Identifying Smith–Lemli–Opitz syndrome in conjunction with prenatal screening for Down syndrome Academic Article uri icon

  • Overview
  • Research
  • Identity
  • Additional Document Info
  • View All


  • 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 130 000 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.


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

publication date

  • September 2006