Update on the genetics of differences of sex development (DSD)

Best Pract Res Clin Endocrinol Metab. 2019 Jun;33(3):101271. doi: 10.1016/j.beem.2019.04.005. Epub 2019 Apr 13.


Human gonadal development is regulated by the temporospatial expression of many different genes with critical dosage effects. Subsequent sex steroid hormone production requires several consecutive enzymatic steps and functional hormone receptors. Disruption of this complex process can result in atypical sex development and lead to conditions referred to as differences (disorders) of sex development (DSD). With the advent of massively parallel sequencing technologies, in silico protein modeling and innovative tools for the generation of animal models, new genes and pathways have been implicated in the pathogenesis of these conditions. Here, we provide an overview of the currently known DSD genes and mechanisms involved in the process of gonadal and phenotypical sex development and highlight phenotypic findings that may trigger further diagnostic investigations.

Keywords: developmental genetics; differences of sex development; gonadal dysgenesis; massively parallel sequencing; steroidogenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Disorders of Sex Development / genetics*
  • Female
  • Gonadal Steroid Hormones / biosynthesis
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Phenotype
  • Sex Determination Processes


  • Gonadal Steroid Hormones