Context: Disorders of sex development (DSDs) may arise from genetic defects in testis or ovary determination. Current analytical technologies and improved understanding of major regulatory pathways have cast new insight into the genetic basis for these disorders.
Evidence acquisition: A PubMed search was performed for the years 2011-13 using the terms "disorder of sex development," "gonadal dysgenesis," "ovarian dysgenesis," "array CGH," and "whole exome sequencing." Only articles from peer-reviewed journals were included.
Evidence synthesis: Key themes that emerged included aberrant regulation of SOX9 via the hTES promoter in 46,XY gonadal DSDs, the role of the MAPK pathway in normal and aberrant gonadal development, and the role of new technologies in identification of gonadal DSDs.
Conclusions: With the advent of the robust new technologies of array comparative genomic hybridization and genomic sequencing in recent years, many new sex-determining genes have been identified. These genes have been organized into ovarian- and testicular-determining pathways that can block each other's activities. Identification of a mutation in a sex-determining gene in an individual affected with a DSD may warrant more extensive investigation for other phenotypic effects as well as genetic testing of other family members.