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Female-to-Male Sex Reversal Found in 3 U.K. Family Members
By Daniel J. DeNoon
WebMD Health News
Reviewed by Laura J. Martin, MD
Both brothers are married to women, and they and their uncle have the sexual anatomy, behavior, growth, and skeletal development of males. All have normal health and intelligence.
What happened? During normal male development, the Y chromosome triggers a flood of gene interactions that is managed by the SOX9 gene. Once triggered, male development continues even in the absence of the Y chromosome.
This unusual case report, from University of Cambridge geneticist James J. Cox and colleagues, appears in the Jan. 6 issue of the New England Journal of Medicine.
While it's extremely rare for sex reversal to run in a family, it's not unheard of for genetic females to develop as men or for genetic males to develop as women. Sex determination is a complex process that can go awry at various stages of early development.
XY female and XX male sex reversals occur in about one in 20,000 live births.
Less complete sex reversals, known as disorders of sexual development (DSDs), are partial mismatches between genetic sex and the "secondary" sexual characteristics that give a person the appearance of being male or female.
DSDs occur in at least one in 100 births. These often result in "relatively mild forms" such as hypospadias, where the male urethra emerges from the underside of the penis, note Edwina Sutton and colleagues of the University of Adelaide, Australia, in the January issue of the Journal of Clinical Investigation.
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