First-trimester diagnosis of Smith-Lemli-Opitz syndrome

We report here the prenatal diagnosis of Smith-Lemli-Opitz (SLO) syndrome in the first trimester by direct measurement of 7-dehydrocholesterol (7-DHC) in a chorionic villus (CV) biopsy. The proband was diagnosed clinically at birth and the diagnosis was confirmed biochemically by demonstrating elevated 7-DHC in plasma. The family pursued prenatal diagnosis in their fourth, fifth, and sixth pregnancies. The fourth pregnancy spontaneously miscarried at 9 weeks' gestation. Analysis in both direct and cultured curetting tissue (identified as similar to CV tissue) showed an abnormal tissue neutral sterol pattern with an elevated 7-DHC concentration. The fifth pregnancy also miscarried spontaneously at 9 weeks but no tissue of unequivocal fetal origin could be identified to allow biochemical investigation. In the sixth pregnancy, ultrasound examination at the time of CV sampling showed a thickened nuchal fold. Direct analysis of the CV sample revealed elevated levels of 7-DHC consistent with the diagnosis of SLO. The pregnancy was terminated and both fetal tissue and cultured fetal cells showed marked increases in 7-DHC, confirming the prenatal diagnosis.