Ambiguous genitalia in neonates

Ambiguous genitalia (i.e., a genital phenotype that is neither clearly male nor female) are caused by the atypical development of chromosomal, gonadal, or anatomical sex. The complex group of disorders that cause ambiguous genitalia are called disorders of sex development (DSD).

DSD are congenital conditions that most commonly present in the newborn period.

DSD can be classified as sex chromosome DSD, 46,XY DSD, or 46,XX DSD .

Sex chromosome DSD results from the atypical complement of sex chromosomes, and includes syndromes such as Turner syndrome (45,X with one absent sex chromosome) and Klinefelter syndrome (XXY with one additional X chromosome). Mosaicism occurs when more than one type of chromosomal arrangement is present (e.g., 45,X/46, XY).

46,XX DSD are conditions characterised by excess exposure to androgens. Over 95% of causes of ambiguous genitalia with a 46,XX genotype are due to congenital adrenal hyperplasia secondary to 21 hydroxylase deficiency.

46,XY DSD can be due to several aetiologies and usually requires a more extensive diagnostic evaluation.

The initial management of a neonate with ambiguous genitalia is a social and clinical emergency. The local team has a key role in coordinating the initial assessment and investigations, and supporting parents. It is important there is early discussion with a more specialist multidisciplinary team with expertise in paediatric endocrinology, genetics, and surgery, and with appropriate psychiatric/psychological support. For many DSDs, long-term surgical and psychosexual outcomes remain uncertain.

Disorders of sex development (DSD) are congenital conditions in which development of chromosomal, gonadal, or anatomical sex is atypical.[1]Lee PA, Nordenström A, Houk CP, et al. Global disorders of sex development update since 2006: perceptions, approach and care. Horm Res Paediatr. 2016 Jan 28;85(3):158-80. https://www.karger.com/Article/FullText/442975 http://www.ncbi.nlm.nih.gov/pubmed/26820577?tool=bestpractice.com A subset of children with DSD present at birth with ambiguous genitalia (i.e., a genital phenotype that is neither clearly male nor clearly female) and without other dysmorphic features. Many causes have a genetic basis. A very rare exception may occur when there is virilisation of a 46,XX fetus by maternal virilising tumours or maternal exposure to androgenic drugs.

This topic addresses the initial approach to neonates with ambiguous genitalia who are not identified as having a specific chromosomal syndrome in which ambiguous genitalia may be one of a number of presenting features.