Show Summary Details
Page of

Normal and abnormal sexual differentiation 

Normal and abnormal sexual differentiation
Normal and abnormal sexual differentiation

I.A. Hughes

A newer version of this chapter is available. Latest version
A more recent version of this content exists; this version was replaced on 30 Nov 2011. The version that replaced it can be found here.
Page of

PRINTED FROM OXFORD MEDICINE ONLINE ( © Oxford University Press, 2015. All Rights Reserved. Under the terms of the licence agreement, an individual user may print out a PDF of a single chapter of a title in Oxford Medicine Online for personal use (for details see Privacy Policy).

date: 21 February 2018

Human sex development follows an orderly sequence of embryological events coordinated by a cascade of gene expression and hormone production in a time- and concentration-dependent manner. Underpinning the entire process of fetal sex development is the simple mantra: sex chromosomes (XX or XY) dictate the gonadotype (ovary or testis), which then dictates the somatotype (female or male phenotype).

The constitutive sex in fetal development is female. Male development to form a testis from the indifferent gonad (sex determination) and the internal and external phenotype (sex differentiation) is due to (1) testis-determining genes, in particular SRY (sex chromosome related gene on the Y chromosome), which is first expressed in the XY gonad at 6 to 7 weeks of gestation; and (2) production by the testis of (a) antimullerian hormone—to repress mullerian ducts forming the uterus and fallopian tubes, (b) androgens (testosterone and dihydrotestosterone)—to stabilize the Wolffian ducts; and (c) insulin-like factor 3 (INSL3)—required for the migration of the testis from the urogenital ridge to its site at birth within the scrotum. An understanding of these basic principles is essential to formulate a logical approach to the diagnosis of disorders of sex development.

Disorders of sex development (DSD)—these can be classified into three broad categories based on the knowledge of the karyotype: (1) sex chromosome abnormality—e.g. XO/XY, mixed gonadal dysgenesis; (2) XX DSD—e.g. congenital adrenal hyperplasia (see Chapter 13.7.2); (3) XY DSD—e.g. partial androgen insensitivity syndrome.

Clinical features—the commonest presentations of DSD are (1) ambiguous genitalia of the newborn; and (2) development of secondary sexual characteristics at puberty discordant with the sex of rearing—generally signs of virilization occurring in a child hitherto assumed to be female.

Investigation and management—an extensive repertoire is available, but the choice of genetic, endocrine, and imaging tests should be based on the DSD classification (determined by sex chromosome analysis by fluorescent in situ hybridization (FISH) using X centromeric and SRY probes, followed by full karyotyping) and aimed at reaching a consensus about the choice of sex assignment. Any surgical procedure required to alter the external phenotype consonant with sex assignment need not be undertaken urgently. It is essential that families of children with DSD have the benefit of support and counselling by a multidisciplinary team that comprises at a minimum an endocrinologist, urologist/gynaecologist, geneticist, and psychologist.

Access to the complete content on Oxford Medicine Online requires a subscription or purchase. Public users are able to search the site and view the abstracts for each book and chapter without a subscription.

Please subscribe or login to access full text content.

If you have purchased a print title that contains an access token, please see the token for information about how to register your code.

For questions on access or troubleshooting, please check our FAQs, and if you can't find the answer there, please contact us.