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Tourette Disorder Overview

Synonyms: Gilles de la Tourette Syndrome, Maladie de Tics, Tourette Syndrome

, PhD, , PhD, and , MD, PhD.

Author Information
, PhD
Program on Neurogenetics
Department of Genetics
Yale University School of Medicine
New Haven, Connecticut
, PhD
Program on Neurogenetics
Child Study Center
Yale University School of Medicine
New Haven, Connecticut
, MD, PhD
Program on Neurogenetics
Department of Genetics
Child Study Center
Yale University School of Medicine
New Haven, Connecticut

Initial Posting: .


Clinical characteristics.

Tourette disorder (TD) is defined by the presence for more than a year of multiple motor tics and at least one vocal tic. Tics are sudden, rapid, recurrent, nonrhythmic, stereotyped motor movements or vocalizations. Individuals with either vocal or motor tics (but not both) for more than a year are given diagnoses of chronic vocal tics (CVT) or chronic motor tics (CMT), respectively. The onset of Tourette disorder is in early childhood with symptoms typically peaking before puberty and showing marked improvement by adulthood. Tourette disorder often co-occurs with other neuropsychiatric disorders, most notably attention deficit hyperactivity disorder (ADHD) and/or obsessive-compulsive disorder (OCD), and it is often these co-occurring, or comorbid conditions that bring affected individuals to medical attention.


The American Psychiatric Association Manual of Psychiatric Disorders (DSM-IV-TR) is the primary diagnostic reference for TD used in the US. Strong evidence implicates genetics in the pathogenesis of TD; however, no definitive locus has been confirmed to date. SLITRK1 is one of several genes thought to be associated with TD; however, molecular genetic testing of SLITRK1 is of little or no clinical relevance based on current knowledge.

Genetic counseling.

Recurrence risk counseling is based on empiric familial risk for families with individuals with Tourette disorder. It is estimated that the rate of TD among first-degree relatives of an individual with TD is 10%-15%.


Treatment of manifestations: Tailored to the individual. Medications, including dopamine antagonists and alpha-2 adrenergic agonists, as well as behavioral therapies, particularly habit reversal therapy, have been shown to be effective. The management of comorbid disorders, either with pharmacotherapy or behavioral and psychological treatments, often takes precedence over tic suppression in the treatment of affected individuals.


Clinical Manifestations of Tourette Disorder

Gilles de la Tourette [1885] first described individuals with chronic vocal and motor tics. To this day, the eponymous syndrome is defined by the persistence of unwanted, brief, repetitive, non-rhythmic motor movements and vocalizations. Common motor tics include eye blinking and facial grimacing; common vocal tics include throat clearing, sniffing, or grunting.

Tics that involve a single muscle or a small group of muscles are considered “simple”; those that include a coordinated pattern of movement or sound and resemble purposeful action or speech are considered “complex.”

A small minority of affected individuals experience coprolalia, or the uttering of obscenities, a symptom that is often erroneously portrayed in the media as pathognomonic for TD [Robertson 1994, Albin & Mink 2006, Mathews et al 2007].

By diagnostic criteria, tics in TD occur many times a day, usually in bouts, for at least one year. Past diagnostic systems included an impairment criterion [American Psychiatric Association 2000], but the most recent diagnostic system (DSM-IV-TR, 2000) has eliminated the impairment criterion.

Individuals who experience:

  • Tics that persist for more than four weeks but less than a year meet criteria for transient tic disorder.
  • Persistent motor movements in the absence of vocal tics meet criteria for chronic motor tic disorder (CMT)
  • Persistent vocalizations in the absence of motor tics meet criteria for chronic vocal tic disorder (CVT)

Note: (1) Often, the latter two categories are combined into a single group designated simply chronic tics (CT). (2) It is presumed that all of these persistent tic disorders share some common etiologic mechanism, and thus represent a spectrum.

The typical age of onset for TD is between three and eight years (mean age ~7 years) with onset of motor tics most often preceding vocal tics. The syndrome is characterized by a waxing and waning course with peak symptom intensity noted typically in late childhood (mean age 10 years) [Gadow et al 2002, Fusco et al 2006]. Tics tend to fluctuate in frequency, intensity, and type, and to crescendo and then diminish through late adolescence. In fact, the majority of affected persons demonstrate significant improvement by early adulthood with only approximately 22% continuing to experience functional impairment after age 20 years [Bloch et al 2006].

