Clinical Trial: Study of Smith-Lemli-Opitz Syndrome

This study is currently recruiting patients.

Sponsored by: National Institute of Child Health and Human Development (NICHD)
Information provided by: Warren G Magnuson Clinical Center (CC)


Smith-Lemli-Opitz Syndrome (SLOS) is a genetic disorder (autosomal recessive) caused by an abnormality in the production of cholesterol. The disorder can occur in both a "mild" or "severe" form. SLOS is associated with multiple birth defects and mental retardation. Some of the birth defects include; abnormal facial features, poor muscle tone, poor growth, shortened life span, and abnormalities of the heart, lungs, brain, gastrointestinal tract, limbs, genitalia, and kidneys.

There is no known cure for SLOS but recently patients have been treated with increased amounts of cholesterol in their diet. The cholesterol in a persons diet is unable to correct the abnormalities in the patient's organs, but researchers hope it will improve growth failure and mental retardation.

This study was developed to answer questions about the causes and complications of SLOS, as well as the effectiveness of cholesterol treatment. The study will enroll patients diagnosed with SLOS, and their mothers. The objectives of the study will be to address the following questions:

1. What is the prognosis / natural history of the demyelination in the nervous system of patients with SLOS?

2. Do patients with SLOS have other problems concerning the function of their endocrine systems?

3. What are the genetic make-ups of patients with SLOS?

4. Can further studies of cholesterol metabolism and genetic testing, using SLOS fibroblasts, increase the understanding of SLOS?

Condition Treatment or Intervention
Inborn Errors of Metabolism
Mental Retardation
Muscle Hypotonia
Smith Lemli Opitz Syndrome
 Drug: Cholesterol Suspension

MedlinePlus related topics:  Birth Defects;   Developmental Disabilities;   Genetic Disorders;   Metabolic Disorders;   Neurologic Diseases

Study Type: Observational
Study Design: Natural History

Official Title: Clinical and Basic Investigations into Smith-Lemli-Opitz Syndrome

Further Study Details: 

Expected Total Enrollment:  105

Study start: March 19, 1998

The Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive multiple congenital anomaly/mental retardation syndrome. Typical clinical features include a distinctive facial appearance, mental retardation, autistic behavior, hypotonia, failure to feed, poor growth, decreased life span, and variable structural anomalies of the heart, lungs, brain, gastrointestinal tract, limbs, genitalia and kidneys. The SLOS phenotypic spectrum is broad and variable. At the severe end of the spectrum SLOS is a lethal disorder with multiple major congenital anomalies; whereas, mild cases of SLOS present with a combination of minor physical stigmata, behavioral problems, and learning disabilities. SLOS is due to an inborn error of cholesterol biosynthesis. Biochemically, SLOS patients have a deficiency of 3beta-hydroxysterol delta(7)-reductase activity. 3beta-hydroxysterol delta(7)-reductase is an NADPH dependent microsomal enzyme that catalyzes the reduction of the C7(8) double bond of 7-dehydrocholesterol (7-DHC) to yield cholesterol in the last step of cholesterol biosynthesis via the Kandutsch-Russel pathway. This inborn error of cholesterol biosynthesis results in elevated tissue and serum 7DHC levels and typically decreased serum and tissue cholesterol levels. In 1998 we established that the deficiency in 3beta-hydroxysterol delta(7)-reductase activity is due to mutation of the 3beta-hydroxysterol delta(7)-reductase gene (DHCR7). Once the biochemical defect in SLOS was identified, dietary cholesterol supplementation was proposed and employed as a therapeutic approach. Although development malformations remain fixed, dietary cholesterol supplementation has improved the overall health of these patients, and initial results have shown that dietary cholesterol supplementation has had a positive impact on some of the behavioral manifestations of this disorder. Although our understanding of this disorder has advanced over the last few years, many questions remain concerning the effectiveness of cholesterol replacement therapy, the long term prognosis for individuals on dietary cholesterol supplementation, and the need for adjunctive measures in the clinical management of SLOS patients. We propose to answer some of these questions by continuing our longitudinal natural history/prognosis study on forty patients with SLOS.

The objectives of this study are as follows:

1. To establish the natural history, and thus prognoses, of a cohort of SLOS patients on dietary cholesterol supplementation.

2. To provide baseline information about SLOS patients on cholesterol supplementation in order to design and interpret future adjunctive therapies.

3. To develop clinical tools to determine the prognosis/natural history of central nervous system changes in SLOS.

4. To determine the extent to which endocrinological abnormalities in SLOS need to be considered in the clinical management of SLOS patients, and how they affect the clinical prognosis.

5. To establish a genotype/phenotype correlation for SLOS, and to determine other factors which may significantly influence a specific patient's phenotype.

6. To use in vitro studies of cholesterol metabolism in SLOS fibroblasts to further our understanding of the molecular, biochemical, and cellular processes which underlie the clinical problems encountered in SLOS


Genders Eligible for Study:  Both


Patient Selection
Patients will be diagnosed as having SLOS based on an elevated 7DHC level. For patients who this test has not previously been obtained, we will help primary care physician in obtaining these results before admitting the patient to this study. No exclusions are based on age, sex, or ethnicity. Patients will be excluded if they cannot travel to NIH because of their medical condition, or are pregnant.
Biological parents of enrolled patients with SLOS will be enrolled as obligate hereozygote patients. Since genetic testing is available to establish carrier status, biological fathers are also eligible for this aspect of the study.
Any patient with biochemically confirmed SLOS will be accepted into this study.
Patients of any age, either gender, or any ethnicity will be accepted into this study.
No exclusions will be made based on race or gender.
1. Patients will be excluded if they cannot travel to the NIH because of their medical condition.
2. Pregnant women will be excluded, and a negative urine pregnancy test will be required of menstruating women.
3. Patients with a history of coagulopathy will be excluded from the periodontal evaluation.
4. Patients at risk for bacterial endocarditis who cannot be adequately protected with prophylactic antibiotics will be excluded from the periodontal examination.

Location and Contact Information

      National Institute of Child Health and Human Development (NICHD), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting
Patient Recruitment and Public Liaison Office  1-800-411-1222 
TTY  1-866-411-1010 

More Information

Detailed Web Page


Elias ER, Irons MB, Hurley AD, Tint GS, Salen G. Clinical effects of cholesterol supplementation in six patients with the Smith-Lemli-Opitz syndrome (SLOS) Am J Med Genet. 1997 Jan 31;68(3):305-10.

Irons M, Elias ER, Abuelo D, Bull MJ, Greene CL, Johnson VP, Keppen L, Schanen C, Tint GS, Salen G. Treatment of Smith-Lemli-Opitz syndrome: results of a multicenter trial. Am J Med Genet. 1997 Jan 31;68(3):311-4.

Opitz JM. RSH/SLO ("Smith-Lemli-Opitz") syndrome: historical, genetic, and developmental considerations. Am J Med Genet. 1994 May 1;50(4):344-6. Review.

Study ID Numbers:  980081; 98-CH-0081
Record last reviewed:  March 9, 2005
Last Updated:  March 18, 2005
Record first received:  November 3, 1999 Identifier:  NCT00001721
Health Authority: United States: Federal Government processed this record on 2005-04-08

Cache Date: April 9, 2005