Prevalence and features of unreported dystonia in a family study of "pure" essential tremor

Background: Essential tremor (ET) is considered to be a highly heritable disorder, yet no susceptibility genes have been identified. The search for ET genes is severely hampered by clinical and genetic heterogeneity; the existence of this heterogeneity complicates the genetic analyses. We sought to determine the prevalence and clinical features of unreported dystonia in a family study of " pure" ET. Methods: ET probands and their reportedly affected first-and second-degree relatives were enrolled in a genetics study, the Family Study of Essential Tremor (FASET) at Columbia University Medical Center. The goal was to enroll cases with " pure" ET (i.e., ET without dystonia or other neurological problems). Each enrollee underwent a detailed neurological evaluation. Results: There were 100 enrollees (28 probands, 72 relatives). Dystonia (primarily torticollis) occurred in 9 (32.1%) of 28 families, with 5 cases in one family, 2 cases in two families, and 1 case in six families. Those affected with dystonia included 3 (10.7%) probands and 12 (16.7%) relatives. There was a gender predilection: 14/15 (93.3%) with dystonia vs. 41/85 (48.2%) without dystonia were women (p = 0.001). Dystonia was previously undiagnosed in 14/15 (93.3%) cases. Conclusions: Dystonia (esp. torticollis in women) was present in nearly one-third of the ET families in a genetics study, including 10.7% of ET probands. Dystonia was unreported and previously undiagnosed in nearly all of these individuals. The overarching biological issue is whether ET and dystonia should be regarded as one disease or two; this has obvious implications for the structuring of analyses in genetic studies.