Several additional aspects of Tourette disorder are notable:

  • The majority of affected individuals have the ability to suppress some of the movements and vocalizations for brief periods of time. Ultimately, however, tics are irrepressible. The ability to suppress some tics for brief periods of time may cause observers to misunderstand the syndrome, particularly early in the course of illness. Parents and teachers of affected children often presume incorrectly that the symptoms are volitional or even purposely disruptive.
  • Tics are frequently preceded by a “premonitory urge” or a sense of inner tension that is reduced or relieved by the performance of the tic [Banaschewski et al 2003, Kwak et al 2003]. The negative reinforcing effect of completing the tic may partially shape tic severity over time [Conelea & Woods 2008]. This characteristic is also typical of obsessive-compulsive disorder (OCD), in which a feeling of heightened anxiety accompanies the sensation that a particular action may reduce or relieve the anxiety. The areas of clinical, genetic, and neurobiologic overlap between TD and OCD are discussed below.
  • The high degree of psychiatric comorbidity is relevant to both clinical assessment and phenotypic assignment in genetic studies. The vast majority of individuals who present to clinic for evaluation and treatment of TD have other psychiatric disorders. For example, ADHD occurs in 50%-90% of TD probands seen in clinical settings [Leckman 2003, Burd et al 2005, Comings et al 2005, Stewart et al 2006, Freeman 2007, Roessner et al 2007, Ghanizadeh & Mosallaei 2009]. However, the rate of co-occurrence is 20%-50% in community-ascertained samples based on parent or teacher questionnaires [Khalifa & von Knorring 2003, Scahill et al 2005].

    The onset of ADHD typically precedes the onset of tics and may be associated with academic, social, and family difficulties [Spencer et al 2001, Sukhodolsky et al 2003]. ADHD symptoms often persist into adulthood despite the tendency for tics to diminish.
  • OCD is also commonly observed in individuals with TD referred for clinical evaluation, with recent studies suggesting that up to 50% of individuals with TD show evidence of both disorders [do Rosário & Miguel Filho 1997, Ghanizadeh & Mosallaei 2009]. Moreover, the rates of OCD appear to be increased in family members, particularly among families of female probands [Miguel et al 2005]. “Tic-related” OCD may represent an OCD subtype [Miguel et al 2005] comprising a characteristic constellation of obsessions such as intrusive images and sounds and compulsive touching, tapping, staring, and blinking [Summerfeldt et al 2004].
  • Difficulties with learning are common in children and adolescents with TD. Parents of children with TD and ADHD also have been observed to demonstrate an elevated rate of language-based learning problems
  • Certain habit disorders are observed frequently in clinically referred individuals with TD. Trichotillomania (chronic hair pulling) (4%), pathologic nail biting (25%), and pathologic skin picking are more common in individuals with TD and OCD than in the general population [Bienvenu et al 2000, Lochner et al 2005].
  • Mood disorders are also present at higher frequencies in individuals with TD [Robertson 2006]. Dysthymia, major depressive disorder (MDD), and depressive illness occur in 13%-76% of persons with TD attending specialty clinics. Bipolar disorder (BPD) has been reported in 7%-28% of the TD population [Kerbeshian et al 1995, Spencer et al 1995], although the diagnostic criteria for BPD in children and adolescents are the subject of some debate.
  • Individuals with TD experience increased anxiety compared to those who do not have TD. Community-based studies comparing children with tics to children without tics found significantly elevated rates of a variety of anxiety disorders including separation anxiety, simple phobia, social phobia, and agoraphobia [Kurlan et al 2002]. An Increased prevalence of anxiety disorders has also been observed in clinically ascertained samples, even when OCD is not considered [Coffey et al 2000].

The relative contributions of genetic, neurobiologic, psychological, or environmental influences to these wide-ranging comorbid disorders are not yet clear. As discussed in more detail below, family genetic studies have supported the hypothesis that TD and some cases of OCD demonstrate a common genetic diathesis [Pauls 1992], while the issue of a common genetic component to ADHD is considered more controversial [Pauls et al 1986].

Establishing the Diagnosis of Tourette Disorder

The standard diagnostic criteria for Tourette disorder in the US are defined by the American Psychiatric Association Manual of Psychiatric Diseases, 4th edition Text Revision (DSM-IV-TR) [American Psychiatric Association 2000].

