Molecular biology of Huntington’s disease

Abstract

Huntington’s disease (HD) is a chronic, degenerative disorder of the central nervous system. It takes its name from George Huntington, a North American physician who first described the characteristic features (Huntington, 1872), which include chorea, generalized impairment of motor function and dementia. The onset of symptoms is usually delayed until the fourth or fifth decade of life, but thereafter the disorder follows a progressive course leading eventually to death after an interval of about 15–20 years. The affected individual initially displays involuntary choreiform movements, and as the disease develops these are accompanied by clumsiness, bradykinesia and the inability to sustain voluntary movement; later in the course of the disease the abnormal movements often give way to a rigid, akinetic state that leaves the patient wheelchair bound or even completely immobile (Folstein, 1989). Although the diagnosis usually depends on the appearance of overt neurological symptoms, these are almost always preceded by subtle psychological abnormalities such as irritability and personality changes, which in some cases can be the most disabling feature of the condition (Hayden, 1981). Associated cognitive difficulties include problems with memory and concentration, difficulty generating problemsolving strategies and profound slowing of mental activity. Anxiety and depression are common features (Folstein et al., 1983a,b) and there is an increased frequency of suicide compared with the general population (Schoenfeld et al., 1984; Farrer, 1986). There is no effective method of treatment at present.