• Huntington's disease

    Huntington's disease

    • Huntington's disease (HD)
      Synonyms Huntington's chorea
      Several neurons colored yellow and having a large central core with up to two dozen tendrils branching out of them, the core of the neuron in the foreground contains an orange blob about a quarter of its diameter
      An edited microscopic image of medium spiny neurons (yellow) with nuclear inclusions (orange), which occur as part of the disease process, image width 360 µm
      Classification and external resources
      Specialty neurology
      ICD-10 G10, F02.2
      ICD-9-CM 333.4, 294.1
      OMIM 143100
      DiseasesDB 6060
      MedlinePlus 000770
      eMedicine article/1150165 article/792600 article/289706
      Patient UK Huntington's disease
      MeSH D006816
      Orphanet 399

      Huntington's disease (HD), also known as Huntington's chorea, is an inherited disorder that results in death of brain cells. The earliest symptoms are often subtle problems with mood or mental abilities. A general lack of coordination and an unsteady gait often follow. As the disease advances, uncoordinated, jerky body movements become more apparent. Physical abilities gradually worsen until coordinated movement becomes difficult and the person is unable to talk. Mental abilities generally decline into dementia. The specific symptoms vary somewhat between people. Symptoms usually begin between 30 and 50 years of age, but can start at any age. The disease may develop earlier in life in each successive generation. About 8% of cases start before the age of 20 years and typically present with symptoms more similar to Parkinson's disease. People with HD often underestimate the degree of their problems.

      HD is typically inherited from a person's parents, with 10% of cases due to a new mutation. The disease is caused by an autosomal dominant mutation in either of an individual's two copies of a gene called Huntingtin. This means a child of an affected person typically has a 50% chance of inheriting the disease. The Huntingtin gene provides the genetic information for a protein that is also called "huntingtin". Expansion of CAG (cytosine-adenine-guanine) triplet repeats in the gene coding for the Huntingtin protein results in an abnormal protein, which gradually damages cells in the brain, through mechanisms that are not fully understood. Diagnosis is by genetic testing, which can occur at any point in time, regardless of whether or not symptoms are present. This fact raises several ethical debates: the age at which an individual is considered mature enough to choose testing; whether parents have the right to have their children tested; and managing confidentiality and disclosure of test results.

      Reported rates of behavioral symptoms in Huntington's disease
      Irritability 38–73%
      Apathy 34–76%
      Anxiety 34–61%
      Depressed mood 33–69%
      Obsessive and compulsive 10–52%
      Psychotic 3–11%
      Classification of the trinucleotide repeat, and resulting disease status, depends on the number of CAG repeats
      Repeat count Classification Disease status Risk to offspring
      <26 Normal Will not be affected None
      27–35 Intermediate Will not be affected Elevated but <<50%
      36–39 Reduced Penetrance May or may not be affected 50%
      40+ Full Penetrance Will be affected 50%

      • 40 or more CAG repeats: full penetrance allele (FPA). A "positive test" or "positive result" generally refers to this case. A positive result is not considered a diagnosis, since it may be obtained decades before the symptoms begin. However, a negative test means that the individual does not carry the expanded copy of the gene and will not develop HD. The test will tell a person who originally had a 50 percent chance of inheriting the disease if their risk goes up to 100 percent or is eliminated. A person who tests positive for the disease will develop HD sometime within their lifetime, provided he or she lives long enough for the disease to appear.
      • 36 to 39 repeats: incomplete or reduced penetrance allele (RPA). It may cause symptoms, usually later in the adult life. There is a maximum risk of 60% that a person with an RPA will be symptomatic at the age of 65 years, and a 70% risk of being symptomatic at the age of 75 years.
      • 27 to 35 repeats: intermediate allele (IA), or large normal allele. It is not associated with symptomatic disease in the tested individual, but may expand upon further inheritance to give symptoms in offspring.
      • 26 or fewer repeats: Not associated with HD.
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    • Huntington's disease