Diagnostic criteria for Tourette disorder include the following:

  • Both multiple motor tics and one or more vocal tics have been present at some time during the illness, although not necessarily concurrently. (A tic is a sudden, rapid, recurrent, nonrhythmic, stereotyped motor movement or vocalization.)
  • The tics occur many times a day (usually in bouts) nearly every day or intermittently throughout a period of more than one year; during this period tic-free periods do not exceed more than three consecutive months.
  • The onset is before age 18 years.
  • The disturbance is not due to the direct physiologic effects of a substance (e.g., stimulants) or a general medical condition (e.g., Huntington disease or post-viral encephalitis).
  • For a child who fulfills all criteria except psychological dysfunction or distress, the International Classification of Diseases (ICD) criteria can be used instead of a DSM diagnosis.

Diagnostic criteria for transient tic disorder (TDD) include the following:

  • Single or multiple motor and/or vocal tics are present.
  • The tics occur many times a day, nearly every day for at least four weeks, but for no longer than 12 consecutive months.
  • The onset is before age 18 years.
  • The disturbance is not due to the direct physiologic effects of a substance or a general medical condition.
  • Criteria have never been met for Tourette disorder or chronic motor or vocal tic disorder.

Diagnostic criteria for chronic motor or vocal tic disorder include the following:

  • Single or multiple motor or vocal tics, but not both, have been present at some time during the illness.
  • The tics occur many times a day nearly every day or intermittently throughout a period of more than one year, and during this period no tic-free period exceeds more than three consecutive months.
  • The onset is before age 18 years.
  • The disturbance is not due to the direct physiologic effects of a substance or a general medical condition.
  • Criteria have never been met for Tourette disorder.

Diagnostic criteria for tic disorder not otherwise specified:

  • This category is for disorders characterized by tics that do not meet criteria for a specific tic disorder. Examples include tics lasting less than four weeks or tics with onset after age 18 years.

Diagnostic tools. The diagnosis of TD is made clinically based on the history, pattern, and intensity of the symptoms. No laboratory tests can confirm the presence of tics or determine a specific recurrence risk, apart from those that establish alternative diagnoses (see Differential Diagnosis). In rare instances, EEG may be useful to differentiate tics from seizure activity.

Several research instruments are widely used to establish severity ratings. These instruments may also be useful in clinical settings to document the character and severity of symptoms and to help track symptom trajectory over time.

The most commonly referenced clinician-administered inventory is the Yale Global Tic Severity Scale (YGTSS) [Leckman et al 1989, American Psychiatric Association 2000].

Standardized assessment of obsessive-compulsive symptoms can be accomplished with (e.g.) the Yale Brown Obsessive Compulsive Scale by Goodman et al [1989] or the Children’s Yale Brown Obsessive Compulsive Scale by Scahill et al [1997].

Differential Diagnosis

The primary issue in differential diagnosis is distinguishing tics from other movement disorders including chorea, dystonia, myoclonus, dyskinesias, or stereotypies. In practice, differentiating TD from other neurologic conditions is usually not difficult. For instance, vocal tics are uncommon with the rare exception of Huntington disease and Sydenham chorea. The observation of tics during sleep with a normal neurologic examination, the ability to temporarily suppress the tics, the presence of premonitory urges, and a diminution of tics with intentional movement are all distinctive of TD [Leckman & Cohen 1998]. In addition, the clinical history is quite suggestive: early onset and waxing, waning, and fluctuating symptoms as well as the co-occurrence of simple and complex tics are all highly suggestive of the diagnosis. Indeed the presentation of an individual with an unusual history of, for example, late onset or the presence of complex tics in the absence of a history of simple tics should warrant further investigation.

With regard to other neuropsychiatric diagnoses, the presence of complex motor tics may be difficult to distinguish from compulsive rituals. In the clinic, a distinction is often drawn between ego-dystonic repetitive behaviors that are related to a specific thought (e.g., to reduce concerns about harm befalling a person) which are considered symptoms of OCD, versus those that arise in response to a feeling of tension or a premonitory urge which are classified as complex tics. If making the distinction between OCD and TD is a priority, it is helpful to recall that simple tics are observed in nearly all cases of TD and their absence would raise the index of suspicion for an alternative diagnosis.

Prevalence of Tourette Disorder

TD was initially thought to be rare. However, more recent studies using epidemiologic ascertainment strategies and standardized instruments now place the prevalence of TD at approximately 0.3%-1% [Robertson 2008a]. Motor tics are quite common with point prevalence estimates of between 7% and 28%.

