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Congenital adrenal hyperplasia (CAH) owing to 21-hydroxylase deficiency is an autosomal recessive disorder caused by mutations in the CYP21A2 gene. Females affected with classical CAH are at risk for genital ambiguity, but can be treated in utero with dexamethasone before 9 gestational weeks to prevent virilization. Early genetic diagnosis is unavailable through current invasive methods of chorionic villus sampling and amniocentesis. New developments in prenatal genetic testing utilize fetal DNA extracted from maternal blood through noninvasive methods, which allow the determination of fetal gender and the diagnosis of CAH at an early gestational age (<9 weeks). Noninvasive prenatal diagnosis allows for the establishment of early and effective management plans in fetuses at risk for CAH and avoids unnecessary prenatal dexamethasone treatment., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Prenatal diagnosis of 21-hydroxylase deficiency, the most common cause of congenital adrenal hyperplasia (CAH), has benefited from the advances in endocrinologic and molecular genetic studies. In 1976, prenatal diagnosis of the disease was first attempted by measuring 17-hydroxyprogesterone in the amniotic fluid in the second trimester of pregnancy. Discovery of a close linkage between HLA and the disease gave a second approach for prenatal diagnosis, the latter being made by linkage study of the haplotypes of the index case in a given family. Diagnosis was later made directly by molecular biology. Currently, the studies of the C4-CYP21B gene locus by Southern blotting and the CYP21B gene mutations by PCR methods simplify the diagnostic procedure of an early and accurate prenatal diagnosis in the first trimester. In these conditions all families are now informative. Moreover, using a direct genetic analysis associated with the possibility of detecting the heterozygotes in a non-related CAH population, a prenatal diagnosis can be done in a family without a previously CAH affected child. From our results in a series of 274 pregnancies at risk for CAH in whom prenatal diagnosis has been made by these different approaches, it can be concluded that steroid analysis in the amniotic fluid is an accurate method but provides only a late (second trimester) diagnosis, while an early and accurate diagnosis now relies on adequate molecular genetic studies on chorion villus biopsies. In the aim to prevent the virilization of the external genitalia in CAH female fetuses, prenatal treatment was instituted in our group in 1979 by giving dexamethasone to the mother. This prenatal treatment appears safe for the fetus and the child and is effective in preventing virilization of CAH affected females. Although the degree of prevention is not always complete in all cases, the advantages of prenatal treatment are prevailing over the complications observed in a few mothers.