COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC:

Get the latest research information from NIH: Menu

Prenatal Screening For Smith-Lemli-Opitz Syndrome

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00070850
Recruitment Status : Completed
First Posted : October 13, 2003
Last Update Posted : July 2, 2007
Information provided by:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

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.

Condition or disease
Smith-Lemli-Opitz Syndrome Pregnancy

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.

Layout table for study information
Study Type : Observational
Enrollment : 1800 participants
Observational Model: Defined Population
Time Perspective: Prospective
Official Title: The Feasibility of Screening for Smith-Lemli-Opitz Syndrome
Study Start Date : April 2001
Study Completion Date : July 2005

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   Child, Adult, Older Adult
Sexes 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00070850

Layout table for location information
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)
Layout table for investigator information
Principal Investigator: James E. Haddow, M.D. Foundation for Blood Research
Additional Information:
Layout table for additonal information Identifier: NCT00070850    
Other Study ID Numbers: R01HD038940 ( U.S. NIH Grant/Contract )
First Posted: October 13, 2003    Key Record Dates
Last Update Posted: July 2, 2007
Last Verified: August 2005
Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):
Additional relevant MeSH terms:
Layout table for MeSH terms
Cleft Palate
Genetic Diseases, X-Linked
Smith-Lemli-Opitz Syndrome
Pathologic Processes
Jaw Abnormalities
Jaw Diseases
Musculoskeletal Diseases
Maxillofacial Abnormalities
Craniofacial Abnormalities
Musculoskeletal Abnormalities
Stomatognathic Diseases
Mouth Abnormalities
Mouth Diseases
Stomatognathic System Abnormalities
Congenital Abnormalities
Craniofacial Dysostosis
Bone Diseases, Developmental
Bone Diseases
Penile Diseases
Urogenital Abnormalities
Genetic Diseases, Inborn
Abnormalities, Multiple
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Steroid Metabolism, Inborn Errors