Prenatal diagnosis of Smith-Lemli-Opitz syndrome in a pregnancy with low maternal serum oestriol and a sex-reversed fetus

A cytogenetically normal male fetus was subsequently found to have female e xternal genitalia, a cardiac malformation and mid-trimester intra-uterine g rowth retardation by ultrasound examination. The maternal serum oestriol le vel was low. The combination of low oestriol and sonographic findings sugge sted Smith-Lemli-Opitz syndrome (SLO), which was confirmed by a markedly in creased amniotic fluid level of 7-dehydrocholesterol. We review the differe ntial diagnosis of apparent sex reversal in a fetus and low maternal serum oestriol level. To further examine the specificity of low maternal oestriol level as a mark er for SLO a follow-up study of 12 141 pregnancies screened for Down syndro me using three biochemical markers: alpha-fetoprotein, beta-human chorionic gonadotrophin and oestriol was performed. 26 pregnancies had an oestriol l evel that was 0.25 MoM or less. SLO was not diagnosed clinically in any of the liveborn children ascertained through a low maternal oestriol level. Ni ne of the pregnancies ended in spontaneous miscarriage. Although the freque ncy of SLO in pregnancies with low maternal oestriol levels or sex-reversed fetuses is unknown, the diagnosis of SLO should, nevertheless, be consider ed in both clinical settings. Copyright (C) 1999 John Wiley & Sons, Ltd.