Gs. Tint et al., FETAL SMITH-LEMLI-OPITZ SYNDROME CAN BE DETECTED ACCURATELY AND RELIABLY BY MEASURING AMNIOTIC-FLUID DEHYDROCHOLESTEROLS, Prenatal diagnosis, 18(7), 1998, pp. 651-658
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.