An evaluation of cases of disorders of sex development related to SRD5A2

Pathogenic variants in SRD5A2 are a common cause of 46,XY disorders of sex development (DSDs). The aim of this study is to present the clinical, laboratory, and genetic characteristics of patients diagnosed with SRD5A2-associated 46,XY disorders of sex development (DSD), along with any decisions made regarding sex assignment. Furthermore, it also highlights the challenges encountered in sex assignment and the potential influence of social factors on how families adapt to these decisions.

This retrospective, single-center study analyzed 29 DSD cases with 46,XY karyotypes, all of which were found to carry SRD5A2 variants.

The majority of the patients initially presented with female sex assignment (86.2%). The study identified a predominance of homozygous SRD5A2 variants (93.1%) with the most common variant being p.Ala65Pro. Gender assignment decisions were made for 25 cases, with male gender assignment in 80% of cases. The parents of three adolescent athlete patients did not comply with the male gender decision and one of these patients was supported as a girl after the age of 18, with a corrective operation being subsequently performed. No patients underwent a gonadectomy before the age of 18.

This study emphasizes the challenges in sex assignment for SRD5A2-associated DSD. Some XY DSD patients may have difficulty adhering to medical team guidance because of the negative impact of the patients in their families. When necessary, gender assessment committees should reevaluate DSD cases from a current perspective and reconsider their decisions.