In 1872, George Huntington described a unique ailment involving characteristic involuntary movements that begin insidiously, usually in middle age, and progress gradually until the victim is consumed by full-blown chorea.1 His description was based on his observations of families with the disorder in his clinical practice as a family physician in East Hampton, on Long Island, New York. As members of the same families had been cared for by his father and grandfather, who were also physicians, Huntington was attuned to the inherited nature of the peculiar disorder. He described frequent transmission of the defect from either an affected mother or an affected father to offspring, with no skipping of generations. Huntington also noted that “if by any chance these children go through life without it, the thread is broken and the children and great grandchildren of the original shakers may rest assured that they are free from the disease.” This pattern of transmission was recognized as the result of a mendelian autosomal-dominant defect by Osler in 1908.2 Indeed, Vessie3 later traced many of the Long Island families to immigrants from Bures, England, who landed in New England in 1649, confirming Huntington's description of this hereditary chorea as “an heirloom from generations away back in the dim past.” George Huntington's accurate, lucid, and succinct description of this nightmarish affliction led to its appellation of Huntington's chorea, subsequently changed to Huntington's disease (HD), as its manifestations are not limited to loss of motor control.
Although Huntington believed that the disorder existed only in eastern Long Island, it is now known to be widespread throughout the world. The prevalence is highest in populations of western European ancestry, in which 4–7 persons/100,000 are affected.4 However, the actual disease gene frequency is 2.5–3 times higher, as HD typically has its onset only in midlife, and, at any given time, two thirds of gene carriers have yet to become symptomatic. The prevalence is relatively consistent across Europe and in other regions of the world that have populations of western European descent, with the exception of Finland, where a significantly lower rate reflects this population's restricted genetic origin. HD is also seen in Africans and Asians, although with a much lower prevalence.
Many of the early studies of HD concentrated on its familial nature, documenting large kindreds in which the defect was passed from generation to generation. HD, as an autosomal-dominant disorder, is transmitted equally from males and females, and both sexes have a 50:50 chance of inheriting the defect. The disease gene is highly penetrant, but onset is variable, ranging from early childhood to late in life. As most cases manifest in middle age, the HD gene is often passed on to children before the parent is aware of the disorder. The rare cases of juvenile onset (<15 years of age) are usually inherited from an affected father.5,6
HD is currently untreatable, except for palliative care, and its victims are condemned to slow, inexorable progression of ...