Smith-Lemli-Opitz syndrome (SLOS) is caused by an inborn error of cholesterol metabolism that results in deficiency of cholesterol and accumulation of the cholesterol precursor, 7-dehydrocholesterol (DHC) and its isomer, 8-DHC. Affected patients present with dysmorphic facial features, congenital anomalies, and growth and mental retardation. Postnatal treatment with cholesterol supplementation has been shown to improve plasma sterol levels in most patients. The most significant clinical improvement is seen in patients who began treatment at the youngest ages.

We report the first case of prenatal therapy of SLOS in a fetus initially identified by sonography with intrauterine growth restriction and ambiguous genitalia. The diagnosis of SLOS was confirmed by sterol analysis of amniotic fluid which revealed an elevation of 7- and 8-DHC. Antenatal supplementation of cholesterol was provided by intravenous and intraperitoneal transfusions of fresh frozen plasma. Three transfusions were administered at weekly intervals at 34-6/7, 35-6/7, and 37 weeks gestation. Fetal plasma cholesterol levels rose from 13.9 to 28 mg/dl, fetal red cell mean corpuscular volume (MCV) rose from 93.5 to 101 (fl), and maternal estriol levels rose, if at all, modestly(1.74 to 2.54 ng/ml) prior to delivery. The rise in fetal MCV suggests that the exogenous cholesterol was absorbed and was utilized. Both mother and fetus tolerated the procedures well and the infant was delivered at 37-4/7 weeks with Apgar scores of 7 and 9.

In summary, antenatal treatment of SLOS by cholesterol supplementation is feasible, but longer follow-up and a larger treatment group are necessary before conclusions about efficacy can be made. SLOS has been added to the growing list of human genetic disorders for which prenatal diagnosis is available and prenatal intervention is possible.