The genetics of the Gilles de la Tourette syndrome: a review.

The Gilles de la Tourette syndrome (GTS) is a hereditary, neuropsychiatric-neurobehavioral disorder with childhood onset that is characterized by motor and vocal tics that may vary from relatively mild to very severe. The exact pathogenesis is still unknown. Following anecdotal reports of familial occurrence, systematic family studies have been carried out since 1980 to establish the mode of inheritance and ultimately to map and clone the susceptibility gene(s). Currently, as a result of combined North American, English, and Dutch studies, the most accepted genetic model is an autosomal dominant pattern of inheritance with incomplete penetrance and a variable expression. The objective of linkage studies is to "link" a particular DNA sequence (with known chromosomal localization) with the disease in all affected family members. Essential for these gene mapping studies is a clear and rigorous definition of the phenotype. Such studies are vastly more difficult if the disease phenotype is ambiguous, proper subject assignment being clouded by incomplete penetrance, cases mild enough to escape detection, or genetically unrelated but highly associated traits. Indeed, because of just these features, the initial optimism about the "well-defined and easy-to-objectivate" phenotype of GTS has gradually been tempered. The tics vary in frequency and severity, are frequently suppressed during examination, or might go unnoticed when associated behavioral symptoms like disturbed impulse control, obsessive-compulsive disorder and attention deficit disorder with hyperkinesia (among others) dominate the clinical picture. Whether these associated behavioral symptoms are a part of the phenotype remains to be established.(ABSTRACT TRUNCATED AT 250 WORDS)