46, XX DSD with Atypical Genitalia: Clinical Insights and Diagnostic Approaches

Congenital adrenal hyperplasia (CAH) is a rare disorder with autosomal recessive inheritance; it was historically known as adrenogenital syndrome. Patients with virilizing forms of CAH and a 46,XX karyotype present with varied degrees of hyperandrogenism due to different genetic defects in the adrenal steroidogenesis pathway. This comprehensive review describes a simplified diagnostic approach for patients with atypical genitalia and 46, XX DSD. It highlights the importance of a detailed history and clinical examination, with specific pointers toward the etiological diagnosis. There is a need for utilizing standardized liquid chromatography/tandem mass spectrometry (LC-MS/MS) assays to accurately diagnose these disorders of steroidogenesis. Choosing appropriate molecular testing methods has significant implications for establishing the diagnosis and providing genetic counseling.