Clinical Trial: Prenatal Screening For Smith-Lemli-Opitz Syndrome

Study Status: Completed
Recruit Status: Completed
Study Type: Observational

Official Title: The Feasibility of Screening for Smith-Lemli-Opitz Syndrome

Brief Summary: Smith-Lemli-Opitz Syndrome (SLOS) is a genetic condition that causes mental retardation and other birth defects. This study will evaluate a new prenatal screening test for SLOS.

Detailed Summary:

SLOS is an inherited metabolic disorder characterized by moderate to severe mental retardation and congenital anomalies. SLOS is caused by a deficiency of the enzyme 7-dehydrocholesterol reductase and the resulting defect in the conversion of 7-dehydrocholesterol to cholesterol. SLOS can now be reliably detected prenatally by analysis of amniotic fluid 7-8- dehydrocholesterol (7/8-DHC) levels. Unconjugated estriol (uE3) is one of the maternal serum analytes currently measured routinely to screen for Down syndrome. This analyte requires cholesterol as a precursor, and its concentration in maternal serum is lower when the fetus has SLOS.

Currently, there is no national standard for the approach taken in prenatal screening; existing programs vary both in availability and in the protocol and algorithms used. The major barrier to identifying SLOS prenatally is the absence of sound screening methodology that takes into account the detection rate, the false positive rate, and the prevalence. This study will evaluate the efficacy of routinely identifying Smith-Lemli-Opitz Syndrome (SLOS) prenatally.

The screening model in this study is based on data from SLOS pregnancies and will be tested in 1,000,000 pregnancies in which maternal serum uE3, alpha-fetoprotein, and human chorionic gonadotrophin measurements are being done as part of routine screening for Down syndrome. The screening false positive rate is projected to be 0.34%, the detection rate 62%, and the odds of being affected given a positive screening result 1:70. These rates all compare favorably with prenatal screening tests now in routine use. The study will also determine whether SLOS diagnostic studies can be carried out in maternal urine or serum, rather than amniotic fluid, thereby avoiding invasive procedures.

Partic
Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

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Information By: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Dates:
Date Received: October 8, 2003
Date Started: April 2001
Date Completion: July 2005
Last Updated: June 28, 2007
Last Verified: August 2005