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.


CONCLUSIONS
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.
Counsyl, South San Francisco, CA, USA.
Gabriel A
http://orcid.org/0000-0001-5061-8595
GA
Lazarin
Counsyl, South San Francisco, CA, USA.
Imran S
IS
Haque
Counsyl, South San Francisco, CA, USA.
Eric A
EA
Evans
Counsyl, South San Francisco, CA, USA.
James D
JD
Goldberg
D005260:Female; D046689:Fetal Mortality; D005787:Gene Frequency; D006580:Genetic Carrier Screening / Q000379:methods; D005820:Genetic Testing; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods / Q000706:statistics & numerical data; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA; D019082:Smith-Lemli-Opitz Syndrome / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality*