Gilles de la Tourette syndrome

Article metrics

Abstract

Gilles de la Tourette syndrome (GTS) is a childhood-onset neurodevelopmental disorder that is characterized by several motor and phonic tics. Tics usually develop before 10 years of age, exhibit a waxing and waning course and typically improve with increasing age. A prevalence of approximately 1% is estimated in children and adolescents. The condition can result in considerable social stigma and poor quality of life, especially when tics are severe (for example, with coprolalia (swearing tics) and self-injurious behaviours) or when GTS is accompanied by attention-deficit/hyperactivity disorder, obsessive–compulsive disorder or another neuropsychiatric disorder. The aetiology is complex and multifactorial. GTS is considered to be polygenic, involving multiple common risk variants combined with rare, inherited or de novo mutations. These as well as non-genetic factors (such as perinatal events and immunological factors) are likely to contribute to the heterogeneity of the clinical phenotype, the structural and functional brain anomalies and the neural circuitry involvement. Management usually includes psychoeducation and reassurance, behavioural methods, pharmacotherapy and, rarely, functional neurosurgery. Future research that integrates clinical and neurobiological data, including neuroimaging and genetics, is expected to reveal the pathogenesis of GTS at the neural circuit level, which may lead to targeted interventions.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: Key events in the history of Gilles de la Tourette syndrome.
Figure 2: Course of tic severity in Gilles de la Tourette syndrome.
Figure 3: Genetic architecture of Gilles de la Tourette syndrome and related developmental tic disorders.
Figure 4: CSTC circuit.
Figure 5: Decision tree for the management of Gilles de la Tourette syndrome.
Figure 6: Stylized depiction of quality-of-life domains affected in Gilles de la Tourette syndrome.

References

  1. 1

    Robertson, M. M. A personal 35 year perspective on Gilles de la Tourette syndrome: prevalence, phenomenology, comorbidities, and coexistent psychopathologies. Lancet Psychiatry 2, 68–87 (2015). This two-part review gives a personal perspective of managing patients with GTS over a period of 35 years, and then compares this to updated evidence as it relates to prevalence, phenomenology, comorbidities and coexistent psychopathologies.

  2. 2

    American Psychatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (American Psychiatric Association, 2013).

  3. 3

    Altshuler, L. L. et al. Who seeks mental health care in China? Diagnoses of Chinese outpatients according to DSM-III criteria and the Chinese classification system. Am. J. Psychiatry 145, 872–875 (1988).

  4. 4

    Ming-Yuan, Z. The diagnosis and phenomenology of neurasthenia a Shanghai study. Cult. Med. Psychiatry 13, 147–161 (1989).

  5. 5

    Eapen, V. & Robertson, M. M. Are there distinct subtypes in Tourette syndrome? Pure-Tourette syndrome versus Tourette syndrome-plus, and simple versus complex tics. Neuropsychiatr. Dis. Treat. 11, 1431–1436 (2015). This paper provides crucial insights into the similarities and differences between patients presenting with only motor and vocal tics compared with those also exhibiting associated comorbidities and psychopathologies.

  6. 6

    Eapen, V. & Črnčec, R. DSM 5 and child psychiatric disorders: what is new? What has changed? Asian J. Psychiatr. 11, 114–118 (2014).

  7. 7

    Eapen, V., Pauls, D. L. & Robertson, M. M. Evidence for autosomal dominant transmission in Tourette's syndrome. United Kingdom cohort study. Br. J. Psychiatry 162, 593–596 (1993).

  8. 8

    Caprini, G. & Melotti, V. Un grave sindrome ticcosa guarita con haloperidol. Riv. Sper. Freniatr. 85, 191–196 (1961).

  9. 9

    Seignot, J. A case of tic of Gilles de la Tourette cured by R 1625. Ann. Med. Psychol. 119, 578–579 (1961).

  10. 10

    Robertson, M. M. Tourette syndrome, associated conditions and the complexities of treatment. Brain 3, 425–462 (2000).

  11. 11

    Roessner, V. et al. European clinical guidelines for Tourette syndrome and other tic disorders. Part II: pharmacological treatment. Eur. Child Adolesc. Psychiatry 20, 173–196 (2011). These are the first consensus guidelines on the treatment of tic disorders and GTS, including a definition of treatment indication.

  12. 12

    Thenganatt, M. A. & Jankovic, J. Recent advances in understanding and managing Tourette syndrome. F1000Res. 5 (F1000 Faculty Rev), 152 (2016).

  13. 13

    Comings, D. E., Himes, J. A. & Comings, B. G. An epidemiologic study of Tourette's syndrome in a single school district. J. Clin. Psychiatry 51, 463–469 (1990).

  14. 14

    Jankovic, J. & Kurlan, R. Tourette syndrome: evolving concepts. Mov. Disord. 26, 1149–1156 (2011).

  15. 15

    Scahill, L., Dalsgaard, S. & Bradbury, K. in Tourette Syndrome (eds Martino, D. & Leckman, J. F. ) 121–133 (Oxford Univ. Press, 2013).

  16. 16

    Centers for Disease Control & Prevention. Prevalence of diagnosed Tourette syndrome in persons aged 6–17 years — United States, 2007. MMWR Morb. Mortal. Wkly Rep. 58, 581–585 (2009).

  17. 17

    Robertson, M. M. The prevalence and epidemiology of Gilles de la Tourette syndrome. Part 1: the epidemiological and prevalence studies. J. Psychosom. Res. 65, 461–472 (2008).

  18. 18

    Knight, T. et al. Prevalence of tic disorders: a systematic review and meta-analysis. Pediatr. Neurol. 47, 77–90 (2012). This meta-analysis has helped to clarify the variations in prevalence rates of GTS and provides directions for future epidemiological studies.

  19. 19

    Scharf, J. M. et al. Population prevalence of Tourette syndrome: a systematic review and meta-analysis. Mov. Disord. 30, 221–228 (2015).

  20. 20

    Steinberg, T., Tamir, I., Zimmerman-Brenner, S., Friling, M. & Apter, A. Prevalence and comorbidity of tic disorder in Israeli adolescents: results from a national mental health survey. Isr. Med. Assoc. J. 15, 94–98 (2013).

  21. 21

    Chinese Society of Psychiatry. The Chinese Classification and Diagnostic Criteria of Mental Disorders Version 3 (CCMD-3) (Chinese Society of Psychiatry, 2001).

