History

George Huntington saw his first cases of HD when he was about 8 years old, while accompanying his father and grandfather on their medical rounds in East Hampton, Long Island. His longitudinal experience with several families of patients, as part of a three-generation family of physicians, was crucial to his famously concise and accurate account of the disease that now bears his name (Huntington, 1872). As William Osler commented in his paper reporting two additional families with HD (Osler, 1893), ‘In the whole range of descriptive nosology there is not, to my knowledge, an instance in which a disease has been so accurately and fully delineated in so few words.’ George Huntington's description over a century ago identified the key aspects of the disease, an adult onset hereditary disorder progressing inexorably to death, and characterized by abnormal movements, as well as cognitive and emotional changes. The pathologic changes in the corpus striatum and cerebral cortex were later described by Meynert, Alzheimer and Hunt in the early part of the twentieth century.

The discovery of the CAG repeat expansion mutation in the gene huntingtin in 1993 greatly facilitated the application of modern molecular and cellular techniques to the study of HD. The consequent development of biochemical, cellular and animal models of the disorder has led to new insights into its pathogenesis. The hope is that these approaches will foster the development of rational therapeutics in the near future.

Clinical course

HD can be described as a triad of motor, cognitive, and emotional disturbances (Folstein, 1989; Harper, 1996; Penney et al., 1990; Ross et al., 1997). Onset is usually insidious, and may occur at any time from childhood to old age, though mid-life onset is most common. Early complaints include clumsiness, difficulty with balance, and jerky movements or tremor. Death occurs an average of 15 to 20 years after the appearance of symptoms, with some patients dying earlier from falls or suicide and others surviving for 30 to 40 years (Fig. 118.1).

The most striking movement disorder of HD consists of abnormal involuntary movements. Chorea or choreoathetosis, continuous and irregular jerky or writhing motions, are the clinical manifestation most frequently associated with Huntington disease. While most commonly present in the limb and trunk, movements may also include motor tics or chorea involving respiratory, laryngeal, pharyngeal, oral or nasal musculature.