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 external genitalia, a cardiac malformation and mid-trimester intra-uterine growth retardation by ultrasound examination. The maternal serum oestriol level was low. The combination of low oestriol and sonographic findings suggested Smith-Lemli-Opitz syndrome (SLO), which was confirmed by a markedly increased amniotic fluid level of 7-dehydrocholesterol. We review the differential 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 marker for SLO a follow-up study of 12141 pregnancies screened for Down syndrome using three biochemical markers: alpha-fetoprotein, beta-human chorionic gonadotrophin and oestriol was performed. 26 pregnancies had an oestriol level 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. Nine of the pregnancies ended in spontaneous miscarriage. Although the frequency of SLO in pregnancies with low maternal oestriol levels or sex-reversed fetuses is unknown, the diagnosis of SLO should, nevertheless, be considered in both clinical settings.