Huntington disease: genetics and epidemiology

Abstract

Huntington disease (HD) is an autosomal dominant disorder in which the major gene expression occurs in the central nervous system. It is characterized by the appearance of progressive chorea and dementia, usually in adult life. One tragic aspect of the disorder, due to its late age of onset and, until recently, lack of a presymptomatic marker, is that transmission of the disease to offspring invariably occurs before symptoms develop in the parent. Although the onset of symptoms and the rate of progression may vary, the prognosis is one of relentless deterioration. The major pathological features of HD are a primary loss of cells in the caudate nucleus and putamen (striatum) but other regions of the basal ganglia, hypothalamus, and brain stem are also involved. Not only is there neuronal loss but there is also a decrease in the level of a number of neurotransmitters and associated enzymes, together with abnormalities in some receptor sites. Martin [1] described the disease as "genetically programmed cell death in the human central nervous system."