Practical management of the intersex infant

Intersex occurs when the appearance of the internal or external genitalia is at variance with normal development for either sex. The first question asked by, and of new parents in relation to their offspring is often "Is it a boy or a girl"? A rational approach, based on knowledge of normal prenatal sexual development, and based on a careful physical examination to guide further investigation, is required to reach a diagnosis. We briefly review prenatal sexual development to provide a background to the assessment of genital ambiguity in the newborn. Aspects of physical examination are discussed in detail, with reference to published normative data where possible. We provide a classification of genital ambiguity and an approach to differential diagnosis. We highlight some of the many syndromes associated with genital ambiguity, with reference to their genetic basis where possible. In 46,XX individuals, the commonest cause of genital ambiguity is congenital adrenal hyperplasia due to 21-hydroxylase deficiency; however, in 46,XY individuals the differential diagnosis is wide, and may remain unexplained, even after extensive investigation. Two algorithms are presented, one of which provides an initial approach based on the presence of a uterus and palpable gonads alone, and a second illustrating a comprehensive differential diagnosis of the undervirilised 46,XY individual. We discuss our approach to sharing information on the diagnosis and management with the parents and highlight the early involvement of an experienced multidisciplinary team. Finally, we consider current controversial issues relating to gender assignment and management of genital ambiguity.