current treatment strategies involve the use of various medications to treat specific symptoms such as abnormal movements and behaviors. Depression and suicide are more common among affected people, so caregivers should monitor for associated symptoms and seek help if necessary. As symptoms of the disease worsen, affected people need more assistance, supervision, and care.

FDA-Approved Treatments

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

• Deutetrabenazine (Brand name: Austedo) - Manufactured by Teva Branded Pharmaceutical Products R&D, Inc. FDA-approved indication: Treatment of chorea associated with Huntington’s disease. National Library of Medicine Drug Information Portal
• Tetrabenazine (Brand name: Xenazine®) - Manufactured by Lundbeck Inc. FDA-approved indication: Treatment of chorea associated with Huntington's disease National Library of Medicine Drug Information Portal

Prognosis

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.

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.

The length of the CAG repeat (the type of  in the HTT  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  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 .

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

Classification	ICD-10: G10 , F02.2 OMIM: 143100 MeSH: D006816 DiseasesDB: 6060
External resources	MedlinePlus: 000770 eMedicine: article/1150165 Orphanet: 399

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