title: Clustering of dystonia in some pedigrees with autosomal dominant essential tremor suggests the existence of a distinct subtype of essential tremor.
abstract: BACKGROUND
  There is an ongoing debate whether essential tremor (ET) represents a monosymptomatic disorder or other neurologic symptoms are compatible with the diagnosis of ET. Many patients with clinically definite ET develop dystonia. It remains unknown whether tremor associated with dystonia represent a subtype of ET. We hypothesized that ET with dystonia represents a distinct subtype of ET.
  
  
  METHODS
  We studied patients diagnosed with familial ET and dystonia. We included only those patients whose first-degree relatives met diagnostic criteria for ET or dystonia with tremor. This cohort was ascertained for the presence of focal, segmental, multifocal, hemidystonia or generalized dystonia, and ET.
  
  
  RESULTS
  We included 463 patients from 97 kindreds with autosomal dominant mode of inheritance (AD), defined by the vertical transmission of the disease. ET was the predominant phenotype in every ascertained family and each was phenotypically classified as AD ET. "Pure" ET was present in 365 individuals. Focal or segmental dystonia was present in 98 of the 463 patients; 87 of the 98 patients had ET associated with dystonia, one had dystonic tremor and ten had isolated dystonia. The age of onset and tremor severity did not differ between patients with "pure" ET and ET associated with dystonia. We did not observe a random distribution of dystonia in AD ET pedigrees and all patients with dystonia associated with ET were clustered in 28% of all included pedigrees (27/97, p < 0.001).
  
  
  CONCLUSIONS
  Our results suggest that familial ET associated with dystonia may represent a distinct subtype of ET.
authors.affiliation: Department of Neurology, Vanderbilt University, Nashville, TN 37232- 8552, USA. peter.hedera@vanderbilt.edu
authors.forename: Peter
authors.initials: P
authors.lastname: Hedera
authors.forename: Fenna T
authors.initials: FT
authors.lastname: Phibbs
authors.forename: John Y
authors.initials: JY
authors.lastname: Fang
authors.forename: Michael K
authors.initials: MK
authors.lastname: Cooper
authors.forename: P David
authors.initials: PD
authors.lastname: Charles
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Davis
mesh_terms: D000328:Adult; D017668:Age of Onset; D016000:Cluster Analysis; D015331:Cohort Studies; D004198:Disease Susceptibility; D004421:Dystonia / Q000150:complications* / Q000235:genetics; D020329:Essential Tremor / Q000145:classification* / Q000150:complications* / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D012720:Severity of Illness Index; D055815:Young Adult