Sex determination and differentiation

A baby’s sex––one of its primary identifying features—is usually decided on the basis of a very brief inspection of the external genitalia completed by the birth attendant in the space of a few seconds. If there is a penis, the baby is declared to be a boy. If, instead, there is no penis and the genital folds are separated by a cleft, it is a girl. Recognizing the difference between male and female is easy when appearances are absolutely typical. Once in every 4500 births, however, it is impossible to say whether the baby is a boy or a girl because the genitalia are quite atypical or, in other words, ambiguous (1). In other cases, the external genitalia appear male or female, but the child is subsequently discovered, perhaps in the course of investigating or treating an inguinal hernia, to have internal anatomy normally associated with the opposite sex. For example, a female (with complete androgen insensitivity) can be born with testes and a male (with persistent Müllerian duct syndrome) can be born with fallopian tubes and a uterus. Other children are born with incompletely differentiated gonads that are neither typical testes nor ovaries; and may even contain elements of both, termed ovotestes. Chromosomes are no certain guide to sex either, as one in every 250 people has a major variation in the number of sex chromosomes (2). It is also possible to be chimeric, for example, 46,XX/46,XY.