title: Prenatal diagnosis and treatment of 11beta-hydroxylase deficiency congenital adrenal hyperplasia resulting in normal female genitalia.
abstract: Congenital adrenal hyperplasia (CAH) consists of autosomal recessive disorders of cortisol biosynthesis, which in the majority of cases result from 21-hydroxylase deficiency. Another enzymatic defect causing CAH is 11beta-hydroxylase deficiency. In both forms, the resulting excessive androgen secretion causes genital virilization of the female fetus. For over 10 yr female fetuses affected with 21-hydroxylase deficiency have been safely and successfully prenatally treated with dexamethasone. We report here the first successful prenatal treatment with dexamethasone of an affected female with 11beta-hydroxylase deficiency CAH. The family had two girls affected with 1beta-hydroxylase deficiency born with severe ambiguous genitalia who were both homozygous for the T318M mutation in the CYP11B1 gene, which codes for the 11beta-hydroxylase enzyme. In the third pregnancy in this family, the female fetus was treated in utero by administering dexamethasone to the mother, starting at 5 weeks gestation. The treatment was successful, as the newborn 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 (R394delta1) in the CYP11B1 gene in this family.
authors.affiliation: Department of Pediatrics, Weill Medical College of Cornell University, New York, New York 10021, USA.
authors.forename: B I
authors.initials: BI
authors.lastname: Cerame
authors.forename: R S
authors.initials: RS
authors.lastname: Newfield
authors.forename: L
authors.initials: L
authors.lastname: Pascoe
authors.forename: K M
authors.initials: KM
authors.lastname: Curnow
authors.forename: S
authors.initials: S
authors.lastname: Nimkarn
authors.forename: T F
authors.initials: TF
authors.lastname: Roe
authors.forename: M I
authors.initials: MI
authors.lastname: New
authors.forename: R C
authors.initials: RC
authors.lastname: Wilson
mesh_terms: D000312:Adrenal Hyperplasia, Congenital / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics; D015193:Chorionic Villi Sampling; D003241:Consanguinity; D004252:DNA Mutational Analysis; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D005865:Gestational Age; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008431:Maternal-Fetal Exchange; D020125:Mutation, Missense; D010375:Pedigree; D011247:Pregnancy; D011296:Prenatal Diagnosis; D013252:Steroid 11-beta-Hydroxylase / Q000235:genetics; D014770:Virilism / Q000196:embryology / Q000209:etiology / Q000517:prevention & control*
chemical_list: D005938:Glucocorticoids; D003907:Dexamethasone; D013252:Steroid 11-beta-Hydroxylase