Rare types of congenital adrenal hyperplasia: report of five children with 11β-hydroxylase deficiency including pathogenic and novel CYP11B1 variants.

11β-hydroxylasedeficiency (11β-OHD) is a rare form of congenital adrenal hyperplasia caused by biallelic pathogenic variants in the CYP11B1 gene. It leads to impaired cortisol synthesis, resulting in increased adrenocorticotropic hormone stimulation and consequent accumulation of steroid precursors, which are diverted to androgen synthesis. In addition, the accumulation of 11-deoxycorticosterone, which is a potent mineralocorticoid, causes hyporeninemic hypokalemic hypertension. We report the clinical, hormonal, and genetic profiles of five children with 11β-OHD, emphasising phenotypic variability, a median 2-year diagnostic delay, the crucial role of hormonal profile in diagnosis, and management challenges, including post-treatment central precocious puberty. Two novel CYP11B1 variants were identified in two unrelated patients. Hydrocortisone replacement resolved hypertension in only one of the three hypertensive patients; others required spironolactone. Early differentiation of 11β-OHD from 21-hydroxylase deficiency is critical to prevent hypertension-related morbidity.