Our main hypothesis is that the onset of Tourette Syndrome (TS) is dependent on identifiable genetic factors interacting with identifiable environmental factors. We specifically hypothesise that the likelihood of developing tics for children with a family history of TS or another chronic tic disorders is increased by recent exposure to pharyngeal Group A Streptococcus (GAS) carriage or infection, whereby specific GAS types can be identified. The basic hypothesis here is to verify if particular M types are prevalent in children with TS in comparison with a pharyngitis control population and if specific clones, carrying a peculiar repertoire of proteins (superantigens) are associated with the presence of TS. We also hypothesise that development of tics is mediated by identifiable immunological mechanisms in at least a subsample of children, involving both the innate and adaptive immune system. This will be investigated in human studies alongside preclinical studies. Furthermore, we hypothesise that exacerbations in tic severity are associated with consistent patterns of gene expression, in which identifiable environmental factors are involved, most notably GAS carriage or infections of a specific emm type and exposure to psychosocial stress. Finally, we hypothesise that treatment with antibiotics in children with tic disorder with a positive GAS throat culture will lead to reduction in symptom severity.