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

Abstract

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.

• Authors: 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
• Journal: Prenatal diagnosis (Prenat Diagn) Vol. 26 Issue 9 Pg. 842-9 (Sep 2006) ISSN: 0197-3851 [Print] England
• PMID: 16832833 (Publication Type: Journal Article, Multicenter Study, Research Support, N.I.H., Extramural)

Chemical References

• Biomarkers
• Steroids

Topics

• Abnormalities, Multiple (diagnosis)
• Adult
• Algorithms
• Amniocentesis
• Biomarkers (blood, urine)
• Down Syndrome (diagnosis)
• Female
• Genetic Testing
• Humans
• Pregnancy
• Pregnancy Outcome
• Pregnancy Trimester, Second
• Prevalence
• Smith-Lemli-Opitz Syndrome (diagnosis, epidemiology)
• Steroids (blood, urine)
• United States (epidemiology)