The Genetics of Tourette Syndrome
by Adam T. McGruther

In 1825, Georges Gilles de la Tourette, a French neurologist, diagnosed a woman with the first case of what would come to be known as Tourette Syndrome (TS).1 She exhibited symptoms such as facial tics, sudden outbursts of obscene language, and the repetition of things that were said to her. Since then, we have learned that TS is a genetically inherited disorder that may affect as many as 1 in 100 people, making it one of the most common genetic disorders known to man.1 In order to better explain TS, a case study will be utilized to give the reader a clear example of the implications of TS within a family.
While much is known about the symptoms of TS, the mode of inheritance is still very complicated model. TS is believed to be an autosomal dominant disorder, meaning that the gene (or genes) that causes the disorder is located on one of the chromosomes numbered 1-22, and not on one of the sex chromosomes (X,Y).1 The reason that genes was placed in parenthesis is that recent studies have indicated that the disorder may not be limited to one gene, but have multifactoral implications.2 Since TS is a dominant disorder, those individuals who are homozygous for the disorder (TT, this refers to the presence of the gene(s) for TS on two paired chromosomes) are affected, as well as those who are heterozygous (Tt). However, the expressiveness of the gene(s), and hence the disorder is variable. Of the individuals who have the Tt genotype, only 2.2% of males and 0.3% of females are affected with the disorder.2 These numbers, however, are subject to change based on the interpretation of what qualifies as TS. Recent literature has expanded the scope of TS to include the following symptoms:2
motor and/or vocal tics
sleep disorders
obsessive/compulsive behavior
learning disabilities
ADD (attention deficit disorder)
Motor tics are generally the most common symptom associated with TS. In individuals with TS, multiple motor and vocal tics are usually observed, as well as some of the other behavioral symptoms mentioned. The tics can be classified as:3
motor: eye blinking, shoulder shrugging, head jerking, facial grimacing
vocal: throat clearing, yelping, tongue clicking, sniffing
motor: jumping, twirling about, touching others, self-injurious behaviors
vocal: uttering words or phrases out of context (obscenities or racial slurs)
It is important to realize, however, while as many in 1 in 100 people may have TS (TT or Tt), very few actually manifest the complex tics or multiple symptoms.
As mentioned before, the inheritance model is very complicated, and is best explained using a case study. Since the disorder is dominant, it tends to affect entire familial lines, and can be seen across the generations. Consider Mike and Carrie Riley; happy parents of six children, but confused by their childrenís peculiar habits. Two of their boys, Greg and Ken, both tend to repeat what is said to them, and both have been in trouble in school for yelling out obscenities in class. Two of their other children, Alicia and Kate, both have problems with constant fidgeting, which disrupts their ability to sit still in school. For years Mike and Carrie had attributed their boy's behavior to childhood mischievousness, and dismissed their girlís actions since both Mike and his mother, Rita, exhibited the same behavior. Mike and Carrieís other two children, Joe and Cindy, have shown no signs of any behavior similar to their siblings.
Mike's sister, Suzanne, and her husband, Adam, also have a couple of children with peculiar habits. Their son, Steve, is dyslexic, and is very poor at math. One of their daughters, Edie, constantly takes showers or is washing her hands. Their other child, Jenny, seems to exhibit no strange behavior or learning disabilities.
While all of these cases seem to be unrelated, when one considers the broad definition of TS, a common thread can be seen throughout the Riley family. Suppose Rita is TT, meaning that she has full blown Tourette syndrome. If she married a man who was Tt, a carrier with no symptoms, any children they would have would be either TT or Tt. Mike, who has TS, is probably TT, and his sister, Suzanne, is probably Tt, but is not affected. Supposing that Adam is tt, he does not have TS and is not a carrier, Steve and Edie are probably Tt and are affected with TS. It is probable that their third child, Jenny, is also tt and therefore will not have TS. As for Mikeís children, since Carrie is probably tt, all of their children are Tt. However, since TS is expressed variably, not all of the children will necessarily develop the disorder (Joe and Cindy), and those that do have varying degrees of severity in their symptoms.
Obviously there is a great deal of uncertainty in trying to diagnose Tourette syndrome. Many of it's symptoms are common to one or more other neurological disorders. Unfortunately, however, until the gene(s) responsible for Tourette syndrome is found, and a genetic test developed, much of the guesswork associated with this disorder will continue.

1Merz, Beverly, Journal of the American Medical Association, vol. 260, no. 18, pg 2619.
2Walkup, J.T., LaBuda, M.C., Singer, H.S., Brown, J., Riddle, M.A., Hurko, O., American Journal of Human Genetics, 59:684-693, 1996.

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