FAMILIAL ESSENTIAL TREMOR IN 4 KINDREDS - PROSPECTS FOR GENETIC-MAPPING

Objectives: To describe 4 large families with essential tremor (ET) to draw attention to the marked clinical heterogeneity of ET. To use com puter simulation analysis to provide information about the power of th e family material for future linkage studies. Subjects: We examined a total of 251 members from 4 kindreds with ET. The mean (+/-SD) age at onset of ET varied among the 4 kindreds between 19.0+/-11.4 years and 45.6+/-7.4 years. Three of the kindreds had a total of 41 members with the combination of ET and dystonia, typically manifested as torticoll is or dystonic writers' cramp. In 1 of the kindreds, ET seemed to be a ssociated with malignant hyperthermia. One kindred represented ''pure' ' ET without any associated disorders. Methods: In addition to detaile d clinical assessments, we conducted computer simulations on the famil ies' pedigrees using a model that presumed an autosomal dominant inher itance pattern with high penetrance. Results: Although there was evide nce of clinical heterogeneity between the families, the duration of sy mptoms directly correlated with the severity of disease. The computer simulations indicated that 3 of the 4 pedigrees had enough power to ge nerate a significant Linkage result in a total genome search with high ly polymorphic markers. Conclusions: This study confirms the frequent coexistence of ET and dystonia in individual families. Computer simula tions can be used to determine the power of the family to detect a lin ked marker. Identification of the defective gene(s) will enable a bett er understanding and classification of these common movement disorders .