Bilateral breast nodules as an unusual manifestation of 17α-hydroxylase/17,20-lyase deficiency.

Introduction: 17α-hydroxylase/17,20-lyase deficiency (17-OHD) typically presents with sexual infantilism, hypertension, and hypokalemia. However, phenotypic variability, particularly breast development, may obscure diagnosis. This study aims to characterize an atypical presentation of 17-OHD with preserved breast development and breast nodules, and to evaluate clinical and hormonal features associated with breast development through a systematic literature review. Methods: A 38-year-old woman with bilateral breast nodules and ductal ectasia was diagnosed with 17-OHD, confirmed by Results: The patient exhibited classic signs of 17-OHD including hypertension, hypokalemia, adrenal hyperplasia, and hypogonadism, but also presented with atypical bilateral breast nodules and mammary duct ectasia. Hormone therapy resulted in clinical improvement and regression of the breast findings. Literature analysis of 43 patients with breast development showed that patients with 46,XX were diagnosed later than 46,XY (29.5 ± 11.5 vs. 19.8 ± 6.9 years, Conclusion: This case broadens the phenotypic spectrum of 17-OHD, highlighting that preserved breast development and benign breast lesions may delay diagnosis. Literature review suggests partial loss-of-function variants contribute to this phenotype. Greater awareness is essential to prevent misdiagnosis and unnecessary interventions.