Prenatal Screening For Smith-Lemli-Opitz Syndrome

This study has been completed.
Information provided by:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Identifier:
First received: October 8, 2003
Last updated: June 28, 2007
Last verified: August 2005
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.

Condition Phase
Smith-Lemli-Opitz Syndrome
Phase 2

Study Type: Observational
Study Design: Observational Model: Defined Population
Primary Purpose: Screening
Time Perspective: Longitudinal
Official Title: The Feasibility of Screening for Smith-Lemli-Opitz Syndrome

Resource links provided by NLM:

Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Estimated Enrollment: 1800
Study Start Date: April 2001
Estimated Study Completion Date: July 2005
Detailed Description:

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.

Participants in this study will be pregnant women undergoing amnioscentisis during the second trimester. Women who have a positive test for SLOS will be asked to provide a urine and blood sample. The study will collect data on patient demographics and family history; data will also be obtained from the participant’s ultrasound, karyotype, alpha-fetoprotein, maternal serum screening, and SLOS reports. Three months after the pregnancy due date, a genetic counselor will contact the participant to obtain basic information about the baby’s delivery and health.


Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria

  • Pregnant, second trimester
  • Singleton pregnancy
  • Positive second trimester maternal serum screen for Smith-Lemli-Opitz Syndrome (using the Foundation for Blood Research screening algorithm )

Exclusion criteria:

  • Gestational age at time of serum collection outside the range accepted for Down Syndrome screening
  • Not pregnant
  • Twin/multiple pregnancy
  • Sample/clerical/assay error
  • Physician not participating in study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00070850

United States, Maine
Foundation for Blood Research
Scarborough, Maine, United States, 04074
Sponsors and Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Principal Investigator: James E. Haddow, M.D. Foundation for Blood Research
  More Information

Additional Information:
Publications: Identifier: NCT00070850     History of Changes
Other Study ID Numbers: R01HD038940 
Study First Received: October 8, 2003
Last Updated: June 28, 2007
Health Authority: United States: Federal Government

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Additional relevant MeSH terms:
Cleft Palate
Genetic Diseases, X-Linked
Smith-Lemli-Opitz Syndrome
Abnormalities, Multiple
Bone Diseases
Bone Diseases, Developmental
Congenital Abnormalities
Craniofacial Abnormalities
Craniofacial Dysostosis
Genetic Diseases, Inborn
Genital Diseases, Male
Jaw Abnormalities
Jaw Diseases
Lipid Metabolism Disorders
Lipid Metabolism, Inborn Errors
Maxillofacial Abnormalities
Metabolic Diseases
Metabolism, Inborn Errors
Mouth Abnormalities
Mouth Diseases
Musculoskeletal Abnormalities
Musculoskeletal Diseases
Pathologic Processes
Penile Diseases processed this record on May 26, 2016