SMITH-LEMLI-OPITZ SYNDROME - PRENATAL-DIAGNOSIS BY QUANTIFICATION OF CHOLESTEROL PRECURSORS IN AMNIOTIC-FLUID

Until recently, the diagnosis of Smith-Lemli-Opitz syndrome (SLOS), an autosomal recessive malformation/mental retardation syndrome, was mad e on the basis of clinical criteria alone. As a result, prenatal diagn osis has been possible only if sonography disclosed distinct fetal mal formations in a subsequent pregnancy. However, the recent description of increased levels of 7-dehydrocholesterol (cholesta-5,7-dien-3 beta- ol) in patients with SLOS, most likely caused by a deficiency of 3 bet a-hydroxysteroid-Delta(7)-reductase, has provided an apparently reliab le biochemical marker for diagnosis of SLOS. To determine if this abno rmality of sterol metabolism has utility for prenatal diagnosis of SLO S, we measured the levels of neutral sterols in stored amniotic fluid samples from two SLOS pregnancies. In both cases, the diagnosis of SLO S was made in the neonatal period by clinical criteria and the finding of markedly increased levels of 7-dehydrocholesterol in plasma. Quant itative analysis by gas chromatography of sterols extracted from the a mniotic fluid of both pregnancies revealed similar, markedly increased levels of 7-dehydrocholesterol and its precursor, lathosterol (choles t-7-en-3 beta-ol), both of which were undetectable in reference amniot ic fluids. These findings suggest that abnormalities of cholesterol bi osynthesis in SLOS may be sufficiently expressed in fetal life to perm it prenatal diagnosis of this disorder by measurement of 7-dehydrochol esterol in amniotic fluid. (C) 1995 Wiley-Liss, Inc.