11β-hydroxylase deficiency is the second most frequent cause of congenital adrenal hyperplasia (CAH), corresponding to approximately 5% of cases., and caused by inactivating mutations in the CYP11B1 gene. We aimed to describe four new cases from two different families with a clinical diagnosis of 11β-hydroxylase deficiency. Family 1: Two siblings born from consanguineous parents. A 31-year-old (yo) woman presented at 5 yo with genital ambiguity (Prader II), high blood pressure (HBP) and precocious pubarche (PP). She lost follow and returned after 3 full term normal pregnancies while using prednisone. 4 years after last gestation, she remained normotensive without any treatment. Her 24 yo brother presented at age 7 yo with PP, hypokalemia and HBP, when glucocorticoids and anti-hypertensives were started. He had low treatment adherence and evolved with persistent hypertension and left ventricular hypertrophy. Family 2: A 2.9 yo boy presented with PP and high BP, managed with hydrocortisone and anti-hypertensives. His sister presented at 21 days of life with genital ambiguity and salt wasting, managed with hydrocortisone and oral sodium. A detailed steroid profile was performed in all subjects, which confirmed the diagnosis. The CYP11B1 coding region of the patients and their parents was automatically sequenced. In the two siblings from Family 1, a homozygous splice site point mutation, IVS4 ds-1 G>A, was identified in exon 4 (g.3132G> A). In Family 2, both siblings harbored a nonsense mutation in exon 6 (c.1066 C> T), which generates a truncated protein (p.Q356X). The mutations presented herein were associated with a highly variable phenotype, from a mildly virilizing phenotype to a high degree of virilization with hypertension and with salt wasting, which is unexpected. Further studies of variants in other genes associated with hypertension, in compensatory pathways of steroid synthesis and metabolism, or the verification of chimeric CYP11B genes are needed to clarify the phenotypic heterogeneity.
20 - 23 May 2017
European Society of Endocrinology