EP1808 - LBA_ECE_1094 - Familial 11β-hydroxylase deficiency associated with a CYP11B1 mutation: phenotypic variability across two generations, including a severe form with salt-wasting syndrome

Abstract

11β-hydroxylase deficiency is an autosomal form of congenital adrenal hyperplasia, accounting for 5%-8% of cases. It results in impaired cortisol synthesis, leading to an accumulation of precursors that causes hyperandrogenism and, in some cases, hypertension. This study describes the clinical, biological, and progressive characteristics of a familial deficiency observed in three sisters born to an affected mother. A retrospective descriptive study conducted in the pediatric endocrinology department at Hassan II University Hospital in Fez. Clinical, laboratory, genetic, therapeutic, and follow-up data for the patients were collected from their medical records. Patient 1 (14 years old): neonatal sexual differentiation disorder with testosterone 2.5 ng/mL, 17-OHprogesterone 12 ng/mL, Δ4-androstenedione 17 ng/mL, 11-deoxycortisol 24 ng/mL, cortisol 2.8 µg/dl, ACTH 95 pg/mL, hyponatremia, normal serum potassium. CYP11B1 mutation confirmed. Started on hydrocortisone at birth, vaginoplasty at age 3. Course marked by poor compliance, melanoderma, and episodes of hyponatremia, with advanced bone age. Patient 2 (10 years old): similar neonatal presentation, identical CYP11B1 mutation. Early replacement therapy and corrective surgery. Favorable outcome without melanoderma, initial short stature and low weight with gradual catch-up. Patient 3: comparable neonatal presentation but with hyponatremia and hyperkalemia; identical mutation. Death at age 1 due to salt-wasting syndrome. All three patients are daughters of an asymptomatic mother who was diagnosed secondarily after her daughters were diagnosed with 11β-hydroxylase deficiency and placed on hydrocortisone. Two other daughters, treated with antenatal dexamethasone (SRY-negative), had a favorable outcome. This case illustrates the phenotypic variability of a CYP11B1 mutation within the same family, ranging from a compensated form to severe salt-wasting disease. It underscores the importance of family screening, genetic counseling, and strict adherence to treatment to prevent progressive complications.