  22. 22

    Jin, R. et al. Epidemiological survey of Tourette syndrome in children and adolescents in Wenzhou of PR China. Eur. J. Epidemiol. 20, 925–927 (2005).

  23. 23

    Wang, H.-S. & Kuo, M.-F. Tourette's syndrome in Taiwan: an epidemiological study of tic disorders in an elementary school at Taipei County. Brain Dev. 25, S29–S31 (2003).

  24. 24

    Atladóttir, H. O. et al. Time trends in reported diagnoses of childhood neuropsychiatric disorders: a Danish cohort study. Arch. Pediatr. Adolesc. Med. 161, 193–198 (2007).

  25. 25

    Leivonen, S. et al. A nationwide register study of the characteristics, incidence and validity of diagnosed Tourette syndrome and other tic disorders. Acta Paediatr. 103, 984–990 (2014).

  26. 26

    Pauls, D. L., Fernandez, T. V., Mathews, C. A., State, M. W. & Scharf, J. M. The inheritance of Tourette disorder: a review. J. Obsessive Compuls. Relat. Disord. 3, 380–385 (2014).

  27. 27

    Browne, H. A. et al. Familial clustering of tic disorders and obsessive–compulsive disorder. JAMA Psychiatry 72, 359–366 (2015).

  28. 28

    Mataix-Cols, D. et al. Familial risks of Tourette syndrome and chronic tic disorders. A population-based cohort study. JAMA Psychiatry 72, 787–793 (2015).

  29. 29

    Paschou, P. The genetic basis of Gilles de la Tourette syndrome. Neurosci. Biobehav. Rev. 37, 1026–1039 (2013).

  30. 30

    Georgitsi, M. et al. The genetic etiology of Tourette syndrome: large-scale collaborative efforts on the precipice of discovery. Front. Neurosci. 10, 351 (2016).

  31. 31

    Davis, L. K. et al. Partitioning the heritability of Tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture. PLoS Genet. 9, e1003864 (2013). This landmark study uses multivariate modelling to provide the first direct genetic measure of aggregated GTS genetic risk (that is, heritability) captured by genome-wide association studies and demonstrates that GTS is predominantly a polygenic disorder, with risk variants distributed widely across the genome that overlap significantly with, but are also distinct from, OCD genetic risk.

  32. 32

    Cross-Disorder Group of the Psychiatric Genomics Consortium. Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet 381, 1371–1379 (2013).

  33. 33

    Cross-Disorder Group of the Psychiatric Genomics Consortium. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nat. Genet. 45, 984–994 (2013).

  34. 34

    Abelson, J. F. et al. Sequence variants in SLITRK1 are associated with Tourette's syndrome. Science 310, 317–320 (2005).

  35. 35

    Scharf, J. M. et al. Lack of association between SLITRK1var321 and Tourette syndrome in a large family-based sample. Neurology 70, 1495–1496 (2008).

  36. 36

    Miranda, D. M. et al. Association of SLITRK1 to Gilles de la Tourette syndrome. Am. J. Med. Genet. B Neuropsychiatr. Genet. 150B, 483–486 (2009).

  37. 37

    O’Roak, B. J. et al. Additional support for the association of SLITRK1 var321 and Tourette syndrome. Mol. Psychiatry 15, 447–450 (2010).

  38. 38

    Karagiannidis, I. et al. Replication of association between a SLITRK1 haplotype and Tourette syndrome in a large sample of families. Mol. Psychiatry 17, 665–668 (2012).

  39. 39

    Ercan-Sencicek, A. G. et al. L-Histidine decarboxylase and Tourette's syndrome. N. Engl. J. Med. 362, 1901–1908 (2010).

  40. 40

    Fernandez, T. V. et al. Rare copy number variants in Tourette syndrome disrupt genes in histaminergic pathways and overlap with autism. Biol. Psychiatry 71, 392–402 (2011).

  41. 41

    Karagiannidis, I. et al. Support of the histaminergic hypothesis in Tourette syndrome: association of the histamine decarboxylase gene in a large sample of families. J. Med. Genet. 50, 760–764 (2013).

  42. 42

    Scharf, J. M. et al. Genome-wide association study of Tourette's syndrome. Mol. Psychiatry 18, 721–728 (2013).

  43. 43

    Paschou, P. et al. Genetic association signal near NTN4 in Tourette syndrome. Ann. Neurol. 76, 310–315 (2014).

  44. 44

    Huang, A. Y. et al. Rare copy number variants in NRXN1 and CNTN6 increase risk for Tourette syndrome. Preprint at bioRxivhttp://dx.doi.org/10.1101/062471 (2016).

  45. 45

    Sundaram, S. K., Huq, A. M., Wilson, B. J. & Chugani, H. T. Tourette syndrome is associated with recurrent exonic copy number variants. Neurology 74, 1583–1590 (2010).

  46. 46

    Nag, A. et al. CNV analysis in Tourette syndrome implicates large genomic rearrangements in COL8A1 and NRXN1. PLoS ONE 8, e59061 (2013).

  47. 47

    Bertelsen, B. et al. Association of AADAC deletion and Gilles de la Tourette syndrome in a large European cohort. Biol. Psychiatry 79, 383–391 (2016).

  48. 48

    Hirschtritt, M. E. et al. Lifetime prevalence, age of risk, and genetic relationships of comorbid psychiatric disorders in Tourette syndrome. JAMA Psychiatry 72, 325–333 (2015).

  49. 49

    Huisman-van Dijk, H. M., Schoot, R., Rijkeboer, M. M., Mathews, C. A. & Cath, D. C. The relationship between tics, OC, ADHD and autism symptoms: a cross-disorder symptom analysis in Gilles de la Tourette syndrome patients and family-members. Psychiatry Res. 237, 138–146 (2016).

  50. 50

    Mathews, C. A. & Grados, M. A. Familiality of Tourette syndrome, obsessive–compulsive disorder, and attention-deficit/hyperactivity disorder: heritability analysis in a large sib-pair sample. J. Am. Acad. Child Adolesc. Psychiatry 50, 46–54 (2011).

  51. 51

    Karagiannidis, I. et al. The genetics of Gilles de la Tourette syndrome: a common aetiological basis with comorbid disorders? Curr. Behav. Neurosci. Rep. 3, 218–231 (2016).

  52. 52

    McGrath, L. M. et al. Copy number variation in obsessive–compulsive disorder and tourette syndrome: a cross-disorder study. J. Am. Acad. Child Adolesc. Psychiatry 53, 910–919 (2014).

