Eapen, Valsamma; (1996) Pathogenesis of Gilles de la Tourette syndrome: Clues from clinical phenotypes. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Gilles de la Tourette Syndrome (GTS) is a developmental neuropsychiatric disorder characterised by multiple motor and vocal tics. More than a century after its original description, there are still controversies about the essential clinical features of GTS, and, the failure as yet to find the putative gene(s) for the disorder may be a reflection of incorrect definition of the phenotypes. In this thesis, genetic data and neuroimaging techniques have been used to elucidate the phenotypic expressions of GTS. A total of 168 First Degree Relatives (FDRs) ascertained through 40 GTS probands and 66 FDRs ascertained through 20 Obsessive Compulsive Disorder (OCD) probands were studied. Findings from the segregation analyses were consistent with an autosomal dominant gene transmission with high penetrance, and sex dependent differences in the expression of GTS. There was also evidence to suggest the existence of a single major gene in the transmission of OCD. A genomic imprinting study of 437 GTS family members showed that maternally transmitted offsprings had a significantly earlier age at onset. There was evidence to suggest that Obsessive Compulsive Behaviour (OCB) forms an alternative phenotypic expression of the putative GTS gene(s). Analysis for GTS and Attention Deficit Hyperactivity Disorder (ADHD) failed to support a similar hypothesis. With regard to tics, it appears that not all cases are genetically related to GTS, and that some may be phenocopies. Single Photon Emission Tomography (SPET) showed that the affected family members of GTS probands had 'hypoperfusion' in the different brain areas. There were no distinctions based on the clinical phenotypes (GTS, Tics or OCB). Phenomenological analysis revealed differences in the obsessive compulsive symptom profile between GTS and OCD probands, but the familial OCD probands shared a similar profile to that of GTS. Implications of these findings in the aetiology and pathogenesis of GTS are discussed.

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