Fetal Smith-Lemli-Opitz syndrome can be detected accurately and reliably by measuring amniotic fluid dehydrocholesterols

The Smith–Lemli–Opitz syndrome, characterized by limb, face and organ abnormalities, and mental retardation, is caused by an inherited block in the step of cholesterol biosynthesis in which the Δ7 double bond of 7-dehydrocholesterol is reduced. It is diagnosed by the presence of markedly elevated levels of 7-dehydrocholesterol and 8-dehydrocholesterol in plasma and tissue. We measured amniotic fluid sterols in 15 pregnancies in 13 women who had previously carried an affected fetus. Cholesterol, 7–dehydrocholesterol and 8-dehydrocholesterol concentrations averaged 18±3, 9·8±2·9 and 5·0±1·7 μg/ml, respectively, in seven pregnancies with an affected fetus or child. In contrast, these levels were 19±3, 0·05±0·01 and <0·005 μg/ml, respectively, in eight increasedrisk pregnancies with normal outcomes and 16±2, 0·07±0·01 and <0·005 μg/ml in normal controls. 7-dehydrocholesterol concentrations, 2·2–26 and 0·05–0·10 μg/ml in pregnancies with an affected and unaffected fetus, respectively, did not overlap. Thus, abnormally elevated amniotic fluid dehydrocholesterol concentrations are an accurate predictor of fetal Smith–Lemli–Opitz syndrome. A false-positive or a false-negative result is highly unlikely. © 1998 John Wiley & Sons, Ltd.