Genetic Variants in SRD5A2 in a Spectrum of DSD Patients from Australian Clinics Highlight Importance of Genetic Testing alongside Typical First-Line Investigations

Introduction: Steroid 5-alpha reductase deficiency (5 alpha-R2D) is a rare condition caused by genetic variants that reduce the activity of the enzyme that converts testosterone into dihydrotestosterone. The clinical spectrum of 5 alpha-R2D is known to overlap with other 46,XY differences of sex development (DSD) such as androgen insensitivity or gonadal dysgenesis. However, the clinical trajectories of the aetiologies can differ, with 5 alpha-R2D presenting its own challenges. Methods: In this study, we have collated clinical information for five individuals with variants in SRD5A2 identified using research genetic testing in an Australian paediatric setting. Results: We describe how a genetic finding resolved or confirmed a diagnosis for these individuals and how it guided clinical management and family counselling. Conclusion: This work highlights the importance of early genetic testing in children born with 46,XY DSD where it complements traditional first-line testing.