Severe Hyperandrogenism Revealing a 46,XY Disorder of Sex Development Due to a Novel NR5A1 Mutation

46,XY disorders of sex development (DSDs) are rare congenital conditions resulting from impaired gonadal differentiation and/or steroidogenesis. The NR5A1 gene encodes steroidogenic factor 1 (SF-1), a key regulator of gonadal development and endocrine function, and pathogenic variants are associated with a broad phenotypic spectrum that may present beyond the neonatal period. We report the case of a 12-year-and-6-month-old phenotypic female adolescent presenting with severe hirsutism, acne, primary amenorrhea, and progressive virilization. Hormonal evaluation demonstrated hyperandrogenism with hypergonadotropic hypogonadism. Imaging revealed the absence of a normal uterus and ovaries, with the presence of a Müllerian remnant, along with bilateral gonadal structures consistent with testicular tissue, and cytogenetic analysis showed a 46,XY karyotype. Genetic testing identified a novel heterozygous pathogenic NR5A1 splice-site variant (c.871-2A>G), confirming the diagnosis of 46,XY DSD. Multidisciplinary management included bilateral gonadectomy followed by estrogen replacement therapy. This case highlights an uncommon adolescent presentation of 46,XY DSD revealed by severe hyperandrogenism in a phenotypic female individual and underscores the importance of molecular genetic testing for accurate diagnosis, management, and long-term follow-up.