Genetic control of typical and atypical sex development

In this Review, Reyes et al. provide an overview of the embryology and genetics of typical sex development, before discussing the clinical manifestations, genetic causes and phenotypic complexity of differences in sex development. Sex development relies on the sex-specific action of gene networks to differentiate the bipotential gonads of the growing fetus into testis or ovaries, followed by the differentiation of internal and external genitalia depending on the presence or absence of hormones. Differences in sex development (DSD) arise from congenital alterations during any of these processes, and are classified depending on sex chromosomal constitution as sex chromosome DSD, 46,XY DSD or 46,XX DSD. Understanding the genetics and embryology of typical and atypical sex development is essential for diagnosing, treating and managing DSD. Advances have been made in understanding the genetic causes of DSD over the past 10 years, especially for 46,XY DSD. Additional information is required to better understand ovarian and female development and to identify further genetic causes of 46,XX DSD, besides congenital adrenal hyperplasia. Ongoing research is focused on the discovery of further genes related to typical and atypical sex development and, therefore, on improving diagnosis of DSD.

Automated summary

In this review, the authors provide an overview of the embryology and genetics of typical sex development and discuss the clinical manifestations and genetic causes of differences in sex development. Sex development relies on gene networks and hormonal factors, and differences in sex development (DSD) can arise from congenital alterations during these processes. Understanding the genetics and embryology of sex development is essential for diagnosing and managing DSD, and advances have been made in understanding the genetic causes of DSD, especially for 46,XY DSD. Further research is needed to better understand 46,XX DSD and identify additional genetic causes.