Males are affected far more often than females, with an approximate 4:1 ratio [Freeman 2007, Robertson 2008a]

TD is observed worldwide and most extensively studied populations show similar prevalence, ranging from approximately 0.5%-4% among children ages 5 to 18 years. However, lower rates have been noted in African Americans and in Sub-Saharan Africa [Robertson 2008a, Robertson 2008b]. The degree to which these lower figures may represent methodologic confounds, including ascertainment biases, remains in question.

Causes of Tourette Disorder

Molecular mechanisms underlying TD remain largely unknown. Strong and consistent evidence support the predominant role of genetics in its etiology; however, to date no loci have been definitively confirmed for TD. Twin studies also support a significant role for non-genetic contributions. The most widely investigated area in this regard is the role of streptococcal infection in TD and related conditions.


From its initial description the familial nature of TD has been well appreciated. Gene mapping and discovery efforts have been ongoing for several decades [Kidd et al 1980, Pauls et al 1981]. MZ (monozygotic) twin concordance rates are approximately 50% compared to 10% for DZ (dizygotic) twins. When the entire range of tic disorders is considered, concordance rates for MZ twins reach 77% compared to 23% for DZ twins [Price et al 1985].

Despite long-standing consensus that genetics plays the leading role in disease etiology, considerable debate and uncertainty remain regarding the nature of these genetic contributions. Given findings in other complex, relatively common conditions, current hypotheses focus on the potential contribution of both common and rare genetic variants. Studies using linkage analysis, gene association studies, and molecular cytogenetic approaches have identified several candidate regions and transcripts.

Linkage Studies

Early studies focused on large multigenerational pedigrees that suggested autosomal dominant inheritance [Baron et al 1981, Kidd & Pauls 1982, Pauls & Leckman 1986, Curtis et al 1992]. However, over time, as the techniques and resolution of mapping loci responsible for single gene disorders improved and no TD locus was identified, the single gene hypothesis was abandoned.

Subsequent segregation analyses reported by Kurlan et al [1994], Hasstedt et al [1995], and Walkup et al [1996] led to the current emerging consensus that TD is a complex, heterogeneous genetic disorder. Of note, the rate of TD spectrum disorders (TD, obsessive-compulsive disorder, and chronic tics) in bilineal families (i.e., present in both maternal and paternal lineages) is estimated to be as high as 36% when considering families with more than one affected child [McMahon et al 1996].

By the late 1990s, the failure of pedigree-based (parametric) linkage analyses to identify a TD-related locus resulted in a shift to nonparametric linkage analysis, which does not require a genetic model and often focuses on analyses of affected sib pairs (ASP). In 1999, the Tourette Syndrome Association International Consortium for Genetics (TSAICG) reported that linkage analysis of 92 ASPs from 76 nuclear families gave multipoint maximum-likelihood scores above 2 on chromosome 4q (D4S1625) and chromosome 8 (D8S1145, D8S1106, D8S136). However, when the study was extended to 238 ASPs and 18 large families, the linkage at these loci was not significant. Evidence for linkage emerged on chromosome 2p for individuals with TD or complex tics. For the analyses in the ASP sample affected with TD only, moderate evidence (multipoint maximum-likelihood scores ≥2) (i.e., p<1X10-2) was found for markers on chromosomes 2p, 3p, 3q, 4p, 6p, 10p, 15p, 21p, and Xp [TSAICG 1999, TSAICG 2007]. This collection of ASPs is continuing to be expanded and fine mapping efforts are underway.

While several additional studies yielded LOD scores above 2.5 [Mérette et al 2000, Curtis et al 2004, Paschou et al 2004], these have yet to be replicated and to date none has led to the identification of pathogenic variants within transcripts mapping to these intervals.

Association Studies

Association studies comparing allele frequencies in individuals with TD have been reported on a number of biologically plausible candidate genes including the dopamine receptor genes, the dopamine transporter (SLC6A3), several noradrenergic genes, tyrosine hydroxylase (TH), and various serotonergic genes [Brett et al 1995, Barr et al 1996, Chou et al 2004]. As has often been the case across all of medicine, associations identified in these studies of a single or small number of candidate loci have not been reproducible.

Genome-wide association studies (GWAS), a methodology that has proven far more effective than other methods in establishing the contribution of common low-risk alleles to complex diseases, are currently underway.

