Abnormalities of sex determination and differentiation result from mutations of any of the genes involved in male or female sex development. Some of these mutations are well-established but additional mechanisms remain to be described (1). In addition to the adequate expression of these genes, proper timing of their expression is also important. For example, normal but delayed androgenic effects result in incomplete masculinization of genitalia while the persistent presence of Müllerian remnants results from normal but delayed MIS action.

For clinical purposes, DSDs in newborns are classified according to karyotype. Based on the various steps of sex differentiation and development, we suggest the following classification: (A) DSD with a 46,XY karyotype (formerly referred to as male pseudohermaphroditism, undervirilization of an XY male and undermasculinization of an XY male. In 46,XY DSD the bipotential gonads differentiate to variable degrees into testes), (B) DSD with a 46,XX karyotype (formerly referred to as female pseudohermaphroditism or masculinization of an XX female. In 46,XX DSD the bipotential gonads usually differentiate into ovaries but with abnormally increased androgen exposure and (C) DSD with an unusual karyotype such as mosaicism (45,XO/46,XY or 46,XX/46,XY), transposition of genes (46,XX, SRY+) or chromosome deletions that include one of the genes necessary for sex determination and differentiation (1).