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RETT SYNDROME (RTT) is a progressive neurodevelopmental disorder that almost exclusively affects females. It has an incidence of about 1 in 10,000 births, making it one of the most common causes of profound mental retardation in girls. Individuals with RTT develop normally until the age of 6 to 18 months, when they begin to lose purposeful use of their hands and speech. Affected individuals also show reduced muscle tone, wringing hand movements, autistic-like behavior and seizures.
A gene which causes RTT, MeCP2, has been found on the long arm of chromosome X (Xq28). Normally, females have two X chromosomes and males have an X and a Y. Since males do not have an additional copy of X to offset a defect, most X-linked diseases affect males. Then, why are males not affected by RTT? One possible explanation is that the absence of a functional copy of MeCP2 is lethal to the male fetus before birth. Researchers have shown this to be the case in a mouse model. Another question is why females are affected by RTT, even though one of their X chromosomes is normal. This is likely due to X inactivation, a normal process whereby one X chromosome is randomly inactivated in every cell. This partial deficiency - where the normal copy of MECP2 is active in some cells and inactive in others - allows girls with RTT to survive and develop normally during early infancy.
MeCP2 is believed to code for a protein which controls gene expression in the cell. Although it is not clear what the mechanism is, partial loss of this protein may lead to over expression of certain genes, leading to the RTT phenotype. With the discovery of MeCP2, investigators hope to develop a test for RTT which will allow for early diagnosis, prenatal detection and, ultimately, presymptomatic therapy.
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Revised April 19, 2000