A closer look at the history and genetics of Tourette syndrome

Tourette syndrome (TS) was named after Georges Albert Edouard Brutus Gilles de la Tourette, who made its first formal description at the end of the 19 century. Nevertheless, some evidence indicates the disorder may have been recognised at least two thousand years ago. Tic like behaviours were recorded by Aretaeus of Cappadocia and several centuries later by Sprenger and Kraemer, followed by other descriptions. The English writer Samuel Johnson, author of the first English Language Dictionary, showed repetitive body twitches, facial grimaces, barks and grunts, among other tics. He was observed in situations such as going in or out at a door using a certain number of steps, from a certain point, which indicated he had also obsessivecompulsive behaviour. There was some evidence of features of TS as well as co-morbid conditions such as hyperactivity, obsessivecompulsive behaviour or rage attacks in other famous artists and world leaders. Some authors have even proposed that the creative, determined, competitive, and persistent nature of certain people may be related to the presence of TS. Clinicians have observed that some patients are particularly sensitive to the feelings and experiences of others, and more prone to outside stimuli. In this way, empathy could be a common quality in these patients. In 1825, Jean Marc Gaspard Itard made the first known medical description of TS based on two cases, one of which was later followed by Jean-Martin Charcot. In 1885 Gilles de la Tourette put together information from previous fragmented reports and wrote a complete and formal description, thus establishing a novel clinical entity. Behavioural abnormalities such as obsessions, compulsions, inattentiveness and hyperactivity, commonly observed in TS patients, were considered mental tics at the time. Current diagnostic criteria are very similar to Gilles de la Tourette’s description. TS is characterized by the presence of multiple motor and one or more vocal tics. In this disorder, tics are not caused by the direct physiologic effects of a substance or a general medical condition. Tic symptomatology is persistent for over a year, and in this period, tics are not absent for more than three consecutive months. There is no exact consensus between the DSM-IV and the Tourette Syndrome Classification Study Group of whether the age of onset should be prior to 18 or 21 years of age, how cases of onset after 21 years should be diagnosed, and if marked distress or significant impairment caused by tics is necessary to define the condition as definite TS. However, the text revision of the DSM-IV (TR) no longer specifies that TS symptoms have to cause distress or impair the functioning of the patients. With respect to the age of onset, the ICD10 Classification of Mental and Behavioural Disorders describes the onset almost always in childhood or adolescence, and in this way it would no longer exclude cases with later onset. Numerous studies confirmed in the 20 century that genetics plays an important role in the etiology of TS. Family studies proved that the disease runs in families. First-degree relatives of TS patients are indeed in greater risk for TS than the general population. Twin and adoption studies demonstrated that genes have an important role in the etiology of TS, and as much as 90% of the vulnerability to this syndrome could be affected by genes. In addition, environmental, epigenetic and even stochastic factors may affect the susceptibility to TS. At the molecular level, linkage in families and association in unrelated TS subjects have been the main methods used to search for vulnerability genes. Sequencing of almost the entire human genome made it possible to assess the gene expression of thousands of genes on a single chip; recent studies reported a preliminary specific profile in the blood of TS patients. If confirmed, this finding could be useful in the identification of genetic factors related with TS. Given the multi-factorial nature of TS, a thorough clinical description in large samples should be considered; besides association, linkage and sequencing studies, possible gene-gene and geneenvironment interactions would also need to be analysed, as well as epigenetic factors, and gene expression patterns.