Clustering of dystonia in some pedigrees with autosomal dominant essential tremor suggests the existence of a distinct subtype of essential tremor

Peter Hedera,John Y Fang,Thomas L Davis,Fenna T Phibbs,Michael K Cooper,P David Charles

doi:10.1186/1471-2377-10-66

Abstract

BackgroundThere 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.MethodsWe 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.ResultsWe 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).ConclusionsOur results suggest that familial ET associated with dystonia may represent a distinct subtype of ET.

Highlights

There is an ongoing debate whether essential tremor (ET) represents a monosymptomatic disorder or other neurologic symptoms are compatible with the diagnosis of ET
Associated with dystonia represents a subtype of ET. It may be a different form of tremor, unrelated to ET, because it has been suggested that postural tremor seen in patients with cervical dystonia has a different pathophysiology than ET [4,5]
Postural and action tremor of the upper extremities was classified into three groups: “pure” or clinically definite ET, where no additional neurological problems were detected; ET associated with dystonia where dystonia did not involve the upper extremities affected by tremor; and dystonic tremor where tremor and dystonia coexisted in the same limb

Summary

Introduction

There is an ongoing debate whether essential tremor (ET) represents a monosymptomatic disorder or other neurologic symptoms are compatible with the diagnosis of ET. There is an ongoing debate whether ET is truly a monosymptomatic disorder because many patients with otherwise typical ET develop dystonia in other body parts that are not affected by tremor [2,3]. It remains unknown whether postural and kinetic tremor associated with dystonia represents a subtype of ET. Cervical dystonia, blepharospasm, and spasmodic dysphonia are commonly observed in patients with postural and kinetic tremor, which is clinically undistinguishable from typical ET [6,7] This tremor needs to be differentiated from dystonic tremor, where dystonic posturing and tremor affect the same body part [8]

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Results

Conclusion