Ambiguous Genitalia

Ambiguous genitalia, now more often called atypical genitalia or differences of sex development (DSD), is an uncommon congenital disease affecting roughly 1 in 2,000 babies, in which external genitalia do not seem normally male or female. The disorder occurs when biological sex chromosomes and external genitalia don’t match due to disturbances in foetal development.

In the first weeks of foetal development, gonadal tissue is undifferentiated until about the sixth week, when it is the chromosomes and hormones that determine whether testes or ovaries will develop. The most common cause is congenital adrenal hyperplasia (CAH), occurring in 1 in 15,000 live births, where an enzyme deficiency causes excess male hormone production that masculinises genetically female foetuses. 90% of instances of CAH are due to a lack of the enzyme 21-hydroxylase, which leads to increased androgen synthesis.

Other causes can be androgen insensitivity syndrome (genetic males do not respond to testosterone), 5-alpha-reductase deficiency, chromosomal abnormalities (such as mosaic karyotypes), or maternal hormones during pregnancy.
Females may have ambiguous genitalia with clitoral hypertrophy and labial fusion. Males may have a small penis and undescended testes. The treatment involves a multidisciplinary team of endocrinologists and urologists and includes life-sustaining hormone replacement therapy with cortisol and aldosterone and possible reconstructive surgery that is decided on a case-by-case basis with families.