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Tourette syndrome

Author
Joseph Jankovic, MD
Section Editor
Douglas R Nordli, Jr, MD
Deputy Editor
John F Dashe, MD, PhD

INTRODUCTION

Tourette syndrome (TS) is a neurological disorder manifested by motor and phonic tics with onset during childhood [1,2]. This topic will review Tourette syndrome. Other hyperkinetic movement disorders are discussed separately. (See "Hyperkinetic movement disorders in children".)

PATHOGENESIS

TS is thought to result from a complex interaction between social and environmental factors and multiple genetic abnormalities. In most cases a bilineal transmission (inheritance from both parents) is clearly evident [3]. Despite a large number of genetic studies, no single or even multiple causative genes for TS have been identified [4]. The disorder likely results from a disturbance in the striatal-thalamic-cortical (mesolimbic) spinal system, which leads to disinhibition of the motor and limbic system [5].

Although the genetic basis remains elusive, several loci have been identified as candidate susceptibility regions [6]. The discovery of a mutation in the SLITRK1 gene on chromosome 13q31.1 was a major advance in the search for the elusive TS gene or genes [7]. The SLITRK1 gene is expressed in brain regions previously implicated in TS (cortex, hippocampus, thalamic, subthalamic and globus pallidus nuclei, striatum, and cerebellum) and it appears to play a role in dendritic growth. However, it is not clear how the altered gene product leads to the complex neurobehavioral disorder. This mutation appears to be a rare cause of TS as it has not been found in hundreds of TS patients tested.

Another possible rare genetic cause of TS is a mutation in the HDC gene on chromosome 15q21-q22, as detected in two generations of a family with apparent autosomal dominant inheritance of TS [8]. The HDC gene encodes for L-histidine decarboxylase, which is the rate-limiting enzyme that catalyzes the biosynthesis of histamine from histidine. In the central nervous system, histaminergic neurons are located in the posterior hypothalamus but have widespread axonal connections to other brain regions [9]. These findings suggest the possibility of using pharmacologic manipulation of histaminergic neurotransmission to treat TS [8]. However, it is unknown how histamine abnormalities might cause or contribute to TS symptoms.

Neuropathologic examinations have detected no consistent brain abnormalities in patients with TS, but a number of neuroimaging studies have found evidence of structural or metabolic changes in the brain [10]:

                       

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Literature review current through: Nov 2016. | This topic last updated: Tue Aug 30 00:00:00 GMT+00:00 2016.
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