  53. 53

    Zilhao, N. R. et al. Epigenome-wide association study of tic disorders. Twin Res. Hum. Genet. 18, 699–709 (2015).

  54. 54

    Clarke, R., Lee, S. & Eapen, V. Pathogenetic model for Tourette syndrome delineates overlap with related neurodevelopmental disorders including Autism. Transl Psychiatry 2, e158 (2012).

  55. 55

    Yu, D. et al. Cross-disorder genome-wide analyses suggest a complex genetic relationship between Tourette's syndrome and OCD. Am. J. Psychiatry 172, 82–93 (2015).

  56. 56

    Anttila, V. et al. Analysis of shared heritability in common disorders of the brain. Preprint at bioRxivhttp://dx.doi.org/10.1101/048991 (2016).

  57. 57

    Barabas, G., Matthews, W. S. & Ferrari, M. Tourette's syndrome and migraine. Arch. Neurol. 41, 871–872 (1984).

  58. 58

    Tsetsos, F. et al. Meta-analysis of Tourette syndrome and attention deficit hyperactivity disorder provides support for a shared genetic basis. Front. Neurosci. 10, 340 (2016).

  59. 59

    Anttila, V. et al. Genome-wide meta-analysis identifies new susceptibility loci for migraine. Nat. Genet. 45, 912–917 (2013).

  60. 60

    Bergink, V., Gibney, S. M. & Drexhage, H. A. Autoimmunity, inflammation, and psychosis: a search for peripheral markers. Biol. Psychiatry 75, 324–331 (2014).

  61. 61

    Chao, T.-K., Hu, J. & Pringsheim, T. Prenatal risk factors for Tourette syndrome: a systematic review. BMC Pregnancy Childbirth 14, 1 (2014).

  62. 62

    Hoekstra, P. J., Dietrich, A., Edwards, M. J., Elamin, I. & Martino, D. Environmental factors in Tourette syndrome. Neurosci. Biobehav. Rev. 37, 1040–1049 (2013).

  63. 63

    Martino, D., Zis, P. & Buttiglione, M. The role of immune mechanisms in Tourette syndrome. Brain Res. 1617, 126–143 (2015).

  64. 64

    Lin, H. et al. Streptococcal upper respiratory tract infections and psychosocial stress predict future tic and obsessive–compulsive symptom severity in children and adolescents with Tourette syndrome and obsessive–compulsive disorder. Biol. Psychiatry 67, 684–691 (2010).

  65. 65

    Israelashvili, M. & Bar-Gad, I. Corticostriatal divergent function in determining the temporal and spatial properties of motor tics. J. Neurosci. 35, 16340–16351 (2015).

  66. 66

    Dalsgaard, S., Waltoft, B. L., Leckman, J. F. & Mortensen, P. B. Maternal history of autoimmune disease and later development of Tourette syndrome in offspring. J. Am. Acad. Child Adolesc. Psychiatry 54, 495–501.e1 (2015).

  67. 67

    Chang, Y.-T. et al. Correlation of Tourette syndrome and allergic disease: nationwide population-based case–control study J. Dev. Behav. Pediatr. 32, 98–102 (2011).

  68. 68

    Lennington, J. B. et al. Transcriptome analysis of the human striatum in Tourette syndrome. Biol. Psychiatry 79, 372–382 (2016). This is the first analysis of the striatal transcriptome of post-mortem brains of patients with GTS, which supports a key role for GABAergic and cholinergic interneurons and microglia in the pathogenesis of GTS.

  69. 69

    Kumar, A., Williams, M. T. & Chugani, H. T. Evaluation of basal ganglia and thalamic inflammation in children with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection and Tourette syndrome a positron emission tomographic (PET) study using C-[R]-PK11195. J. Child Neurol. 30, 749–756 (2015).

  70. 70

    Lit, L., Enstrom, A., Sharp, F. R. & Gilbert, D. L. Age-related gene expression in Tourette syndrome. J. Psychiatr. Res. 43, 319–330 (2009).

  71. 71

    Gunther, J. et al. Catecholamine-related gene expression in blood correlates with tic severity in Tourette syndrome. Psychiatry Res. 200, 593–601 (2012).

  72. 72

    Tian, Y. et al. GABA- and acetylcholine-related gene expression in blood correlate with tic severity and microarray evidence for alternative splicing in Tourette syndrome: a pilot study. Brain Res. 1381, 228–236 (2011).

  73. 73

    Wenzel, C., Wurster, U. & Müller-Vahl, K. R. Oligoclonal bands in cerebrospinal fluid in patients with Tourette's syndrome. Mov. Disord. 26, 343–346 (2011).

  74. 74

    Delorme, C. et al. Enhanced habit formation in Gilles de la Tourette syndrome. Brain 139, 605–615 (2016).

  75. 75

    Singer, H. S. Motor control, habits, complex motor stereotypies, and Tourette syndrome. Ann. NY Acad. Sci. 1304, 22–31 (2013).

  76. 76

    Singer, H. S. Habitual and goal-directed behaviours and Tourette syndrome. Brain 139, 312–316 (2016).

  77. 77

    Crittenden, J. R. & Graybiel, A. M. Basal ganglia disorders associated with imbalances in the striatal striosome and matrix compartments. Front. Neuroanat. 5, 59 (2011).

  78. 78

    Singer, H. S. in Tourette Syndrome(eds Martino, D. & Leckman, J. F. ) 276–300 (Oxford Univ. Press, 2013).

  79. 79

    Singer, H. S., Puts, N., Tochen, L., Edden, R. A. E. & Mahone, E. M. GABA and glutamate in children with Tourette syndrome: a 7T study. Ann. Neurol. 80, S292–S293 (2016).

  80. 80

    Pogorelov, V., Xu, M., Smith, H. R., Buchanan, G. F. & Pittenger, C. Corticostriatal interactions in the generation of tic-like behaviors after local striatal disinhibition. Exp. Neurol. 265, 122–128 (2015).

  81. 81

    Gilbert, D. L. et al. Association of cortical disinhibition with tic, ADHD, and OCD severity in Tourette syndrome. Mov. Disord. 19, 416–425 (2004).

  82. 82

    Puts, N. A. et al. Reduced GABAergic inhibition and abnormal sensory symptoms in children with Tourette syndrome. J. Neurophysiol. 114, 808–817 (2015).

