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At a glance

Genetically transmitted progressive neurologic disease characterized by involuntary (choreiform) movements and slowly progressive dementia, leading to death 15 to 20 years after the first clinical symptoms. The symptoms usually begin between 30 and 50 years of age, but can start at any age. It may appear earlier in life with 8% of cases beginning before the age of 20 years. It is often confounded with symptoms more similar to Parkinson’s disease.

Synonyms

Chorea Chronica Progressiva; Chorea Chronica Progressiva Hereditaria; Chorea Hereditaria Chronica; Chorea Progressiva Hereditaria; Chronic Degenerative Chorea; Chorea Major; Erb Vitus Dance; Hereditary Chorea; Huntington Disease (HD); Lund-Huntington Chorea (or Syndrome); Microcellular Striatal Syndrome.

History

Neurodegenerative disorder first described in 1872 by George Huntington of Ohio, US, as a progressive degenerative disorder of the central nervous system associated with involuntary movements and dementia of an unknown etiology. Although this medical condition has been recognized as a disorder since the middle ages, the cause remained unknown until recently. Huntington’s Syndrome was given different names throughout the history as the description of the disease changed. Originally called simply “chorea” for the jerky dance-like movements, HD has also been called “hereditary chorea” and “chronic progressive chorea.” The first definite mention of HD was in a letter by Charles Oscar Waters, published in the first edition of Robley Dunglison’s Practice of Medicine in 1842. Waters described “a form of chorea, vulgarly called magrums,” including accurate descriptions of the chorea, its progression, and the strong heredity of the disease. In 1846, Charles Gorman observed a regional distribution. Johan Christian Lund also produced an early description in 1860. He specifically noted that in Setesdalen, a secluded mountain valley in Norway, there was a high prevalence of dementia associated with a pattern of jerking movement disorders.

Incidence

Prevalence in the general population is estimated at 4 to 7:100,000. No sex or racial predilection. However, localized geographic clusters of disease exist (lowest frequencies have been found in South African blacks, individuals in Japan, and North American blacks).

Genetic inheritance

Autosomal dominant with complete penetrance. New mutations are rare. The HC gene is located on the tip of the long arm of chromosome 4 (locus 4p16.3) and leads to increased length of a CAG triplet repeat at the end of the mRNA. This longer repeat (46 [range 37-86] in Huntington disease v 18 [range 9-37] in normals) leads to unstable gene and gene products. Fully autosomal dominant and homozygotes are no more severely affected than heterozygotes. Juvenile rigid early-onset form is usually paternally inherited.

Pathophysiology

The disease is characterized by premature degeneration of nerve cells. The abnormal protein product (huntingtin) of the HC gene accumulates in selective brain cells in the basal ganglia, particularly the caudate nucleus and putamen, which are severely damaged. ...

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