Early prenatal diagnosis of 21‐hydroxylase deficiency using amniotic fluid 17‐hydroxyprogesterone determination and DNA probes

Abstract

The results of early prenatal diagnoses of congenital adrenal hyperplasia are reported. The determination of 17-hydroxyprogesterone values in amniotic fluid taken transabdominally at 11 weeks of gestation enabled prenatal diagnosis of congenital adrenal hyperplasia due to 21-hydroxylase (21-OH) deficiency. There is a clear-cut difference between normal and pathological values at that time of pregnancy. This method of diagnosis can be combined with genotyping of the fetus by HLA-DNA probes on chorionic villus sampling or can be used alone. Prenatal diagnosis with a 21-OH probe is possible when a preliminary study has demonstrated that the index case is homozygous for the deletion.

Screening of CYP21 gene mutations in 129 French patients affected by steroid 21-hydroxylase deficiency

“…Our results show that characterization of CAH mutations for prenatal diagnosis or carrier detection remains difficult because many mutations must be tested. Linked genetic markers, HLA, but also duplications and deletions of CYP2lP or C4 genes, as well as some polymorphisms on CYP21, may be used to follow the segregation of CAH alleles in families with an index case (Mornet et al, 1986b;Raux-Demay et al, 1989; and our unpublished results). More inclusive strategies such as DGGE or SSCP may lead to the characterization of most, but not all, of the mutations, as it seems that some mutations or polymorphisms may be undetected by these methodologies (FQec et al, 1992;Hayashi and Yandell, 1993).…”

The Molecular Basis of 21-Hydroxylase Deficiency

“…Measurement of 17-hydroxyprogesterone in amniotic fluid can accurately identify fetuses affected with classical CAH. 12,13 The initial determinations were made at 16 weeks' gestation. 12 More recently, first trimester amniocentesis has been performed, enabling early diagnosis by hormone measurement.…”

“…12 More recently, first trimester amniocentesis has been performed, enabling early diagnosis by hormone measurement. 13 Fetal adrenal glands are functional during the first trimester. Thus, maternal steroid treatment must be started by the fifth to seventh gestational weeks in order to suppress fetal adrenal androgen overproduction and prevent masculinization of affected female fetuses.…”