  83. 83

    Draper, A. et al. Increased GABA contributes to enhanced control over motor excitability in Tourette syndrome. Curr. Biol. 24, 2343–2347 (2014).

  84. 84

    Bronfeld, M., Yael, D., Belelovsky, K. & Bar-Gad, I. Motor tics evoked by striatal disinhibition in the rat. Front. Syst. Neurosci. 7, 50 (2013).

  85. 85

    Xu, M. et al. Targeted ablation of cholinergic interneurons in the dorsolateral striatum produces behavioral manifestations of Tourette syndrome. Proc. Natl Acad. Sci. USA 112, 893–898 (2015).

  86. 86

    Nelson, A. B. et al. Striatal cholinergic interneurons drive GABA release from dopamine terminals. Neuron 82, 63–70 (2014).

  87. 87

    Wong, D. F. et al. Mechanisms of dopaminergic and serotonergic neurotransmission in Tourette syndrome: clues from an in vivo neurochemistry study with PET. Neuropsychopharmacology 33, 1239–1251 (2008).

  88. 88

    Baldan, L. C. et al. Histidine decarboxylase deficiency causes tourette syndrome: parallel findings in humans and mice. Neuron 81, 77–90 (2014).

  89. 89

    Rapanelli, M. et al. Dysregulated intracellular signaling in the striatum in a pathophysiologically grounded model of Tourette syndrome. Eur. Neuropsychopharmacol. 24, 1896–1906 (2014).

  90. 90

    Befort, K. Interactions of the opioid and cannabinoid systems in reward: insights from knockout studies. Front. Pharmacol. 6, 6 (2015).

  91. 91

    Massotte, D. Monitoring endogenous GPCRs: lessons for drug design. Front. Pharmacol. 6, 146 (2015).

  92. 92

    Whiting, P. F. et al. Cannabinoids for medical use: a systematic review and meta-analysis. JAMA 313, 2456–2473 (2015).

  93. 93

    Robertson, M. M. A personal 35 year perspective on Gilles de la Tourette syndrome: assessment, investigations, and management. Lancet Psychiatry 2, 88–104 (2015).

  94. 94

    Moriarty, J. et al. HMPAO SPET does not distinguish obsessive–compulsive and tic syndromes in families multiply affected with Gilles de la Tourette's syndrome. Psychol. Med. 27, 737–740 (1997).

  95. 95

    Muellner, J. et al. Altered structure of cortical sulci in Gilles de la Tourette syndrome: further support for abnormal brain development. Mov. Disord. 30, 655–661 (2015).

  96. 96

    Bloch, M. H., Leckman, J. F., Zhu, H. & Peterson, B. S. Caudate volumes in childhood predict symptom severity in adults with Tourette syndrome. Neurology 65, 1253–1258 (2005).

  97. 97

    Leckman, J. F., Bloch, M. H., Sukhodolsky, D. G., Scahill, L. & King, R. A. in Tourette Syndrome(eds Martino, D. & Leckman, J. F. ) 3–25 (Oxford Univ. Press, 2013).

  98. 98

    Peterson, B. S. & Leckman, J. F. The temporal dynamics of tics in Gilles de la Tourette syndrome. Biol. Psychiatry 44, 1337–1348 (1998).

  99. 99

    Jankovic, J. & Stone, L. Dystonic tics in patients with Tourette's syndrome. Mov. Disord. 6, 248–252 (1991).

  100. 100

    Robertson, M. M., Trimble, M. R. & Lees, A. The psychopathology of the Gilles de la Tourette syndrome. A phenomenological analysis. Br. J. Psychiatry 152, 383–390 (1988).

  101. 101

    Freeman, R. D. et al. An international perspective on Tourette syndrome: selected findings from 3500 individuals in 22 countries. Dev. Med. Child Neurol. 42, 436–447 (2000).

  102. 102

    Freeman, R. D. et al. Coprophenomena in Tourette syndrome. Dev. Med. Child Neurol. 51, 218–227 (2009).

  103. 103

    Robertson, M. M. & Gourdie, A. Familial Tourette's syndrome in a large British pedigree. Associated psychopathology, severity, and potential for linkage analysis. Br. J. Psychiatry 156, 515–521 (1990).

  104. 104

    Eapen, V. & Robertson, M. M. Gilles de la Tourette syndrome in Malta: psychopathology in a multiply affected pedigree. Arab J. Psychiatry 6, 113–118 (1995).

  105. 105

    Eapen, V., Robertson, M. M., Zeitlin, H. & Kurlan, R. Gilles de la Tourette's syndrome in special education schools: a United Kingdom study. J. Neurol. 244, 378–382 (1997).

  106. 106

    Baron-Cohen, S., Scahill, V. L., Izaguirre, J., Hornsey, H. & Robertson, M. M. The prevalence of Gilles de la Tourette syndrome in children and adolescents with autism: a large scale study. Psychol. Med. 29, 1151–1159 (1999).

  107. 107

    Baron-Cohen, S., Mortimore, C., Moriarty, J., Izaguirre, J. & Robertson, M. M. The prevalence of Gilles de la Tourette's syndrome in children and adolescents with autism. J. Child Psychol. Psychiatry 40, 213–218 (1999).

  108. 108

    Hornsey, H., Banerjee, S., Zeitlin, H. & Robertson, M. M. The prevalence of Tourette syndrome in 13–14-year-olds in mainstream schools. J. Child Psychol. Psychiatry 42, 1035–1039 (2001).

  109. 109

    Lin, H. et al. Psychosocial stress predicts future symptom severities in children and adolescents with Tourette syndrome and/or obsessive–compulsive disorder. J. Child Psychol. Psychiatry 48, 157–166 (2007).

  110. 110

    Scahill, L. et al. Thermal sensitivity in Tourette syndrome: preliminary report. Percept. Mot. Skills 92, 419–432 (2001).

  111. 111

    Cheung, M. Y. C., Shahed, J. & Jankovic, J. Malignant Tourette syndrome. Mov. Disord. 22, 1743–1750 (2007).

  112. 112

    Robertson, M. M., Trimble, M. & Lees, A. Self-injurious behaviour and the Gilles de la Tourette syndrome: a clinical study and review of the literature. Psychol. Med. 19, 611–625 (1989).

  113. 113

    Leckman, J. F., Walker, D. & Cohen, D. Premonitory urges in Tourette's syndrome. Am. J. Psychiatry 150, 98–102 (1993).

