Smith-Lemli-Opitz syndrome carrier frequency and estimates of in utero mortality rates.

Objective: To tabulate individual allele frequencies and total carrier frequency for Smith-Lemli-Opitz syndrome (SLOS) and compare expected versus observed birth incidences.

Methods: A total of 262 399 individuals with no known indication or increased probability of SLOS carrier status, primarily US based, were screened for SLOS mutations as part of an expanded carrier screening panel. Results were retrospectively analyzed to estimate carrier frequencies in multiple ethnic groups. SLOS birth incidences obtained from existing literature were then compared with these data to estimate the effect of SLOS on fetal survival.

Results: Smith-Lemli-Opitz syndrome carrier frequency is highest in Ashkenazi Jews (1 in 43) and Northern Europeans (1 in 54). Comparing predicted birth incidence with that observed in published literature suggests that approximately 42% to 88% of affected conceptuses experience prenatal demise.

Conclusion: Smith-Lemli-Opitz syndrome is relatively frequent in certain populations and, because of its impact on prenatal and postnatal morbidity and mortality, merits consideration for routine screening. © 2017 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd.