The genetics of Tourette syndrome: A review

Abstract

Objectives-This paper summarizes and evaluates recent advances in the genetics of Gilles de la Tourette Syndrome (GTS).Methods-This is a review of recent literature focusing on: 1) the genetic etiology of GTS; 2) common genetic components of GTS, Attention Deficit Hyperactivity Disorder (ADHD), and Obsessive Compulsive Disorder (OCD); 3) recent linkage studies of GTS; 4) chromosomal translocations in GTS; and 5) candidate gene studies.Results-Family, twin and segregation studies provide strong evidence for the genetic nature of GTS. GTS is a heterogeneous disorder with complex inheritance patterns and phenotypic manifestations. Family studies of GTS and OCD indicate that an early onset form of OCD is likely to share common genetic factors with GTS. While there apparently is an etiological relationship between GTS and ADHD, it appears that the common form of ADHD does not share genetic factors with GTS. The largest genome wide linkage study to date observed evidence for linkage on chromosome 2p23.2 (P=3.8 × 10 −5 ). No causative candidate genes have been identified, and recent studies suggest that the newly identified candidate gene SLITRK1 is not a major risk gene for the majority of individuals with GTS. Conclusion-The genetics of GTS are complex and not well understood. The Genome Wide Association Study (GWAS) design can hopefully overcome the limitations of linkage and candidate gene studies. However, large-scale collaborations are needed to provide enough power to utilize the GWAS design for discovery of causative mutations. Knowledge of susceptibility mutations and biological pathways involved should eventually lead to new treatment paradigms for GTS. KeywordsTourette's Disorder; Genetics; Family study; ReviewIn the original description of the syndrome that bears his name, Georges Gilles de la Tourette observed that the disorder was familial [1]. Subsequently, there has been considerable research devoted to systematically examining whether that original observation could be replicated and whether the observed familiality is due in part to genetic factors. These studies have included family studies, twin studies, genetic linkage studies and genetic association (candidate gene)Correspondence to: Dr. David L. Pauls, PNGU, 185 Cambridge Street, Massachusetts General Hospital, Boston, MA 02114; dpauls@pngu.mgh.harvard.edu; fax: (617)726-0830. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Family StudiesFamily studies have repeatedly demonstrated that Gilles de la Tourette Syndrome (GTS) is highly familial. Establishing that there is familial ag...

Neurobiology of Tourette Syndrome: Current Status and Need for Further Investigation: Table 1.

“…Despite these reports, the precise pattern of transmission and the specific genes involved remain elusive. Linkage analyses have suggested several chromosomal locations, but without a clear reproducible locus (Pauls, 2006;O'Rourke et al, 2009). Similarly, candidate gene studies have failed to yield consistent results for specific susceptibility genes.…”

Tourette Syndrome: A Case Report, When Exclusion of Differential Diagnoses and Comorbidities Really Matters

“…The definitive etiology of TS is unknown but there is a universal agreement about the strong genetic vulnerability for the disorder with some environmental factors that may play a role in the expression of its severity [9]. The reported case was the first born to a first cousin consanguineous parents (paterno-paternal), nevertheless there were no similar cases in his family or an exposure to a predisposing environmental factor before the development of TS symptomatology.…”

Tourette Syndrome; Is It an Annoying Disorder or an Inspiring Companion??!!!

“…Some TS cases were reported to act like those suffering from autosomal dominant disorders with 50% chance to transmit the mutant gene(s) to their offspring but whether the mutant gene(s) will be expressed or not and to what extent and form is greatly variable (variable expression and incomplete penetrance). In addition, it was found that gender plays a role in gene expression in cases of TS as males are more likely to manifest tics than females [14,15].…”