Finding Genes for Parkinsonism

Abstract

The term parkinsonism refers to a neurological syndrome defined by the combination of bradykinesia (slowness of movement) in combination with any of the following motor signs: tremor at rest, muscular rigidity, and loss of postural reflexes (1). This is an etiologically heterogeneous entity, which might be due to dysfunctions at various levels in the basal ganglia, and especially in the substantia nigra (SN) and striatum. The parkinsonism can be classified into four broad categories: (i) Parkinson's disease (PD, MIM#168600), also called primary parkinsonism, or typical parkinsonism, which includes the common, idiopathic form, and the rare forms with a recently defined genetic etiology; (ii) parkinsonism-plus syndromes, which include different idiopathic, but atypical neurodegenerative forms of parkinsonism (additional motor neurologic features are present); (iii) secondary parkinsonism, which is caused by known, non-genetic etiologies, such as environmental insults (drugs, toxins, viruses), inflammation, tissue infiltration/compression or ischemia; (iv) parkinsonism in the context of other degenerative disorders, with or without a known genetic cause, in which parkinsonism represents a minor, or occasional component of the clinical picture (table 1 ). In the primary forms of parkinsonism (PD) the initial symptoms occur typically in one side of the body, spreading in a few years to the contralateral side. However, a certain degree of clinical asymmetry persists during the more advanced phases of the disease (the body side where the symptoms started remains the more severely affected). Moreover, these motor symptoms display typically a substantial beneficial response to the therapy with levodopa. While the motor symptoms dominate the clinical picture, many PD patients have also other, non-motor problems, such as fatigue, depression, anxiety, sleep disturbances, constipation, bladder and other autonomic disturbances, and sensory complaints (2). The diagnosis of primary parkinsonism (PD) remains based on the presence of the clinical syndrome, and the exclusion of other (secondary) causes.