Disorders of sex development

Infants born with ambiguous genitalia represent a complex clinical challenge. A systematic clinical investigation aims at determining the hormone production and which anatomical structures are present in order to understand at what level the sex differentiation has been affected; chromosomal, gonadal or hormonal synthesis and action levels. The increased genetic knowledge in the field has opened up new diagnostic possibilities. Sex development requires the balanced and sequential activation of transcription factors, signaling molecules and hormones. It has recently been shown that not only testis but also normal ovarian development is an active process. Genes involved in gonadal disorders of sex development often act in a gene dosage-dependent manner, with different effects in XY or XX embryos. The management of patients with disorders of sex development, including decisions about sex of rearing, must be carried out by a specialized multidisciplinary team and include an extended genetic investigation as well as psychological considerations.