title: Familial essential tremor in 4 kindreds. Prospects for genetic mapping.
abstract: OBJECTIVE
  To describe 4 large families with essential tremor (ET) to draw attention to the marked clinical heterogeneity of ET. To use computer simulation analysis to provide information about the power of the family material for future linkage studies.
  
  
  METHODS
  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 torticollis or dystonic writers' cramp. In 1 of the kindreds, ET seemed to be associated with malignant hyperthermia. One kindred represented "pure" ET without any associated disorders.
  
  
  METHODS
  In addition to detailed clinical assessments, we conducted computer simulations on the families' pedigrees using a model that presumed an autosomal dominant inheritance pattern with high penetrance.
  
  
  RESULTS
  Although there was evidence of clinical heterogeneity between the families, the duration of symptoms directly correlated with the severity of disease. The computer simulations indicated that 3 of the 4 pedigrees had enough power to generate a significant linkage result in a total genome search with highly polymorphic markers.
  
  
  CONCLUSIONS
  This study confirms the frequent coexistence of ET and dystonia in individual families. Computer simulations can be used to determine the power of the family to detect a linked marker. Identification of the defective gene(s) will enable a better understanding and classification of these common movement disorders.
authors.affiliation: Department of Neurology, Baylor College of Medicine, Houston, Tex, USA.
authors.forename: J
authors.initials: J
authors.lastname: Jankovic
authors.forename: J
authors.initials: J
authors.lastname: Beach
authors.forename: M
authors.initials: M
authors.lastname: Pandolfo
authors.forename: P I
authors.initials: PI
authors.lastname: Patel
mesh_terms: D000368:Aged; D004421:Dystonia / Q000150:complications; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D010300:Parkinson Disease / Q000150:complications; D010375:Pedigree; D014202:Tremor / Q000150:complications / Q000235:genetics*