Familial essential tremor in 4 kindreds. Prospects for genetic mapping
J. Jankovic, J. Beach, M. Pandolfo and P. I. Patel
Department of Neurology, Baylor College of Medicine, Houston, Tex, USA.
OBJECTIVES: 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. 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 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.
