Cytochrome P450 oxidoreductase (POR) deficiency is a disorder of steroidogenesis associated with a broad range of clinical presentations. Steroid abnormalities occur in all patients, consistent with a form of congenital adrenal hyperplasia (CAH) causing deficiencies of both 21-hydroxylase and 17a-hydroxylase/17,20-lyase; therefore, some patients with POR deficiency may have an abnormal newborn screen for 21-hydroxylase deficiency. Like classical CAH, the steroid abnormalities may lead to cortisol deficiency, which in some cases can be life-threatening without treatment. Disordered sex development can be observed in both males and females, and ambiguous genitalia is a common finding. At the severe end of the spectrum, patients may also have skeletal and craniofacial findings consistent with Antley-Bixler syndrome, including craniosynostosis, brachycephaly, severe midface hypoplasia, radiohumeral synostosis, and multiple joint contractures.