WESTERN NEBRASKA FAMILY (FAMILY-D) WITH AUTOSOMAL-DOMINANT PARKINSONISM

The etiology of Parkinson's disease (PD) remains uncertain. Environmen tal influences may have an important role, but genetic factors have be en firmly implicated in several recently reported kindreds. We studied a family (family D) whose ancestors probably immigrated to the United States from England. The pedigree contains 188 individuals spanning s ix generations with 18 affected members. Autosomal dominant inheritanc e is present. Typical levo-dopa-responsive PD with bradykinesia, rigid ity, resting tremor, and impaired postural reflexes develops. Eye move ment abnormalities, pyramidal and cerebellar signs, sensory disturbanc es, and orthostatic blood pressure changes do not occur. Disease progr ession is slow. PET with [F-18]-6-fluoro-L-dopa (FD) performed on an a ffected individual revealed decreased uptake of FD in a pattern consis tent with PD. Autopsy performed on another affected individual demonst rated neuronal and pigmentary loss, gliosis, and Lewy bodies in the su bstantia nigra pars compacta. This large kindred appears to represent a neurodegenerative disorder closely resembling, if not identical to, idiopathic PD.