Onset and pre-onset studies to define the Huntington's disease natural history

Huntington's disease's (HD) clinical history has not been defined yet. Howe ver, many aspects of the most confusing clinical stages, i.e., the first an d last disease phases, including the symptom progression and the disease du ration, have been better approached after discovery of the responsible gene . The existence of accurate genetic tests, available for affected and pre-s ymptomatic subjects (i.e., mutation carriers) and the possibility to study transgenic in vivo models, are actually helping us to understand some of th e aspects of HD clinical presentation. HD may present with motor symptoms o ther than chorea, the psychiatric manifestations may represent part of the clinical picture and cognitive deterioration may occur very early in the di sease and depend an early cortical involvement. Pre-onset studies are of cr ucial importance in understanding the temporal sequence of the clinical eve nts. This is also very important for future therapeutic strategies in those diseases initiating late in the life, such as HD. (C) 2001 Elsevier Scienc e Inc.