Tourette Syndrome is a hereditary neurological movement disorder that is characterized by repetitive motor and vocal tics. Symptoms may include involuntary movements of the extremities, shoulders, and face accompanied by uncontrollable sounds and, in some cases, inappropriate words. Tourette Syndrome is neither a progressive nor degenerative disorder; rather, symptoms tend to be variable and follow a chronic waxing and waning course throughout an otherwise normal life span. The specific symptoms associated with Tourette Syndrome often vary greatly from case to case. The exact cause of Tourette Syndrome is unknown.
Tourette Syndrome usually begins in childhood with a twitch (tic) of a facial muscle. A tic is an involuntary repetitive muscle movement. These tics often include excessive eye blinking, nose twitching, or grimacing. Other gestures may include involuntary head shaking, shoulder jerking, arm flapping, or foot stomping. In very rare severe cases, tics may involve self-mutilating behaviors such as lip biting, nail biting, or hair pulling.
Some individuals with Tourette Syndrome may also experience certain vocal (phonic) tics such as repeated throat clearing, grunting, coughing, hissing, and/or involuntary repetition of certain words or phrases. The repetition of obscene words (coprolalia) occurs in approximately 15 percent of affected individuals, in some cases, coprolalia may occur for only a short period (such as several months). Involuntary repetition of a word or phrase spoken by another person (echolalia) may also occur. Individuals with Tourette Syndrome are vulnerable to mirroring the behavior (echopraxia) and speech (echolalia) of others, as well as repeating their own words (palilalia).
Tics may subside when an affected individual is focused on a particular task; in addition, tics may intensify during times of stress. During the course of the disease, certain symptoms may cease to occur while others may emerge. In some cases, new symptoms may begin to occur in association with other symptoms that are already present.
Some affected individuals may have associated behavioral manifestations, particularly obsessive compulsive behaviors. Compulsions are repetitive actions or rituals performed in response to recurrent obsessive thoughts. Such behaviors may be performed to help relieve obsessive thoughts, to reduce anxieties, and/or to avoid some anticipated, dreaded situation. (For more information on this disorder, see the “Related Disorders” section below.)
The exact cause of Tourette syndrome is currently unknown. Clinical researchers at Yale University Medical School have identified a gene on Chromosome 13 that appears to be associated with some forms of Tourette syndrome. This gene is thought to be involved in the growth of nerve cells (neurons) in the brain’s cortex and in the basal ganglia.
A number of researchers suggest that the disorder may be inherited as an autosomal dominant genetic trait with incomplete penetrance and variable expression. Human traits, including the classic genetic diseases, are the product of the interaction of two genes for that condition, one received from the father and one from the mother.
In dominant disorders, a single copy of the disease gene (received from either the mother or father) will be expressed “dominating” the other normal gene, usually resulting in the appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child. The risk is the same for each pregnancy.
Most individuals affected by Tourette syndrome have mild cases. In some instances, individuals with a defective gene for Tourette syndrome may not exhibit symptoms at all (incomplete penetrance). In addition, in those cases where individuals with a defective gene for the disorder do have symptoms associated with Tourette syndrome, the characteristics may vary greatly in range and severity from case to case (variable expressivity). According to reports in the medical literature, the varying penetrance and expressivity of the disease gene for the disorder may be suggested by the fact that tic conditions and obsessive compulsive behavior, which are often associated with Tourette syndrome, also occur with increased frequency among first-degree relatives of individuals with the disorder. In addition, some affected children may have a mild form of Tourette syndrome or symptoms that remit after adolescence. In all cases, the range and severity of associated symptoms cannot be predicted.
According to the medical literature, researchers suggest that Tourette syndrome may be due to inheritance of the gene in combination with certain environmental factors that may trigger the abnormal gene’s expression (multifactorial inheritance). Such researchers speculate that individuals who inherit two copies of a disease gene for the disorder (homozygotes) will usually express the disorder, while those who inherit just one disease gene (heterozygotes) may not develop Tourette syndrome unless certain environmental factors (e.g., infection) trigger expression of the gene.
For example, researchers theorize that certain infections may trigger the development of Tourette syndrome in some individuals who are genetically susceptible to the disease. One study suggests that infection with certain bacteria may result in an abnormally high immune response that causes a sudden onset of obsessive compulsive disorder and Tourette syndrome symptoms. A leading candidate is a common group of bacteria that causes strep throat and rheumatic fever (Group A beta-hemolytic streptococcus). This bacterial infection is also known to cause a similar movement disorder known as Syndenham’s chorea. (For more information on this disorder, see the Related Disorders section below.)
The specific underlying abnormalities that result in the symptoms associated with Tourette syndrome are currently unknown. However, some research has suggested that abnormal metabolism of certain chemicals in the brain such as dopamine and serotonin (i.e., biochemical imbalance of neurotransmitter systems) may play some role in causing the symptoms of the disorder.
More research is needed to further investigate the potential roles of specific genetic factors, certain infectious organisms, and/or certain biochemical imbalances that may play a role in causing the symptoms associated with Tourette syndrome.
In 1999, the Tourette Syndrome Association’s International Consortium for Tourette Syndrome Genetics announced that scientists have identified markers on two chromosomes that point to specific areas where Tourette syndrome related genes may be found. Scientists in the Tourette Syndrome Association’s International Consortium will now map the genes located in these areas of chromosomes 4 and 8.
A recent genomewide study has indicated that several genes of moderate effect may increase an individual’s susceptibility to developing Tourette syndrome. More studies are necessary to confirm these findings and determine the specific locations (loci) of such genes.