Cytogenetic Studies

Several reports have described chromosomal abnormalities in individuals with TD. Only a handful of those reported have disrupted a transcript, clustered in a given region of the genome, or had putative pathogenic variants identified in a nearby gene:

To date, four cytogenetic findings in individuals with TD spectrum disorders, including TD, OCD, and chronic tics (CT), have been reported involving the chromosome 18q22 region.


SLITRK1 was first implicated as a candidate gene for TD in a rare variant study in 2005 [Abelson et al 2005]. Since that initial report multiple studies have examined both common and rare variants in TD populations with mixed results. Evaluation of a larger TD cohort is still necessary to determine if sequence variants of SLITRK1 are associated with increased risk for TD. The following briefly details the genetic findings for SLITRK1 thus far.

Abelson et al [2005] reported on a de novo chromosome 13 inversion inv(13)(q31.1;q33.1) in a child with no family history of TD. The 13q33.1 breakpoint was mapped approximately 350 kb from the gene SLITRK1. A screen of 174 unrelated individuals with TD for pathogenic variants in SLITRK1 identified a single nucleotide deletion, NM_052910.1:c.1264delC that predicted a prematurely truncated SLITRK1 protein (p.Leu422Phefs*28). This deletion segregated with TD and trichotillomania (TTM) within the small family and, unlike the wild-type SLITRK1 protein, the mutant protein failed to promote dendritic growth in primary cortical neurons. Additionally, the authors found two independent occurrences (corroborated by haplotype analysis) of a rare G>A variant in a highly conserved region of the 3’UTR of SLITRK1 (NM_052910.1:c.*689G>A; trivial name var321). The region containing the pathogenic variant was shown to function as a binding site for the microRNA hsa-miR-189. In vitro analyses demonstrated that this rare variant leads to reduced expression of the target transcript. The authors proposed that rare functional variants of SLITRK1 may be associated with an increased risk for TD.

Two follow-up studies [Keen-Kim et al 2006, Scharf et al 2008] called into question the association of the 3’UTR variant, (NM_052910.1:c.*689G>A; trivial name var321) reported by Abelson et al [2005]. These investigators raised the possibility that c.*689G>A was either restricted to or over-represented among Ashkenazi Jews and that population stratification led to a false positive result. However, the fact that neither of the two individuals identified in the Abelson et al study reported Ashkenazi ethnicity, shared an extended haplotype, or clustered with Ashkenazi Jewish populations strongly argued against population stratification as a confounding issue in the initial report.

Sequence analysis in a cohort of individuals with trichotillomania (TTM) identified two individuals with novel SLITRK1 sequence variants that predicted amino acid substitutions not present in a group of more than 2000 unaffected individuals [Zuchner et al 2006].

In contrast to the above association studies of rare SLITRK1 variants and TD, several groups have tested the alternative hypothesis that there may be an association between SLITRK1 common alleles and TD. Results to date have been equivocal, with one positive study [Miranda et al 2009] and another larger study yielding no evidence for association [Scharf et al 2008].

Recent studies have identified an evolutionarily conserved and developmentally regulated pattern of SLITRK1 expression in frontal-subcortical circuits, regions highly suspect in the neuropathology of TD [Stillman et al 2009]. In addition, the Slitrk1 knockout mouse has been reported to show increased anxiety and abnormalities in noradrenergic neurotransmission [Katayama et al 2010].

Environmental Influences

As the concordance rate of TD among MZ twins is not 100%, non-genetic factors are certain to influence the expression of TD; however, identifying specific environmental causes or contributors has proven as difficult as identifying specific disease-related genes.

Leckman et al [1990] suggested that a high degree of maternal stress and severe nausea and vomiting during the first trimester may be contributory.

Maternal smoking during pregnancy has also been proposed as a strong risk factor for comorbid OCD and increased tic severity in TD [Mathews et al 2006].

Others have not found a statistically significant difference in pre- and perinatal complications between individuals with TD and matched controls [Khalifa & von Knorring 2005].

Hyde et al [1992] found a significant effect of birth weight on the TD phenotype in a study of 12 twin pairs in which the smaller twin had more severe TD ratings on the Shapiro scale than the larger twin (P<0.05).

