Editing Tourette syndrome (section)

== Causes ==
{{Main|Causes and origins of Tourette syndrome}}
The exact cause of Tourette's is unknown, but it is well established that both genetic and environmental factors are involved.<ref name= Fernandez /><ref name= Dale2017 /><ref name= Baldermann /> [[Genetic epidemiology]] studies have shown that Tourette's is highly heritable,<ref name= Cavenna2018 /> and 10 to 100 times more likely to be found among close family members than in the general population.<ref name= Efron2018 /> The exact mode of inheritance is not known; no single gene has been identified,<ref name= EuropeanPartI/> and hundreds of genes are likely involved.<ref name=Bloch2011/><ref name= Cavenna2018>{{cite journal |vauthors=Cavanna AE |title=The neuropsychiatry of Gilles de la Tourette syndrome: The ''état de l'art'' |journal=Rev. Neurol. (Paris) |volume=174 |issue=9 |pages=621–627 |date=November 2018 |pmid=30098800 |doi=10.1016/j.neurol.2018.06.006 |s2cid=51966823 |type= Review}}</ref><ref name= Efron2018>{{cite journal |vauthors=Efron D, Dale RC |title=Tics and Tourette syndrome |journal=J Paediatr Child Health |volume=54 |issue=10 |pages=1148–1153 |date=October 2018 |pmid=30294996 |doi=10.1111/jpc.14165 |hdl=11343/284621 |s2cid=52934981 |type= Review|hdl-access=free }}</ref> [[Genome-wide association study|Genome-wide association studies]] were published in 2013<ref name=Stern2018 /> and 2015<ref name=Dale2017 /> in which no finding reached a threshold for significance;<ref name=Stern2018 /> a 2019 [[meta-analysis]] found only a single genome-wide significant locus on chromosome 13, but that result was not found in broader samples.<ref>{{cite journal |vauthors=Yu D, Sul JH, Tsetsos F, et al |title=Interrogating the genetic determinants of Tourette's syndrome and other tic disorders through genome-wide association studies |journal=Am J Psychiatry |volume=176 |issue=3 |pages=217–227 |date=March 2019 |pmid=30818990 |pmc=6677250 |doi=10.1176/appi.ajp.2018.18070857 |type= Meta-analysis}}</ref> [[Twin study|Twin studies]] show that 50 to 77% of [[monozygotic|identical twins]] share a TS diagnosis, while only 10 to 23% of [[dizygotic|fraternal twins]] do.<ref name=Fernandez /> But not everyone who inherits the genetic vulnerability will show symptoms.<ref>{{cite journal |vauthors=van de Wetering BJ, Heutink P |title=The genetics of the Gilles de la Tourette syndrome: a review |journal=J. Lab. Clin. Med. |volume=121 |issue=5 |pages=638–645 |date=May 1993 |pmid=8478592 |type= Review}}</ref><ref>{{cite journal |vauthors=Paschou P |title=The genetic basis of Gilles de la Tourette Syndrome |journal=Neurosci Biobehav Rev |volume=37 |issue=6 |pages=1026–1039 |date=July 2013 |pmid=23333760 |doi=10.1016/j.neubiorev.2013.01.016 |s2cid=10515751 |type= Review}}</ref> A few rare [[penetrance|highly penetrant]] genetic [[mutations]] have been found that explain only a small number of cases in single families (the ''[[SLITRK1]], [[Histidine decarboxylase|HDC]]'', and ''[[CNTNAP2]]'' genes).<ref>{{cite journal |vauthors=Barnhill J, Bedford J, Crowley J, Soda T |title=A search for the common ground between Tic; Obsessive-compulsive and Autism Spectrum Disorders: part I, Tic disorders |journal=AIMS Genet |volume=4 |issue=1 |pages=32–46 |date=2017 |pmid=31435502 |pmc=6690237 |doi=10.3934/genet.2017.1.32 |type= Review}}</ref>

