Rapid-onset dystonia-parkinsonism: Linkage to chromosome 19q13

Rapid-onset dystonia-parkinsonism (RPD) is an autosomal dominant movement d isorder characterized by sudden onset of persistent dystonia and parkinsoni sm, generally during adolescence or early adulthood. Symptoms evolve over h ours or days, and generally stabilize within a few weeks, with slow or no p rogression. Other features include little or no response to L-dopa, and low levels of homovanillic acid in the central nervous system. Neuroimaging st udies indicate no degeneration of dopaminergic nerve terminals in RDP, sugg esting that this disorder results from a functional deficit, as in dystonia , rather than neuronal loss, as in Parkinson's disease. We studied 81 membe rs of two midwestern US families with RDP, 16 of whom exhibited classic fea tures of RDP. We found significant evidence for linkage in these two famili es to markers on chromosome 19q13, with the highest multipoint LOD score at D19S198 (z = 5.77 at theta = 0.0). The flanking markers D19S587 and D19S90 0 define a candidate region of approximately 8 cM. Although RDP itself is a rare condition, it is important because it has clinical and biochemical si milarities to both Parkinson's disease and dystonia. Identification of the genetic defect in RDP holds promise for understanding the underlying diseas e processes of both of these more common diseases.