Tourette Syndrome typically begins during childhood between the ages of two and 16 years. In rare cases, symptoms may occur in children as young as one year of age or become apparent after 16 years of age. The male to female ratio is four to one. Tourette Syndrome occurs in all ethnic groups. The National Institutes of Health estimates that there are approximately 100,000 cases of Tourette Syndrome in the United States, although the prevalence may be much higher if all mild cases of tics are counted (e.g. chronic multiple tics and/or transient childhood tics). Other estimates range from one in 20,000 to one in 2,000 depending upon the particular age and diagnostic criteria used by individual studies.
The diagnosis of Tourette Syndrome may be suspected based upon a thorough clinical evaluation and a detailed patient history.
Low doses of the drug haloperidol (Haldol) help suppress the motor symptoms of Tourette Syndrome in many cases. Side effects often limit the use of this drug.
Clonidine (Catapres), used for the treatment of hypertension, appears to be effective on motor, vocal, and behavioral symptoms in a number of of individuals with Tourette Syndrome. In some cases, a closely related drug, guanfacine (Tenex), may be used with fewer side effects.
Pimozide (Orap) is an approved orphan drug with Dopamine D-2 blocking action. Pimozide is reported to be as effective as Haldol with fewer side effects in some individuals with Tourette Syndrome. Other dopamine blocking drugs (i.e., prolixin) are also used to reduce the symptoms associated with Tourette Syndrome.
Other medications used to treat symptoms of Tourette Syndrome include. tricyclic antidepressants such as imipramine (Tofranil), desipramine (Norpramin), and nortriptyline (Pamelor). Medications used to treat the obsessive compulsive symptoms of Tourette Syndrome include. fluoxetine (Prozac), clomipramine (Anafranil), and sertraline (Zoloft).
Supportive psychotherapy may be indicated to foster an affected individual's adjustment to this chronic, socially difficult disorder.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.
For information about clinical trials being conducted at the National Institutes of Health (NIH) Clinical center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
For information about clinical trials sponsored by private sources, contact:
Three drugs are (2006) in late-stage trials for the treatment of individuals with Tourette syndrome. Topiramate is in a Phase III trial sponsored by Baylor College of Medicine and Ortho-McNeil Neurologies, Inc., to determine its effectiveness in improving the symptoms of Tourette syndrome, such as motor tics or obsessive-compulsive problems. For information about this study, contact Cynthia Studenko at (713) 798-9014 or firstname.lastname@example.org or Christine Hunter, RN, at (713) 798-3951 or email@example.com.
A Phase IV study of the drug galantamine began in 2005 and is expected to continue until 2007. The purpose is to study this drug’s effectiveness in reducing tics and attention- or obsessive-related disorders. This study is sponsored by the Parkinson’s Disease and movement Disorders Center of Albany Medical Center and Ortho-McNeil Neurologics. For information, contact Donald S. Higgins, MD, at (518) 452-0914 or firstname.lastname@example.org.
New York University School of Medicine is sponsoring a Phase IV clinical trial of the drug aripiprazole for reducing symptoms of Tourette syndrome in children and adolescents ages 7 to 18. For information, go to the Clinical Trials web site or contact Rachel Shechter at (212) 263-3654 or Rachel.email@example.com or Adeena Gabriel at (212) 263-8679 or firstname.lastname@example.org.
In April 2004, a Tourette syndrome patient was treated with deep brain stimulation at the University Hospitals of Cleveland Health System, affiliated with Case Western Reserve University. This new surgical approach involves implanting electrodes deep within the brain that are attached to pacemakers and may help to control involuntary muscle movements. This was the first time that this surgical treatment, which has been approved by the U.S. Food and Drug Administration for treating Parkinson disease, essential tremor, and dystonia, was performed on a Tourette syndrome patient in North America. Additional study is needed to determine its safety and effectiveness for Tourette syndrome patients who have not been helped by other treatments and whose quality of life is being severely impacted. For information, contact:
Eileen Korey (University Hospitals Health System)
Phone: (216) 844-3825
In 2003, the FDA granted orphan drug status to atomoxetine hydrochloride (Strattera) for the treatment of Tourette syndrome. Strattera is an approved treatment for attention deficit disorder and is manufactured by the Eli Lilly Corporation. For information, contact the company:
Phone: (317) 276-2000
Geneticists have identified several large families (kindreds) with many members affected by Tourette syndrome. Recent genetic research on affected siblings has produced data pointing to two potential chromosomes where the defective gene may be located. It is hoped that studies of these families may lead to identification of the gene that causes the disorder.
Researchers are seeking families with two siblings who have Tourette syndrome to participate in a gene identification study. For more information, contact the Tourette Syndrome Association (which is listed in the Resources section of this report below).
One study has suggested that the use of a smoking cessation aid (i.e., nicotine patch) in combination with existing drug therapy may help to decrease the frequency of motor and vocal tics. More studies are needed to determine the long-term safety and effectiveness of this treatment.
The drug mecamylamine (Inversine) has received an orphan drug designation from the U.S. Food and Drug Administration (FDA) as a treatment for Tourette syndrome. Originally sponsored by Layton Biosciences, Inc., Inversine was purchased by Targacept in 2002. For information, contact:
200 East First Street
Winston-Salem, NC 27101-4165
Tel: (336) 480-2100
In the March 2000 issue of the Journal of the American Academy of Child and Adolescent Psychiatry, researchers from Pfizer Central Research in Groton, Ct., reported that the drug ziprasidone may be a safe alternative for treating pediatric Tourette syndrome patients. Although somewhat less effective than traditional neuroleptics, it was tolerated better by children and adolescents and reduced the severity and frequency of tic symptoms.
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McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:137580; Last Update:4/12/2002.