GENETICS: Edited by Nathaniel H. RobinGenetics of human sexual development and related disordersMartinez de LaPiscina, Idoiaa,b,c; Flück, Christa E.a,b Author Information aDivision of Pediatric Endocrinology, Diabetology and Metabolism, Department of Pediatrics, Inselspital, Bern University Hospital bDepartment of Biomedical Research, University of Bern, Bern, Switzerland cBiocruces Bizkaia Health Research Institute, Cruces University Hospital, UPV/EHU, CIBERER, CIBERDEM, ENDO-ERN, Barakaldo, Spain Correspondence to Christa E. Flück, MD, Pediatric Endocrinology, Diabetology and Metabolism, Department of Pediatrics, and Department of BioMedical Research (DBMR), Inselspital, Bern University Hospital, Freiburgstrasse 15/C845, 3010 Bern, Switzerland. Tel: +41316320499; e-mail: [email protected] Current Opinion in Pediatrics: December 2021 - Volume 33 - Issue 6 - p 556-563 doi: 10.1097/MOP.0000000000001066 Buy Metrics Abstract Purpose of review The aim of this study was to provide a basic overview on human sex development with a focus on involved genes and pathways, and also to discuss recent advances in the molecular diagnostic approaches applied to clinical workup of individuals with a difference/disorder of sex development (DSD). Recent findings Rapid developments in genetic technologies and bioinformatics analyses have helped to identify novel genes and genomic pathways associated with sex development, and have improved diagnostic algorithms to integrate clinical, hormonal and genetic data. Recently, massive parallel sequencing approaches revealed that the phenotype of some DSDs might be only explained by oligogenic inheritance. Summary Typical sex development relies on very complex biological events, which involve specific interactions of a large number of genes and pathways in a defined spatiotemporal sequence. Any perturbation in these genetic and hormonal processes may result in atypical sex development leading to a wide range of DSDs in humans. Despite the huge progress in the understanding of molecular mechanisms underlying DSDs in recent years, in less than 50% of DSD individuals, the genetic cause is currently solved at the molecular level. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.