Ambiguous Genitalia and Disorders of Sexual Differentiation

The birth of an infant with ambiguous genitalia generates difficult multiple medical, surgical, ethical, psychosocial, and physical issues for patients and their parents. Phenotypic sex results from the differentiation of internal ducts and external genitalia under the influence of hormones and other additional factors. When discordance occurs among three processes (chromosomal, gonadal, phenotypic sex determination), a DSD is the result.  Terminology, such as hermaphrodite, pseudo-hermaphrodite, and intersex, are considered to be pejorative and dated. These terms have been replaced by the term disorders of sexual development (DSD) by the consensus statement on the management of intersex disorders. Disorders of sexual development are defined as congenital conditions characterized by atypical development of chromosomal, gonadal, or anatomic sex. Normal sexual development in utero is dependent upon a precise and coordinated spatiotemporal sequence of various activating and repressing factors. Any deviations from the usual pattern of differentiation can present as DSDs. Two distinct processes occur in normal sexual development. The first of which is sex determination, in which the bi-potential gonads are induced to form either the male testes or the female ovaries. Secondarily, the newly formed gonads secrete hormones to modulate the formation of internal and external genitalia. The phenotypic manifestation of DSDs are diverse and can include; bilateral undescended testes, severe hypospadias (scrotal or perineal), clitoromegaly, a fusion of posterior labial folds, female external genitalia with palpable gonad, discordant genitalia, and sex chromosomes. The inclusion of disorders in which there is no genital/gonadal discordance like Turner syndrome, Klinefelter syndrome, simple hypospadias remains controversial. Regardless of presentation or severity, individuals require an interprofessional approach that is warranted to improve the quality of life and achieve the best possible outcomes.