Girls with RTT are born without any sign of the disease and appear to develop normally for the first six to 18 months of life. Then they begin to regress, sometimes abruptly, losing their burgeoning skills in muscle control and communication. Eventually the disease stabilizes, and the girls grow up with extensive mental retardation and a propensity to sit and wring their hands.
"I saw my first RTT patient as a pediatric neurology fellow in October 1983, though I didn't yet know what it was," said Zoghbi. "I was amazed by two things. First, her history of normal development followed by a period of regression. Second, I can't think of another neurological disease in which patients will sit there and endlessly wring their hands."
A week later, Zoghbi was scheduled to see a young girl who had been diagnosed with cerebral palsy. This patient too was wringing her hands. "I thought that since I saw two in one week, there must be more," Zoghbi said. Examination of patient records revealed six more girls with similar signs: hand-wringing, ataxia and spasticity.
RTT has been her biggest challenge, Zoghbi said, largely because only one percent of recorded cases are inherited. Researchers have a much easier time homing in on a defective gene when they are working with large families with numerous affected members.
While 99 percent of RTT cases occur randomly in the population, Zoghbi's
starting hypothesis was logical: If the syndrome strikes only girls, whose
sex-determining chromosomes are XX, and not boys, whose sex is determined by the
X and Y chromosomes, then the defect must reside in a gene carried on the X
chromosome. Furthermore, Zoghbi reasoned that the gene was both
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
1-Oct-1999