by Monica Coenraads
Anyone who knows anything about Rett Syndrome knows that the disorder is primarily seen in girls. The disorder is caused by disruption of the MECP2 gene located on the X chromosome. Girls have two X chromosomes one with the disrupted gene and one with the healthy gene. Having some healthy MeCP2 protein allows girls to survive but at the expense of severe impairment that comes with Rett.
Since boys only have the one X chromosome they have no healthy MECP2 at all. These boys typically have a more severe form of the disease and often die in early childhood. (There are genetic situations that allow boys to present like classic girls with Rett, for example if they have Klinefelter Syndrome which gives them two Xs.)
The fact that boys only have one X is the reason most often given for why Rett is seen in girls. However this is not accurate. While having the sole X is the reason boys often succumb to the disease it is NOT the reason why Rett is primarily a woman’s disease. That reason has to do with where the MECP2 mutation originates.
Many studies over the past decade have provided evidence that the vast majority of MECP2 mutations originate in the sperm. Since fathers give an X to their daughters and a Y chromosome to their sons the MECP2 mutation can only be transmitted from father to daughter. This is the reason why Rett is seen primarily in girls.
Boys, on the other hand, get their MECP2 mutations from their mother, a situation that arises only rarely. (Mutations can also originate in a single cell as the male embryo is developing.)
Scientific papers over the years have hypothesized that because male fetuses only have one X their disease would be so severe that they might not even develop to full term and the mothers might miscarry. There is no clinical data to support this hypothesis whatsoever.
Due to the sheer volume of sperm that is continuously made it is likely that all men produce sperm with MECP2 mutations. One in about 20,000 eggs will be fertilized with a sperm that has an MECP2 mutation in it – the cruel reality of genetic roulette.