Screening for mutations in the MECP2 (Rett syndrome) gene in Gilles de la Tourette syndrome

Gilles de la Tourette syndrome (TS) is a relatively common neurobehavioral disorder of childhood onset with a prevalence of 0.7% to 4.2%. Tourette syndrome is characterized by multiple motor and vocal tics, and it is frequently associated with attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, or both. Although studies of families with TS suggest that the disease is inherited as an autosomal trait, the inheritance pattern has not been clearly determined. Using different phenotypic definitions of TS, autosomal dominant, autosomal recessive, and "bilineal" transmission models have been postulated. The dominant model assumes reduced penetrance, and in the bilineal transmission, both parents would have TS or a form fruste of the disease. Effects of additional loci or epigenetic factors may also modify the phenotypic expression. Linkage and sib-pair analyses in families with TS, as well as cytogenetic studies, point to involvement of several autosomal susceptibility loci for TS, including 4q, 7q31, 8p, 11q23, and 18q. X-linked inheritance does not appear to be a major cause of the disease as a high frequency of male-male transmission has been observed. However, the marked predilection of TS for males (male-female ratio of about 4.3:1) has raised the possibility of an X-linked modifier gene affecting the clinical expression of TS.