A post-infectious etiology for TD and tics has been postulated for more than a decade [Kushner et al 1999]. Most recently, this hypothesis has centered on post-streptococcal infection. It is well known that group A beta hemolytic strep (GABHS) can lead to rheumatic heart disease. Central nervous system involvement, referred to as Sydenham chorea (SC), may accompany the cardiac and joint lesions. In addition to classic choreiform movements, individuals with SC also experience vocal and motor tics as well as attention problems, hyperactivity, obsessions, and compulsions. These findings along with their own clinical observations led Swedo et al [2004] to propose that pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) represent a distinct clinical entity with defining characteristics that include a temporal association between symptom onset or exacerbation and GABHS infection, the presence of OCD and/or tics, a prepubertal age of onset, the abrupt emergence and a relapsing-remitting course of symptoms, and the presence of associated adventitious movements or hyperactivity.

Since this initial description, PANDAS has remained a controversial topic, with studies providing both confirmatory and contradictory evidence. For instance:

  • In a relatively large and well-controlled study, Mell et al [2005] reported that multiple streptococcal infections in a 12-month period were associated with a substantial increase in risk for TD (OR=13.6; 95% CI: 1.93-51.0).
  • In contrast, neither Luo et al [2004] nor Perrin et al [2004] found evidence of increased tics after GABHS infection.
  • A prospective case control study reported that only a small number of clinical exacerbations of tics and/or OCD symptoms were temporally associated with streptococcal infection [Kurlan et al 2008].
  • Results of various treatment trials based on the GABHS hypothesis have also been equivocal [Garvey et al 1999, Perlmutter et al 1999, Hoekstra et al 2004, Snider et al 2005]. A number of studies have focused on putative molecular mechanisms including “mimicry” (in which a GABHS-related antibody targets human neuronal epitopes), altered cytokine production, or altered immune suppression. Studies in these areas have been intriguing at times; however, in most cases findings have not been consistently replicated across laboratories [Singer et al 1998, Morshed et al 2001, Singer et al 2005].

Unknown Cause

As noted, while both genetic and environmental factors appear to contribute to the pathophysiology of TD, the molecular mechanisms remain unknown. Although the overall understanding of TD has advanced, the vast majority of cases are of unknown origin.

Evaluation Strategy

Once the diagnosis of Tourette disorder has been established in an individual, the following approach can be used to facilitate discussions of prognosis and genetic counseling.

Family history. A standard three-generation family history should be obtained with attention to the range of comorbid disorders, including learning problems, ADHD, OCD, mood disorders, and non-OCD anxiety disorders. Up to 40% of pedigrees with multiple affected children were found to have bilineal inheritance of TD and OCD.

Molecular genetic testing. Sequence analysis of SLITRK1 is possible. However, while the SLITRK1 transcript and its function remain interesting areas of investigation, it is not yet possible to provide a clear interpretation of results obtained from SLITRK1 sequence analysis.

If there are atypical findings in the history, such as spells of absence or unilateralization of tics, neurologic consultation and workup is indicated.

Genetic Counseling

Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members. This section is not meant to address all personal, cultural, or ethical issues that individuals may face or to substitute for consultation with a genetics professional. —ED.

Mode of Inheritance

While evidence implicates a genetic component in the pathogenesis of Tourette disorder (TD), no loci have been definitively confirmed to date. Available data suggest a complex multifactorial etiology, possibly including interactions of genetic and environmental factors. At present, genetic counseling based on empiric familial risk is the only available strategy for the families of children with TD in the absence of autism spectrum disorder or developmental delay.

Empiric Risk to Family Members

Parents of a proband. The rate of TD in the parents of a proband ranges from 6.5% to 16%, with fathers demonstrating a much higher risk (11.9%-23.1%) compared to mothers (1%-9.6%). The rate of chronic tics for both parents ranges from 11.5% to 21%; the rate of OCD for both parents ranges from 10% to 23.1% [Pauls et al 1991, Walkup et al 1996]. A Japanese population study, however, found the rate of TD for both parents was 1.9% and the rate of tics for both parents was approximately 11.5% [Kano et al 2001]. Therefore, while the epidemiologic data so far suggest similar prevalence figures worldwide, it is nonetheless possible that the rate of TD and other related disorders and the risks to first-degree relatives may vary in specific populations.

Sibs of a proband. Sibs have approximately an 8% risk of TD and a 9.7% to 22% risk of OCD. The risk for sibs for chronic tics ranges from 0% to 11% [Pauls et al 1991, Walkup et al 1996]. The empiric risk for TD found in a Japanese cohort was lower (2.3%) than in other studies [Kano et al 2001].