[[Psychosocial]] or other non-genetic factors—while not causing Tourette's—can affect the severity of TS in vulnerable individuals and influence the expression of the inherited genes.<ref name= Hollis /><ref name=Zinner /><ref name= Baldermann /><ref name= Efron2018 /> Pre-natal and peri-natal events increase the risk that a tic disorder or comorbid OCD will be expressed in those with the genetic vulnerability. These include paternal age; [[forceps delivery]]; stress or severe nausea during pregnancy; and use of [[smoking and pregnancy|tobacco]], caffeine, [[alcohol during pregnancy|alcohol]],<ref name= Hollis /><ref name= Ueda2021/> and [[Cannabis (drug)|cannabis]] during pregnancy.<ref name= Stern2018 /> Babies who are born [[Preterm birth|premature]] with [[low birthweight]], or who have low [[Apgar score]]s, are also at increased risk; in premature twins, the lower birthweight twin is more likely to develop TS.<ref name= Hollis /><!-- p. 6 -->

[[Autoimmune]] processes may affect the onset of tics or exacerbate them. Both OCD and tic disorders are hypothesized to arise in a subset of children as a result of a post-[[streptococcus|streptococcal]] autoimmune process.<ref name=Hsu2021/> Its potential effect is described by the controversial<ref name=Hsu2021/> hypothesis called [[PANDAS]] (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections), which proposes five criteria for diagnosis in children.<ref name= Wilbur2019>{{cite journal |vauthors=Wilbur C, Bitnun A, Kronenberg S, Laxer RM, Levy DM, Logan WJ, Shouldice M, Yeh EA |title=PANDAS/PANS in childhood: Controversies and evidence |journal=Paediatr Child Health |volume=24 |issue=2 |pages=85–91 |date=May 2019 |pmid=30996598 |pmc=6462125 |doi=10.1093/pch/pxy145}}</ref><ref name=Sigra2018>{{cite journal |vauthors=Sigra S, Hesselmark E, Bejerot S |title=Treatment of PANDAS and PANS: a systematic review |journal=Neurosci Biobehav Rev |volume=86 |issue= |pages=51–65 |date=March 2018 |pmid=29309797 |doi=10.1016/j.neubiorev.2018.01.001 |s2cid=40827012 |doi-access=free }}</ref> PANDAS and the newer pediatric acute-onset neuropsychiatric syndrome (PANS) hypotheses are the focus of clinical and laboratory research, but remain unproven.<ref name= Wilbur2019/> There is also a broader hypothesis that links immune-system abnormalities and [[immune dysregulation]] with TS.<ref name= Dale2017 /><ref name= Hsu2021>{{cite journal |vauthors=Hsu CJ, Wong LC, Lee WT |title=Immunological dysfunction in Tourette syndrome and related disorders |journal=Int J Mol Sci |volume=22 |issue=2 |date=January 2021 |page=853 |pmid=33467014 |pmc=7839977 |doi=10.3390/ijms22020853 |type= Review|doi-access=free }}</ref>

Some forms of OCD may be genetically linked to Tourette's,<ref name=Swain /> although the genetic factors in OCD with and without tics may differ.<ref name= Fernandez /> The genetic relationship of ADHD to Tourette syndrome, however, has not been fully established.<ref name= Hirsch2015/><ref name=Denckla /><ref>{{cite journal |vauthors=Hirschtritt ME, Darrow SM, et al |title=Genetic and phenotypic overlap of specific obsessive-compulsive and attention-deficit/hyperactive subtypes with Tourette syndrome |journal=Psychol Med |volume=48 |issue=2 |pages=279–293 |date=January 2018 |pmid=28651666 |pmc=7909616 |s2cid=26353939 |doi=10.1017/S0033291717001672 }}</ref> A genetic link between autism and Tourette's has not been established as of 2017.<ref name= Robertson2017 />