  114. 114

    Woods, D. W., Piacentini, J., Himle, M. B. & Chang, S. Premonitory Urge for Tics Scale (PUTS): initial psychometric results and examination of the premonitory urge phenomenon in youths with tic disorders. J. Dev. Behav. Pediatr. 26, 397–403 (2005).

  115. 115

    Piacentini, J. et al. Behavior therapy for children with Tourette disorder: a randomized controlled trial. JAMA 303, 1929–1937 (2010). This is the first large-scale controlled evaluation of a comprehensive behavioural intervention for tics in children.

  116. 116

    Müller-Vahl, K. R., Riemann, L. & Bokemeyer, S. Tourette patients’ misbelief of a tic rebound is due to overall difficulties in reliable tic rating. J. Psychosomat. Res. 76, 472–476 (2014).

  117. 117

    Turtle, L. & Robertson, M. M. Tics, twitches, tales: the experiences of Gilles de la Tourette's syndrome. Am. J. Orthopsychiatry 78, 449 (2008).

  118. 118

    Cavanna, A. E. & Nani, A. Tourette syndrome and consciousness of action. Tremor Other Hyperkinet. Mov.http://dx.doi.org/10.7916/D8PV6J33 (2013).

  119. 119

    Patel, N., Jankovic, J. & Hallett, M. Sensory aspects of movement disorders. Lancet Neurol. 13, 100–112 (2014).

  120. 120

    Leckman, J. F. et al. The Yale Global Tic Severity Scale: initial testing of a clinician-rated scale of tic severity. J. Am. Acad. Child Adolesc. Psychiatry 28, 566–573 (1989). This is the first study to report the psychometric properties of the most widely used tic severity scale.

  121. 121

    Martino, D. et al. Systematic review of severity scales and screening instruments for tics: critique and recommendations. Mov. Disord.http://dx.doi.org/10.1002/mds.26891 (2017).

  122. 122

    Goetz, C. G., Pappert, E. J., Louis, E. D., Raman, R. & Leurgans, S. Advantages of a modified scoring method for the Rush Video-Based Tic Rating Scale. Mov. Disord. 14, 502–506 (1999).

  123. 123

    Gaffney, G. R., Sieg, K. & Hellings, J. The MOVES: a self-rating scale for Tourette's syndrome. J. Child Adolesc. Psychopharmacol. 4, 269–280 (1994).

  124. 124

    Baizabal-Carvallo, J. F. & Fekete, R. Recognizing uncommon presentations of psychogenic (functional) movement disorders. Tremor Other Hyperkinet. Mov. 5, 279–279 (2014).

  125. 125

    Baizabal-Carvallo, J. F. & Jankovic, J. The clinical features of psychogenic movement disorders resembling tics. J. Neurol. Neurosurg. Psychiatry 85, 573–575 (2014).

  126. 126

    Dreissen, Y., Cath, D. & Tijssen, M. Functional jerks, tics, and paroxysmal movement disorders. Handb. Clin. Neurol. 139, 247–258 (2017).

  127. 127

    Mejia, N. I. & Jankovic, J. Secondary tics and tourettism. Rev. Bras. Psiquiatr. 27, 11–17 (2005).

  128. 128

    Bloch, M. H. et al. Adulthood outcome of tic and obsessive–compulsive symptom severity in children with Tourette syndrome. Arch. Pediatr. Adolesc. Med. 160, 65–69 (2006). This is one of the first prospective longitudinal studies confirming that tic symptoms typically diminish in late adolescence.

  129. 129

    Leckman, J. F. et al. Course of tic severity in Tourette syndrome: the first two decades. Pediatrics 102, 14–19 (1998).

  130. 130

    Zinner, S. H., Conelea, C. A., Glew, G. M., Woods, D. W. & Budman, C. L. Peer victimization in youth with Tourette syndrome and other chronic tic disorders. Child Psychiatry Hum. Dev. 43, 124–136 (2012).

  131. 131

    Pappert, E. J., Goetz, C., Louis, E., Blasucci, L. & Leurgans, S. Objective assessments of longitudinal outcome in Gilles de la Tourette's syndrome. Neurology 61, 936–940 (2003).

  132. 132

    Jankovic, J., Gelineau-Kattner, R. & Davidson, A. Tourette's syndrome in adults. Mov. Disord. 25, 2171–2175 (2010).

  133. 133

    Eapen, V., Robertson, M. M., Alsobrook, J. P. & Pauls, D. L. Obsessive compulsive symptoms in Gilles de la Tourette syndrome and obsessive compulsive disorder. Am. J. Med. Genet. 74, 432–438 (1997).

  134. 134

    O’Rourke, J. A. et al. The familial association of tourette's disorder and ADHD: the impact of OCD symptoms. Am. J. Med. Genet. B Neuropsychiatr. Genet. 156, 553–560 (2011).

  135. 135

    Clarke, R. A. & Eapen, V. Balance within the neurexin trans-synaptic connexus stabilizes behavioral control. Front. Hum. Neurosci. 8, 52 (2014).

  136. 136

    Petek, E. et al. Molecular and genomic studies of IMMP2L and mutation screening in autism and Tourette syndrome. Mol. Genet. Genomics 277, 71–81 (2007).

  137. 137

    Delgado, M. S. et al. Screening individuals with intellectual disability, autism and Tourette's syndrome for KCNK9 mutations and aberrant DNA methylation within the 8q24 imprinted cluster. Am. J. Med. Genet. B Neuropsychiatr. Genet. 165, 472–478 (2014).

  138. 138

    Kwak, C., Vuong, K. D. & Jankovic, J. Migraine headache in patients with Tourette syndrome. Arch. Neurol. 60, 1595–1598 (2003).

  139. 139

    Bulik-Sullivan, B. et al. An atlas of genetic correlations across human diseases and traits. Nat. Genet. 47, 1236–1241 (2015).

  140. 140

    Robertson, M. M., Cavanna, A. E. & Eapen, V. Gilles de la Tourette syndrome and disruptive behavior disorders: prevalence, associations, and explanation of the relationships. J. Neuropsychiatry Clin. Neurosci. 27, 33–41 (2015).

  141. 141

    Robertson, M. M. Mood disorders and Gilles de la Tourette's syndrome: an update on prevalence, etiology, comorbidity, clinical associations, and implications. J. Psychosomat. Res. 61, 349–358 (2006).

