Difficult prenatal diagnosis in mild Smith‐Lemli‐Opitz syndrome

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder of cholesterol biosynthesis caused by mutations of the 7-dehydrocholesterol (7DHC) reductase gene (DHCR7). We present our experience with prenatal diagnosis of an affected fetus with a very mild form of SLOS. The mother underwent prenatal diagnosis by chorionic villus (CV) sampling at 11 2/7 weeks because of having two prior affected sons with SLOS. The 7DHC/total-sterol ratio in the fetus was higher than in normal control fetuses but lower than the ratio observed in CV of three other fetuses in whom SLOS was diagnosed prenatally. The pregnancy was terminated at 13 2/7 weeks. The level of 7DHC in amniotic fluid (AF) obtained at the time of pregnancy termination was unequivocally elevated, confirming the diagnosis of SLOS. This report illustrates the difficulties with the interpretation of biochemical prenatal diagnosis based on the determination of 7DHC/total-sterol ratio in CV sample in a case of mild SLOS, whereas biochemical testing of amniotic fluid clearly manifests the biochemical defects of SLOS as early as 13 weeks of gestation.