Understanding the genetic aetiology in patients with XY DSD

Abstract

Background: Disorders of sex development (DSD) consist of a wide range of disorders and are commoner in those with an XY karyotype. In over half of these cases who have a 46,XY karyotype and who are raised as boys, the underlying aetiology remains unclear.

Areas of agreement: Identification of the underlying genetic abnormality may predict long-term outcome. However, genetic abnormalities that are associated with XY DSD manifest themselves with a wide range of phenotype. To understand the aetiology as well as the phenotypic variation, there is a need to harness the advanced genetic technology that is now available.

Areas of controversy: The point at which genetic analysis should be undertaken in the course of investigations is unclear. In addition, there is little agreement on the most effective approach for genetic analysis that will be of clinical benefit to the patient.

Areas timely for developing research: There is a need to understand and improve the clinical utility of genetic analysis in the clinical setting of the patient with a suspected DSD. This will be even more important when parallel gene sequencing identifies variations in multiple genes.

Keywords: genes; gonad development; karyotype; sex development.