  142. 142

    Pauls, D. L., Leckman, J. F. & Cohen, D. J. Evidence against a genetic relationship between Tourette's syndrome and anxiety, depression, panic and phobic disorders. Br. J. Psychiatry 164, 215–221 (1994).

  143. 143

    Eddy, C. M. & Cavanna, A. E. On being your own worst enemy: an investigation of socially inappropriate symptoms in Tourette syndrome. J. Psychiatr. Res. 47, 1259–1263 (2013).

  144. 144

    Kurlan, R. et al. Non-obscene complex socially inappropriate behavior in Tourette's syndrome. J. Neuropsychiatry Clin. Neurosci. 8, 311–317 (1996).

  145. 145

    Darrow, S. M. Identification of two heritable cross-disorder endophenotypes for Tourette syndrome. Am. J. Psychiatryhttp://dx.doi.org/10.1176/appi.ajp.2016.16020240 (2016).

  146. 146

    Hirschtritt, M. E. et al. Social disinhibition is a heritable subphenotype of tics in Tourette syndrome. Neurology 87, 497–504 (2016).

  147. 147

    Robertson, M. M. Movement disorders: Tourette syndrome — beyond swearing and sex? Nat. Rev. Neurol. 10, 6–8 (2014).

  148. 148

    Khalifa, N. & Von Knorring, A.-L. Psychopathology in a Swedish population of school children with tic disorders. J. Am. Acad. Child Adolesc. Psychiatry 45, 1346–1353 (2006).

  149. 149

    McGuire, J. F. et al. A cluster analysis of tic symptoms in children and adults with Tourette syndrome: clinical correlates and treatment outcome. Psychiatry Res. 210, 1198–1204 (2013).

  150. 150

    Storch, E. A. et al. Suicidal thoughts and behaviors in children and adolescents with chronic tic disorders. Depress. Anxiety 32, 744–753 (2015).

  151. 151

    Dávila, G., Berthier, M. L., Kulisevsky, J. & Chacón, S. J. Suicide and attempted suicide in Tourette's syndrome: a case series with literature review. J. Clin. Psychiatry 71, 1401–1402 (2010).

  152. 152

    Johnco, C. et al. Suicidal ideation in youth with tic disorders. J. Affect. Disord. 200, 204–211 (2016).

  153. 153

    Robertson, M. M., Eapen, V. & van de Wetering, B. J. Suicide in Gilles de la Tourette's syndrome: report of two cases. J. Clin. Psychiatry 56, 378 (1995).

  154. 154

    Murphy, T. K., Lewin, A. B., Storch, E. A., Stock, S. & American Academy of Child and Adolescent Psychiatry (AACAP) Committee on Quality Issues (CQI). Practice parameter for the assessment and treatment of children and adolescents with tic disorders. J. Am. Acad. Child Adolesc. Psychiatry 52, 1341–1359 (2013).

  155. 155

    Verdellen, C., van de Griendt, J., Hartmann, A., Murphy, T. & ESSTS Guidelines Group. European clinical guidelines for Tourette syndrome and other tic disorders. Part III: behavioural and psychosocial interventions. Eur. Child Adolesc. Psychiatry 20, 197–207 (2011).

  156. 156

    Scahill, L. et al. Current controversies on the role of behavior therapy in Tourette syndrome. Mov. Disord. 28, 1179–1183 (2013).

  157. 157

    Hartmann, A., Martino, D. & Murphy, T. Gilles de la Tourette syndrome — a treatable condition? Rev. Neurol. (Paris) 172, 446–454 (2016).

  158. 158

    Azrin, N. H. & Nunn, R. G. Habit reversal: a method of eliminating nervous habits and tics. Behav. Res. Ther. 11, 619–628 (1973).

  159. 159

    Woods, D. W. et al. Managing Tourette Syndrome: A Behavioral Intervention for Children and Adults (Therapist Guide) (Oxford Univ. Press, 2008).

  160. 160

    Steeves, T. et al. Canadian guidelines for the evidence-based treamtent of tic disorders: behavioural therapy, deep brain stimulation, and transcranial magnetic stimulation. Can. J. Psychiatry 57, 144–151 (2012).

  161. 161

    Wilhelm, S. et al. Randomized trial of behavior therapy for adults with Tourette syndrome. Arch. General Psychiatry 69, 795–803 (2012).

  162. 162

    Himle, M. B. et al. A randomized pilot trial comparing videoconference versus face-to-face delivery of behavior therapy for childhood tic disorders. Behav. Res. Ther. 50, 565–570 (2012).

  163. 163

    Ricketts, E. J. et al. A randomized waitlist-controlled pilot trial of voice over internet protocol-delivered behavior therapy for youth with chronic tic disorders. J. Telemed. Telecare 22, 153–162 (2016).

  164. 164

    Ricketts, E. J. et al. Pilot testing behavior therapy for chronic tic disorders in neurology and developmental pediatrics clinics. J. Child Neurol. 31, 444–450 (2016).

  165. 165

    Deckersbach, T. et al. Neural correlates of behavior therapy for Tourette's disorder. Psychiatry Res. 224, 269–274 (2014).

  166. 166

    Capriotti, M. R., Himle, M. B. & Woods, D. W. Behavioral treamtents for Tourette syndrome. J. Obsessive Compuls. Relat. Disord. 3, 415–420 (2014).

  167. 167

    Verdellen, C. W. J., Keijsers, G. P. J., Cath, D. C. & Hoogduin, C. A. L. Exposure with response prevention versus habit reversal in Tourette's syndrome: a controlled study. Behav. Res. Ther. 42, 501–511 (2004).

  168. 168

    Pringsheim, T. et al. Canadian guidelines for the evidence-based treatment of tic disorders: pharmacotherapy. Can. J. Psychiatry 57, 133–143 (2012).

  169. 169

    Macerollo, A. et al. Refractoriness to pharmacological treatment for tics: a multicentre European audit. J. Neurol. Sci. 366, 136–138 (2016).

  170. 170

    Hollis, C. et al. Clinical effectiveness and patient perspectives of different treatment strategies for tics in children and adolescents with Tourette syndrome: a systematic review and qualitative analysis. Health Technol. Assess. 20, 1–450 (2016).

  171. 171

    Whittington, C. et al. Practitioner review: treatments for Tourette syndrome in children and young people — a systematic review. J. Child Psychol. Psychiatry 57, 988–1004 (2016).

  172. 172

    Roessner, V. et al. Pharmacological treatment of tic disorders and Tourette syndrome. Neuropharmacology 68, 143–149 (2013).

