Huntingtons Disease Chorea

Huntington's disease (HD) is a rare progressive neurological disorder, in which normal central nervous system development is succeeded in early adulthood by premature and selective neuronal death. First-rank symptoms consist of rapid, involuntary jerking movements, or chorea, due to lesions in the putamen and the caudate nucleus, and a progressive dementia due to loss of cells in the cerebral cortex (Hayden 1981). Onset of symptoms is typically in the third or fourth decade, and the clinical course is progressive and relentless over a period of 10 to 30 years. At autopsy, gross examination of HD brains reveals severe, symmetrical atrophy of the frontal and temporal lobes as well as, to a lesser degree, the parietal and occipital lobes. The caudate nucleus is profoundly involved, and diffuse neuronal loss extends into the cerebral cortex, basal ganglia, thalamus, and spinal motor neurons. Various neurotransmitter systems have also been shown to be progressively affected (Rosenberg 1986).

References to the disorder have been found as early as 1841, but the first full description of the disease was made by George S. Huntington in 1872 (Gates 1946). Referring to a large family on Long Island, Huntington distinguished this condition from other known choreiform movement disorders such as Sydenham chorea, or St. Vitus dance. The remarkable history of HD in the New World was recounted in a paper by P. R. Vessie (1932). The carriers of the mutant gene responsible for nearly all known cases of the disease sailed for Massachusetts from Suffolk in 1630. Upon arrival, these individuals founded family lines that included not only the Long Island cases but also the celebrated "Groton witch," whose violent and uncontrollable movements were recorded in 1671 as evidence of possession (Vessie 1932). Compilations of the pedigrees encompassing the various branches of the families founded in seventeenth-century Massachusetts demonstrated a clear pattern of autosomal dominant transmission, meaning that the disease will appear in one-half the offspring of an affected parent.

During the century that has passed since the first description of HD, numerous biochemical and histological studies have been carried out. However, the primary defect in HD remains unknown. A major breakthrough occurred in 1983 when J. F. Gusella and colleagues announced the discovery of an anonymous DNA sequence closely linked to the putative HD gene (Gusella et al. 1983, 1985). This molecular probe, which has been refined by sub-cloning, is now a tool for presymptomatic diagnosis of HD (Folstein et al. 1985). An effort is underway to clone and sequence the HD gene itself in order to determine the precise nature of the pathological changes leading to clinical HD (Gilliam et al. 1987).

Eric J. Devor

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