Preface from the Editors

Abstract

Parkinson’s disease (PD) and Huntington’s disease (HD) are the paradigms of opposite movement disorders originating in the basal ganglia. On one hand, poverty and slowness of movement (hypokinesia and bradykinesia) are pathognomic to PD and related conditions. On the other hand, excessive and uncontrolled movements are a hallmark of HD. Indeed, the latter condition is the most common genetic cause of involuntary, fleeting and writhing movements (chorea), which is why the disease used to be called ‘Huntington’s chorea’. Both PD and HD are not only disorders of movement, however. In both conditions, mental processing and mood are affected, and metabolic or autonomic dysfunction cause a range of non-neurological symptoms. From both etiological and epidemiological standpoints, PD and HD appear as two widely different conditions. PD is the second most common neurodegenerative disease after Alzheimer’s and currently affects about 6.3 million people worldwide. It is an age-related disorder lacking an identifiable cause (‘idiopathic’) in 90 % of the cases. By contrast, HD is a relatively rare familial disease caused by an autosomal dominant mutation in the HTT gene. Symptoms of HD commonly become manifest between the ages of 35 and 50 years, but they can begin at virtually any age depending on the CAG repeat length (see below). The genetic basis of HD was discovered in 1993 by an international collaborative effort spearheaded by the Hereditary Disease Foundation. Since then, several other neurological diseases were found to depend on a similar genetic defect, consisting in the expansion of a CAG (cytosine-adenine-guanine) triplet repeat stretch within the disease-causing gene. During the past 17 years, it has become increasingly clear that PD has a strong genetic component, too. Since 1997, several genetic mutations have been positively associated with PD in affected families. Beside these monogenic cases, genetic susceptibility has been suggested to underlie the common idiopathic forms of PD. Indeed, recent genome-wide association studies have established that certain common gene variants occur with an increased frequency in people with idiopathic PD. It is however clear that environmental factors, such as exposure to certain toxins, may underlie many cases of idiopathic PD.