  173. 173

    Weisman, H., Qureshi, I. A., Leckman, J. F., Scahill, L. & Bloch, M. H. Systematic review: pharmacological treatment of tic disorders — efficacy of antipsychotic and alpha-2 adrenergic agonist agents. Neurosci. Biobehav. Rev. 37, 1162–1171 (2013).

  174. 174

    Almandil, N. B. et al. Weight gain and other metabolic adverse effects associated with atypical antipsychotic treatment of children and adolescents: a systematic review and meta-analysis. Pediatr. Drugs 15, 139–150 (2013).

  175. 175

    Robertson, M. M. Gilles de la Tourette syndrome: the complexities of phenotype and treatment. Br. J. Hosp. Med. (Lond.) 72, 100–107 (2011).

  176. 176

    Kwak, C. H., Hanna, P. A. & Jankovic, J. Botulinum toxin in the treatment of tics. Arch. Neurol. 57, 1190–1193 (2000).

  177. 177

    Müller-Vahl, K. R. Treatment of Tourette syndrome with cannabinoids. Behav. Neurol. 27, 119–124 (2013).

  178. 178

    Zheng, Y. et al. A proprietary herbal medicine (5-Ling Granule) for Tourette syndrome: a randomized controlled trial. J. Child. Psychol. Psychiatry 57, 74–83 (2016). This is the largest randomized, double-blind, clinical trial ever completed for individuals 5–18 years of age with GTS (n = 603).

  179. 179

    Kim, Y. H. et al. Herbal medicines for treating tic disorders: a systematic review of randomised controlled trials. Chinese Med. 9, 6 (2014).

  180. 180

    Shprecher, D. R., Kious, B. M. & Himle, M. Advances in mechanistic understanding and treatment approaches to Tourette syndrome. Discov. Med. 20, 295–301 (2015).

  181. 181

    Andrade, P. & Visser-Vandewalle, V. DBS in Tourette syndrome: where are we standing now? J. Neural Transm. (Vienna) 123, 791–796 (2016).

  182. 182

    Hariz, M. I. & Robertson, M. M. Gilles de la Tourette syndrome and deep brain stimulation. Eur. J. Neurosci. 32, 1128–1134 (2010).

  183. 183

    Kim, W. & Pouratian, N. Deep brain stimulation for Tourette syndrome. Neurosurg. Clin. N. Am. 25, 117–135 (2014).

  184. 184

    Servello, D., Zekaj, E., Saleh, C., Lange, N. & Porta, M. Deep brain stimulation in Gilles de la Tourette syndrome: what does the future hold? A cohort of 48 patients. Neurosurgery 78, 91–100 (2016).

  185. 185

    Kefalopoulou, Z. et al. Bilateral globus pallidus stimulation for severe Tourette's syndrome: a double-blind, randomised crossover trial. Lancet Neurol. 14, 595–605 (2015). This is the largest randomized, double-blind, crossover trial of globus pallidus interna DBS for severe GTS (n = 15).

  186. 186

    Deeb, W. et al. Proceedings of the Fourth Annual Deep Brain Stimulation Think Tank: a review of emerging issues and technologies. Front. Integr. Neurosci. 10, 38 (2016).

  187. 187

    Elstner, K., Selai, C., Trimble, M. & Robertson, M. M. Quality of life (QOL) of patients with Gilles de la Tourette's syndrome. Acta Psychiatr. Scand. 103, 52–59 (2001).

  188. 188

    Cavanna, A. et al. The Gilles de la Tourette syndrome-Quality of Life Scale for children and adolescents (C&A-GTS-QOL): development and validation of the Italian version. Behav. Neurol. 27, 95–103 (2013).

  189. 189

    Cavanna, A. et al. The Gilles de la Tourette syndrome–Quality of Life Scale (GTS-QOL) development and validation. Neurology 71, 1410–1416 (2008).

  190. 190

    Cavanna, A. et al. Health-related quality of life in Gilles de la Tourette syndrome: a decade of research. Behav. Neurol. 27, 83–93 (2013).

  191. 191

    Eapen, V., Snedden, C., Črnčec, R., Pick, A. & Sachdev, P. Tourette syndrome, co-morbidities and quality of life. Aust. N. Z. J. Psychiatry 50, 82–93 (2016).

  192. 192

    Evans, J., Seri, S. & Cavanna, A. E. The effects of Gilles de la Tourette syndrome and other chronic tic disorders on quality of life across the lifespan: a systematic review. Eur. Child Adolesc. Psychiatry 25, 939–948 (2016).

  193. 193

    O’Hare, D., Helmes, E., Reece, J., Eapen, V. & McBain, K. The differential impact of Tourette's syndrome and comorbid diagnosis on the quality of life and functioning of diagnosed children and adolescents. J. Child Adolesc. Psychiatr. Nurs. 29, 30–36 (2016).

  194. 194

    Eapen, V., Cavanna, A. E. & Robertson, M. M. Comorbidities, social impact, and quality of life in Tourette syndrome. Front. Psychiatry 7, 97 (2016). This comprehensive review summarizes the literature on the impact of GTS and related comorbidities from social and QOL perspectives.

  195. 195

    Muller-Vahl, K. et al. Health-related quality of life in patients with Gilles de la Tourette's syndrome. Mov. Disord. 25, 309–314 (2010).

  196. 196

    Eddy, C. et al. Quality of life in young people with Tourette syndrome: a controlled study. J. Neurol. 258, 291–301 (2011).

  197. 197

    Swain, J. E., Scahill, L., Lombroso, P. J., King, R. A. & Leckman, J. F. Tourette syndrome and tic disorders: a decade of progress. J. Am. Acad. Child Adolesc. Psychiatry 46, 947–968 (2007).

  198. 198

    Bawden, H. N., Stokes, A., Camfield, C. S., Camfield, P. R. & Salisbury, S. Peer relationship problems in children with Tourette's disorder or diabetes mellitus. J. Child Psychol. Psychiatry 39, 663–668 (1998).

  199. 199

    O’Hare, D. et al. Factors impacting the quality of peer relationships of youth with Tourette's syndrome. BMC Psychol. 3, 34 (2015).

  200. 200

    Conelea, C. et al. The impact of Tourette syndrome in adults: results from the Tourette syndrome impact survey. Community Ment. Health J. 49, 110–120 (2013).

  201. 201

    Parisi, J. Engagement in adulthood: perceptions and participation in daily activities. Act. Adapt. Aging 34, 1–16 (2010).

