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 Delta(7) double bond of 7-dehydrocholesterol is reduced. It is diagnosed by the presen ce of markedly elevated levels of 7-dehydrocholesterol and 8-dehydroch olesterol in plasma and tissue. We measured amniotic fluid sterols in 15 pregnancies in 13 women who had previously carried an affected fetu s. Cholesterol. 7-dehydrocholesterol and 8-dehydrocholesterol concentr ations averaged 18 +/- 3, 9.8 +/- 2.9 and 5.0 +/- 1.7 mu g/ml, respect ively, in seven pregnancies with an affected fetus or child. In contra st, these levels were 19 +/- 3, 0.05 +/- 0.01 and <0.005 mu g/ml, resp ectively, in eight increased risk pregnancies with normal outcomes and 16 +/- 2, 0.07 +/- 0.01 and <0.005 mu g/ml in normal controls. 7-dehy drocholesterol concentrations, 2.2-26 and 0.05-0.10 mu g/ml in pregnan cies with an affected and unaffected fetus, respectively, did not over lap. Thus, abnormally elevated amniotic fluid dehydrocholesterol conce ntrations are an accurate predictor of fetal Smith-Lemli-Opitz syndrom e. A false-positive or a false-negative result is highly unlikely. (C) 1998 John Wiley & Sons, Ltd.