Tourette disorder is defined by the combination of persistent motor and phonic tics. These are unwanted, rapid, repetitive and stereotyped movements or vocalizations. The natural history of the disorder includes onset in childhood, a waxing and waning course, and, for many individuals, symptom reduction in adulthood. Current diagnostic approaches dictate that only individuals with the combination of unwanted movements and vocalizations meet criteria for TD. However tics in only one of these domains often occur and, if persistent, are categorized as either chronic motor tics (CMT) or chronic vocal tics (CVT). These are thought to represent a TD spectrum of disorders that also includes the co-occurrence of tics ands obsessive-compulsive disorder (OCD).
TD was once thought to be rare; but estimates now converge on a world -wide prevalence of 0.3–1%, though study samples have tended to be small and many investigations have not met the highest standards for contemporary large scale epidemiological studies[1
]. In addition, despite the observation that as many as 1 percent of the population meets diagnostic criteria for TD, a minority of affected individuals present to clinic with tics as a primary complaint. Moreover, it is typically the coincidence of chronic tics with other psychiatric syndromes, including OCD, depression, and attention deficit hyperactivity disorder that leads individuals and families to seek medical attention. Estimates of comorbidity among TD and these disorders are, accordingly, quite high.
The molecular, cellular and anatomical bases of tics and TD remain in question. However there has been a long-standing consensus regarding the contribution of genetic factors [4
]. From the earliest descriptions of the syndrome, a high degree of heritability has been noted. Indeed, TD was initially thought to represent a single gene, Mendelian disorder [6
]. Presently there is a consensus that overall, TD has a far more complex allelic architecture, one that appears to be similar to other common neuropsychiatric syndromes, involving both a high degree of locus and allelic heterogeneity and polygenic inheritance.
The tentative quality of this description is a consequence of the fact that after a highly productive early era characterizing the heritability and familiality of TD, progress in genetics and genomics over the past decade has been halting. The field is just now beginning to analyze data from what would be considered sufficiently large samples to power reliable studies of common variation and there is, to date, only a single published report of genome wide detection of rare copy number variation (CNV), conducted in a sample of 111 probands and 73 controls [7
]. Indeed when one queries Pubmed for Tourette genetics, fewer than 25 primary research papers are found annually for the last decade. When compared to other complex multi-genic neuropsychiatric syndromes such as autism or schizophrenia, both the differences in the volume of data currently available as well as the rate of growth of the field, based on this crude metric, is striking (). Not surprisingly then, answers to key questions that have begun to be addressed in other areas of psychiatric genetics, regarding the overall contribution of common versus rare variation; the importance of de novo
versus transmitted alleles, and the identity of definitive risk genes are all on the horizon.
Annual publication number in the genetics of Tourette syndrome, autism and schizophrenia
Studies to date have comprehensively and rigorously explored and rejected the hypothesis of single gene inheritance and cumulatively point to limits on the effect sizes of contributing common alleles. Moreover over the last several years rare variant finding have pointed to novel hypotheses regarding pathogenic mechanisms and possibly new avenues for treatment, and recent data suggests the TD may follow a pattern emerging in the study of other neuropsychiatric disorders in which specific sequence or structural variations increase risk for range of outcomes that previously would have been considered distinct.