Novel NR5A1 variants associated with hypospadias and disorders of sex development: A series case report of 4 patients

This case series expands the pathogenic landscape of NR5A1 and demonstrates its capacity to disrupt sexual development across diverse karyotypes (46,XY and 46,XX). Early genetic diagnosis enables accurate classification, informs surgical and endocrine decision-making, guides gonadoblastoma surveillance, and facilitates family counseling. NR5A1 should be included in first-tier genetic testing for children with unexplained hypospadias or DSD, especially when accompanied by biochemical evidence of primary gonadal failure.