  202. 202

    Haddad, A., Umoh, G., Bhatia, V. & Robertson, M. M. Adults with Tourette's syndrome with and without attention deficit hyperactivity disorder. Acta Psychiatr. Scand. 120, 299–307 (2009).

  203. 203

    O’Hare, D. et al. Youth with Tourette syndrome: parental perceptions and experiences in the Australian context. Aust. J. Psychol.http://dx.doi.org/10.1111/ajpy.12111 (2016).

  204. 204

    Cooper, C., Robertson, M. M. & Livingston, G. Parental stress and burden in parents of children with Gilles de la Tourette syndrome compared with parents of children with asthma. J. Am. Acad. Child Adolesc. Psychiatry 42, 1370–1375 (2003).

  205. 205

    Levinson, D. F. et al. Genetic studies of major depressive disorder: why are there no GWAS findings, and what can we do about it? Biol. Psychiatry 76, 510–512 (2014).

  206. 206

    Schizophrenia Psychiatric Genome-Wide Association Study Consortium. Genome-wide association study identifies five new schizophrenia loci. Nat. Genet. 43, 969–976 (2011).

  207. 207

    Sanders, S. J. et al. Insights into autism spectrum disorder genomic architecture and biology from 71 risk loci. Neuron 87, 1215–1233 (2015).

  208. 208

    Roden, D. M. et al. Development of a large-scale de-identified DNA biobank to enable personalized medicine. Clin. Pharmacol. Ther. 84, 362–369 (2008).

  209. 209

    Robinson, E. B. et al. Genetic risk for autism spectrum disorders and neuropsychiatric variation in the general population. Nat. Genet. 48, 552–555 (2016).

  210. 210

    Darrow, S. M. et al. Web-based phenotyping for Tourette syndrome: reliability of common co-morbid diagnoses. Psychiatry Res. 228, 816–825 (2015).

  211. 211

    National Institute of Mental Health. Strategic research priorities. NIMHhttps://www.nimh.nih.gov/about/strategic-planning-reports/strategic-research-priorities/srp-objective-1/priorities-for-strategy-12.shtml (2016).

  212. 212

    Kundaje, A. et al. Integrative analysis of 111 reference human epigenomes. Nature 518, 317–330 (2015).

  213. 213

    Miller, J. A. et al. Transcriptional landscape of the prenatal human brain. Nature 508, 199–206 (2014).

  214. 214

    Gamazon, E. R. et al. A gene-based association method for mapping traits using reference transcriptome data. Nat. Genet. 47, 1091–1098 (2015).

  215. 215

    Willsey, A. J. et al. Coexpression networks implicate human midfetal deep cortical projection neurons in the pathogenesis of autism. Cell 155, 997–1007 (2013).

  216. 216

    Hibar, D. P. et al. Common genetic variants influence human subcortical brain structures. Nature 520, 224–229 (2015).

  217. 217

    Singer, H. S. et al. Elevated intrasynaptic dopamine release in Tourette's syndrome measured by PET. Am. J. Psychiatry 159, 1329–1336 (2002). In this study, greater putamen dopamine release was seen in adults with GTS than in control subjects.

  218. 218

    Baldermann, J. C. et al. Deep brain stimulation for Tourette-syndrome: a systematic review and meta-analysis. Brain Stimul. 9, 296–304 (2016).

  219. 219

    Deeb, W. et al. The International Deep Brain Stimulation Registry and Database for Gilles de la Tourette syndrome: how does it work? Front. Neurosci. 10, 170 (2016).

  220. 220

    Termine, C., Selvini, C., Rossi, G. & Balottin, U. Emerging treatment strategies in Tourette syndrome: what's in the pipeline. Int. Rev. Neurobiol. 112, 445–480 (2013).

  221. 221

    Shapiro, A. K., Shapiro, E. S., Bruun, R. D. & Sweet, R. D. Gilles de la Tourette Syndrome (Raven Press Books, 1978).

  222. 222

    Cavanna, A. E. & Piedad, J. C. P. in Tourette Syndrome (eds Martino, D. & Leckman, J. F. ) 411–438 (Oxford Univ. Press, 2013).

  223. 223

    King, R. & Landeros-Weisenberger, A. in Tourette Syndrome(eds Martino, D. & Leckman, J. F. ) 402–410 (Oxford Univ. Press, 2013).

  224. 224

    Rosario, M. C. et al. Validation of the University of São Paulo sensory phenomena scale: initial psychometric properties. CNS Spectr. 14, 315–323 (2009).

  225. 225

    Leckman, J. F., Walker, D. E., Goodman, W. K., Pauls, D. L. & Cohen, D. J. “Just right” perceptions associated with compulsive behavior in Tourette's syndrome. Am. J. Psychiatry 151, 675–680 (1994).

Download references

Acknowledgements

The authors acknowledge all their patients and their families for their time, patience and teaching us all more about Gilles de la Tourette syndrome.

Author information

Introduction (M.M.R.); Epidemiology (M.M.R.); Mechanisms/ pathophysiology (H.S.S., D.M., P.P. and J.M.S.); Diagnosis, screening and prevention (M.M.R. and J.F.L.); Management (V.R., D.W.W. and M.H.); Quality of life (V.E. and R.Č.); Outlook (J.M.S., C.A.M. and V.E.); Overview of Primer (M.M.R. and V.E.).

Correspondence to Mary M. Robertson or Valsamma Eapen.

Ethics declarations

Competing interests

J.M.S. has received consulting fees from Nuvelution Pharma. D.W.W. receives royalties from Guilford Press and Oxford University Press and has received funding from the US National Institute of Mental Health (NIMH) through a subcontract with PsycTech. M.H. has received honoraria and travel grants from Medtronic as a speaker. J.F.L. serves on the scientific advisory boards of the Brain and Behavior Research Foundation, the European Multicentre Tics in Children Studies, the National Organization for Rare Diseases, Fondazione Child, and How I Decide. He has also received royalties from John Wiley and Sons, McGraw-Hill and Oxford University Press. M.M.R., V.E., H.S.S., D.M., P.P., V.R., C.A.M. and R.Č. declare no competing interests.

PowerPoint slides

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Robertson, M., Eapen, V., Singer, H. et al. Gilles de la Tourette syndrome. Nat Rev Dis Primers 3, 16097 (2017) doi:10.1038/nrdp.2016.97

Download citation

Further reading