Disorders of sex development (DSD) are a group of conditions where the development of chromosomal, gonadal or anatomical sex is atypical. Individuals may present with a blend of male and female characteristics, for example a baby with ambiguous genitalia at birth or an adolescent girl with primary amenorrhoea who on investigation is found to have an XY karyotype. The term ‘DSD’ is a recently adopted classification, which replaces the older terms of ‘intersex, hermaphroditism, pseudohermaphroditism and sex reversal’. This older nomenclature is confusing to clinicians and can be felt as pejorative by patients.

The prosaic definition of ‘sex’ is: ‘a species dimorphism, represented at different planes by chromosomes and the genes they carry, gonads, sex ducts, external genitalia, bodily habitus, secondary sex characters and behaviour or psychological attitudes’. ‘Phenotypic sex’ is the apparent sex, judged by external characteristics. Older terms no longer in regular use, include: ‘gonadal sex’, referring to whether there is a testes or ovary present and ‘karyotypic sex’, referring to the chromosome status. ‘Sexual orientation’ refers to the direction of erotic interest, and ‘gender identity’ refers to a person’s self-representation as male or female. Psychosexual development is highly complex and is influenced by many factors, including chromosomes, pre- and postnatal exposure to hormones and brain structure, as well as social influences and family dynamics.

Causes of gender identity disorder or gender dissatisfaction in the absence of atypical sex development are not discussed in this chapter.

1. In the normal fetus, the chromosomal complement of the zygote determines whether the gonad becomes a testis or ovary. The first step in the pathway to a male or female phenotype is dependent on the SRY gene (sex-determining region of the Y chromosome). This gene, helped by other testes-determining genes, causes the gonad to begin development into a testis.

2. Ovarian development was in the past considered a ‘default’ development due solely to the absence of SRY; however, recently, ovarian-determining genes have also been found.

3. All fetuses have Müllerian and Wolffian ducts and the potential to develop male or female internal and external genitalia.

4. This process can go wrong at any stage, leading to the birth of a baby with a DSD.

5. DSD can be diagnosed at birth but can also present at adolescence.

6. All babies should be assigned to a sex of rearing. In the presence of a DSD, this is decided by the parent and a multidisciplinary specialized team. Birth registration can be delayed until agreement is reached.

7. Medical management includes genital surgery to reinforce the chosen sex of rearing, but this is a controversial and topical issue.

It has long been known that the short arm of the Y chromosome controls testicular development, but identification of the gene has proved a long task. Studies were based on cases in which the gonads and other sex features were contrary to the chromosomes, so-called ‘sex reversal’. It is now clear that a gene called SRY (sex-determining region of Y) is responsible. It encodes a DNA-binding protein, which probably influences other genes to produce differentiation of the primitive gonadal streak into testis. The detail of SRY’s mode of action is now the focus of attention. A very few XX males do not have SRY, so some other genetic material must, in certain circumstances, be able to induce testicular differentiation.