The genetics of Tourette syndrome: A review

O'Rourke, Julia A.; Scharf, Jeremiah M.; Yu, Dongmei; Pauls, David L.

doi:10.1016/j.jpsychores.2009.06.006

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Volume 67, Issue 6 , Pages 533-545, December 2009

The genetics of Tourette syndrome: A review☆

Julia A. O'Rourke
- Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Biomedical Engineering Department, Tufts University, Medford, MA, USA
Jeremiah M. Scharf
- Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
Dongmei Yu
- Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
David L. Pauls
- Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Corresponding author. Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA. Fax: +1 617 726 0830.

Received 19 February 2009; received in revised form 23 June 2009; accepted 26 June 2009. published online 05 October 2009.

Abstract

Objectives

This article 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 significant 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.

Keywords: Tourette's Disorder, Genetics, Family study, Review