Offspring of a proband. The empiric risk to offspring of a proband with TD was reported as 22% for TD and greater than 50% for a tic disorder [McMahon et al 2003].

In bilineal families the risk of TD for offspring increased to 42.8% compared to 15% for unilineal families. Additionally, rates of any tic diagnosis, OCD, and ADHD were increased [McMahon et al 2003].

Related Genetic Counseling Issues

DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, allelic variants, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals.


GeneReviews staff has selected the following disease-specific and/or umbrella support organizations and/or registries for the benefit of individuals with this disorder and their families. GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here.

  • Medline Plus
  • My46 Trait Profile
  • National Institute of Neurological Disorders and Stroke (NINDS)
    PO Box 5801
    Bethesda MD 20824
    Phone: 800-352-9424 (toll-free); 301-496-5751; 301-468-5981 (TTY)
  • National Library of Medicine Genetics Home Reference
  • Tourette Syndrome "Plus"
  • Tourette Syndrome Association (TSA)
    42-40 Bell Boulevard
    Bayside NY 11361
    Phone: 718-224-2999
    Fax: 718-279-9596
  • Tourette Syndrome Foundation of Canada
    5945 Airport Road
    Suite 195
    Mississauga Ontario L4V 1R9
    Phone: 800-361-3120 (toll-free); 905-673-2255
    Fax: 800-387-0120 (toll-free); 905-673-2638


Evaluations Following Initial Diagnosis

To establish the extent of disease in an individual diagnosed with Tourette disorder (TD), the following clinical examinations are recommended:

  • An inventory of tics and obsessive-compulsive symptoms
  • Measures such as the YGTSS and CYBOCs to document symptoms and assist in determining the degree of impairment
  • Given the high rate of psychiatric comorbidity, systematic screening for other childhood-onset neuropsychiatric disorders including ADHD, learning problems, mood disorders, and non-OCD anxiety symptoms. Reports by self, teacher, and parent are widely used to assist in this evaluation [Leckman & Cohen 1998].

The new onset of a movement disorder warrants a general neurologic examination. As noted in Differential Diagnosis, the presence of frank deficits should raise suspicion of an alternative diagnosis and prompt referral to a movement disorder specialist. In addition, episodic changes in consciousness or other evidence of seizure activity are not consistent with a diagnosis of TD and require appropriate referral.

Treatment of Manifestations

Pharmacotherapy. Medications have been used to successfully suppress tics in individuals with TD for four decades. Nonetheless, a cure remains illusive and the limitations of contemporary pharmacotherapy are notable. In general, the treatment of TD centers not only on management of tic symptoms, but typically must also address one or more psychiatric comorbidities, most often ADHD, OCD, depression, and anxiety.

The pharmacologic treatment of TD and chronic tics is significantly complicated by the waxing, waning, and fluctuating course of the illness. As tics tend to occur in bouts with marked crescendos followed by spontaneous diminution of symptoms, it is often difficult for a patient, parent, or clinician to discern whether a medication is influencing the course of illness over a short period of time. Indeed as affected individuals may not come to attention until tics approach “worst-ever” severity, typically precisely at the time that symptoms would be likely to diminish, it is not uncommon for an initial trial of pharmacotherapy to appear to result in dramatic improvement which is then followed by the reemergence or exacerbation of tics over time.

Both typical and atypical neuroleptics have been shown in double blind placebo-controlled trials to lead to significant reduction in tic symptoms in persons with TD. Typical neuroleptics are first-generation antipsychotics that are categorized by their chemical structure (e.g., haloperidol, pimozide), whereas atypical neuroleptics are second-generation antipsychotics that are classified by pharmacologic properties (e.g., risperidone). The only two medications labeled for treatment of tics in TD are haloperidol and pimozide. Tic suppression among typical neuroleptics is best predicted by strong dopamine (DA) D2 antagonism; thus, atypical neuroleptics such as clozapine that have relatively weak receptor binding do not appear to be effective. However, the second-generation neuroleptic risperidone has been studied in controlled trials for TD and found to be efficacious. Although DA antagonists can be beneficial in the short run in suppressing unwanted tics, the majority of patients treated with these agents experience side effects including sedation, weight gain, dysphoria, and cognitive dulling [Singer et al 1995, Leckman et al 2001]. On the other hand, the atypical neuroleptics are of particular concern with regard to the long-term risks for weight gain, metabolic abnormalities, and diabetes mellitus.

