[Prevention of sexual ambiguity in children with 21-hydroxylase deficiency by treatment in utero].
In the classical form of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, female fetuses are virilized by the excessive production of adrenal androgens. Sexual ambiguity is a major complication. Prenatal treatment has been proposed with the aim of reducing the adrenal androgen overproduction and hence of preventing the in utero virilization of CAH affected females. As there is good placental transfer of natural or synthetic glucocorticoids, dexamethasone (Dex) in particular, efficient treatment can be administered to the fetus via the mother. In early protocols the mothers were given 0.5 mg of Dex either 8- or 12 hourly. Analysis of the results of a French multicentric study has shown that the first consideration is to start treatment as early as possible, and no later than the 7th week of gestation. Also, the daily dose should be adjusted to maternal size. A dose of 20-25 micrograms/kg body weight is suggested. As this condition has to be treated early it is not possible to make a prenatal diagnosis before instituting therapy, which is not necessary in 7 out of 8 fetuses. It is thus important to establish as soon as possible a reliable diagnosis of sex and CAH. The generalization of villus chorionic biopsies and the recent progress in molecular genetics--restriction length fragment polymorphism and polymerase chain reaction (PCR)--now permit a direct analysis of the DNA during the first trimester. In particular, the determination of point mutations using PCR amplification of specific alleles in the proband an the parents, simplifies the procedure and also increases the reliability of prenatal diagnosis. On the whole, prenatal treatment with an adequate protocol has been fully or partially successful in almost all cases. No teratogenic or major adverse effects in the mother or child have been reported.
Forest
M G
MG
INSERM U 329, hôpital Debrousse, Lyon, France.
David
M
M
D000312:Adrenal Hyperplasia, Congenital / Q000209:etiology; D002648:Child; D003907:Dexamethasone / Q000627:therapeutic use*; D012734:Disorders of Sex Development / Q000209:etiology* / Q000517:prevention & control*; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis / Q000628:therapy*; D006801:Humans; D007231:Infant, Newborn; D008661:Metabolism, Inborn Errors / Q000150:complications* / Q000175:diagnosis; D011247:Pregnancy; D011296:Prenatal Diagnosis
D003907:Dexamethasone
Prévention de l'ambiguïté sexuelle des enfants atteints de déficit en 21-hydroxylase par traitement in utero.