Prenatal diagnosis and treatment of 11 beta-hydroxylase deficiency congenital adrenal hyperplasia resulting in normal female genitalia

Congenital adrenal hyperplasia (CAH) consists of autosomal recessive disord ers of cortisol biosynthesis, which in the majority of cases result from al -hydroxylase deficiency. Another enzymatic defect causing CAH is 11 beta-hy droxylase deficiency. In both forms, the resulting excessive androgen secre tion causes genital virilization of the female fetus. For over 10 yr female fetuses affected with 21-hydroxylase deficiency have been safely and succe ssfully prenatally treated with dexamethasone. We report here the first suc cessful prenatal treatment with dexamethasone of an affected female with 11 beta-hydroxylase deficiency CAH. The family had two girls affected with 11 beta-hydroxylase deficiency born with severe ambiguous genitalia who were both homozygous for the T318M mutation in the CYP11B1 gene, which codes for the 11 beta-hydroxylase enzyme. In the third pregnancy in this family, the female fetus was treated in utero by administering dexamethasone to the mo ther, starting at 5 weeks gestation. The treatment was successful, as the n ewborn was not virilized and had normal female external genitalia. A second family with two affected sons was also studied in preparation for a future pregnancy. We report a novel 1-bp deletion in codon 394 (R394 Delta 1) in the CYP11B1 gene in this family.