Given both the waxing and waning nature of tics in TD and the known short- and long-term side effects of DA antagonists, treatment should be undertaken judiciously, with an effort to maintain the lowest effective dose and to limit the time of exposure, particularly in children. Moreover, it is important for the clinician to approach treatment with a broad perspective mindful that tics show significant improvement as affected individuals enter mid to late adolescence, and that the associated comorbid disorders are often of greater clinical concern than the unwanted movements and vocalizations.

Alpha 2 adrenergic agonists, including clonidine and guanfacine, are currently considered first-line pharmacotherapy for TD and chronic tic disorders. Although alpha 2 adrenergic agonists are not labeled to treat TD, evidence from controlled trials supports that these are effective, particularly for mild to moderate symptoms [Leckman et al 1991, Scahill et al 2000, Scahill et al 2006]. Side effects are typically benign and include sedation, light-headedness, and at times irritability.

A variety of other medications has been reported to be helpful either alone or in combination with the therapies noted above. The evidence for efficacy is modest in several including benzodiazepines, baclofen, and tetrabenzine, and would benefit from additional controlled trials.

Botulinum toxin, evaluated in several open studies and one double blind study, has been shown to be effective, particularly in suppression of an isolated tic. Adverse effects include soreness at the injection and weakness of the injected muscle, including the vocal cords, which may lead to hypophonia [Scahill et al 2006].

For a time nicotine was regarded as a potential treatment, but so far studies have been unconvincing.

Behavior therapy. At present, the most thoroughly investigated behavioral treatment for TD is habit reversal therapy, which involves increasing an individual’s awareness of his/her tics and substituting a competing response that is inconsistent with performance of the unwanted action. The habit reversal approach is a multi-component treatment that includes self-monitoring, relaxation training, development of competing responses, awareness training, and contingency management [Wilhelm et al 2003, Himle et al 2006]. Several blinded trials have supported the efficacy of this approach, with symptom reductions rivaling those seen with medications. Results to date, including a recently completed NIH controlled study, have been quite promising [O’Connor et al 2009].

Other cognitive behavioral approaches, including exposure and response prevention, have been less well studied, but have shown some promising results.

In contrast, relaxation therapy does not seem to be effective when used alone [Bergin et al 1998], but may be beneficial when used in combination with other behavioral approaches [Wilhelm et al 2003, Woods et al 2003].

Therapies Under Investigation

Surgical therapy. Surgical intervention has been utilized for a small subset of individuals with intractable TD, in whom conventional therapy has been unsuccessful and in whom the tics have been harmful. The most successful intervention has been deep brain stimulation (DBS), which involves implanting electrodes in specific targeted regions in the brain. These electrodes then send out electrical impulses altering brain activity in that region. Since it is hypothesized that tics arise from an imbalance within the cortico-striato-thalamo-cortical pathway, the thalamus, globus pallidus pars interna, and nucleus accumbens have been targeted in DBS [Flaherty et al 2005, Houeto et al 2005, Ackermans et al 2006]. Overall, individuals treated with DBS have experienced a reduction in tics, both in frequency and in intensity, without major side effects. It is difficult to weigh the benefits of this intervention since only 34 individuals with TD have undergone DBS [Ackermans et al 2008]. Additionally the optimal target within the brain has yet to be elucidated.

Repetitive transcranial magnetic stimulation (rTMS). Repetitive transcranial magnetic stimulation is a non-invasive therapy in which targeted regions of the brain are stimulated using rapidly changing magnetic fields. This method has been shown to alter cortical activity: high-frequency stimulation increases cortical excitability; low-frequency stimulation invokes cortical inhibition. Different paradigms for rTMS have been examined in pilot studies in control populations [Fitzgerald et al 2006, Cattaneo & Silvanto 2008, Di Lazzaro et al 2008, Krause & Straube 2008] as well as in populations affected with neurologic and psychiatric disorders [Fregni & Pascual-Leone 2007, George et al 2007, Fitzgerald & Daskalakis 2008]. In the few studies that have utilized rTMS to treat symptoms of TD, both positive [Mantovani et al 2006] and negative results [Münchau et al 2002, Orth et al 2005] have been reported. Further clinical studies are required to address questions regarding optimal approach to treatment and efficacy. Given initial positive results and its noninvasiveness, rTMS remains an attractive area for investigation.

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Chapter Notes

Revision History

  • 10 November 2009 (me) Review posted live
  • 16 March 2009 (mws) Original submission
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