Delayed onset of puberty due to 17-alpha-hydroxylase deficiency, an atypical form of congenital adrenal hyperplasia

Objectives Delayed onset of puberty is a frequent referral to the paediatric gynaecologist. Although constitutional delay is the most common etiology, rare genetic conditions can be identified beginning with a simple workup. Methods We will review the case of a 16yo patient with a rare form for congenital adrenal hyperplasia (CAH). Results Our patient\u0027s first contact with paediatric gynaecology was at age 13 when she was seen for delayed puberty. Her medical issues included hypertension, hypokalemia and low cortisol. Workup identified an 46, XY karyotype, elevated follicle-stimulating hormone and luteinizing hormones, and undetectable sex hormones levels. Imaging did not identify any internal female organs. Further investigation through Medical Genetics identified a homozygous pathogenic variant c.1435 This mutation presents as 17-alpha-hydroxylase deficiency, an atypical form of CAH. Following diagnosis, the patient\u0027s maternal aunt disclosed a diagnosis of germ cell tumour requiring surgery and ultimately was found to carry the same genetic variant. At age sixteen, our patient chose to proceed with removal of gonads. Final pathology showed grossly abnormal testes, measuring half the normal volume. There was complete absence of Leydig cells in the testicular stroma. Conclusions The mutation leading to our patient\u0027s 17-alpha-hydroxylase deficiency has previously been identified within the Canadian Mennonite population. In this case, the patient\u0027s family member had hidden her diagnosis.Disorders of sexual differentiation are uncommon but important to consider when seeing patients for delayed onset of puberty. This case highlights the importance of a thorough family history, especially in the context of a rare condition.