Identifying Smith-Lemli-Opitz syndrome in conjunction with prenatal screening for Down syndrome

Wendy Y. Craig, James E. Haddow, Glenn E. Palomaki, Richard I. Kelley, Lisa E. Kratz, Cedric H.L. Shackleton, Josep Marcos, G. Stephen Tint, Andrew R. MacRae, Malgorzata J. Nowaczyk, Edward M. Kloza, Mira B. Irons, Marie Roberson

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


Background: Smith-Lemli-Opitz syndrome (SLOS) is a rare hereditary disorder of cholesterol metabolism. We examine the feasibility of identifying SLOS as a part of a routine prenatal screening and evaluate diagnostic testing in maternal urine (or serum), in addition to amniotic fluid. Methods: Our SLOS risk algorithm utilized three Down syndrome screening markers (estimated 62% detection rate; 0.3% screen-positive rate). Fifteen North American prenatal screening programs implemented this algorithm. Results: SLOS risk was assigned to 1 079 301 pregnancies; 3083 were screen-positive (0.29%). Explanations were found for 1174, including 914 existing fetal deaths. Among the remaining pregnancies, 739 were screen-positive only for SLOS; 1170 were also screen-positive for other fetal disorders. Five of six SLOS pregnancies (83%) were screen-positive. All six had sonographic findings, were biochemically confirmed, and were terminated. Maternal urine steroid measurements were confirmatory in four cases tested. Second-trimester prevalence among Caucasians was 1 in 101 000 (1 in 130000 overall; no cases in other racial groups). Among 739 pregnancies screen-positive only for SLOS. two cases were identified; another 69 had major fetal abnormalities. Conclusions: Although SLOS occurred less often than previously reported, many other major abnormalities were detected. Implementing the algorithm as an adjunct to Down syndrome screening may be feasible.

Original languageEnglish (US)
Pages (from-to)842-849
Number of pages8
JournalPrenatal Diagnosis
Issue number9
StatePublished - Sep 2006


  • Diagnostic testing
  • Prenatal screening
  • Prevalence
  • Smith-Lemli-Opitz syndrome

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Genetics(clinical)


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