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Sponsored by: |
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) |
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Information provided by: | National Institutes of Health Clinical Center (CC) |
ClinicalTrials.gov Identifier: | NCT00001721 |
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:
Condition |
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Abnormalities Inborn Errors of Metabolism Mental Retardation Muscle Hypotonia Smith Lemli Opitz Syndrome |
Study Type: | Observational |
Official Title: | Clinical and Basic Investigations Into Smith-Lemli-Opitz Syndrome |
Estimated Enrollment: | 130 |
Study Start Date: | March 1998 |
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-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 7-DHC 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 developmental malformations remain fixed, dietary cholesterol supplementation appears to improve 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 patients with SLOS.
The objectives of this study are as follows:
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Patients will be diagnosed as having SLOS based on an elevated 7-DHC 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 heterozygote patients. Since genetic testing is available to establish carrier status, biological fathers are also eligible for this aspect of the study.
Contact: Patient Recruitment and Public Liaison Office | (800) 411-1222 | prpl@mail.cc.nih.gov |
Contact: TTY | 1-866-411-1010 |
United States, Maryland | |
National Institutes of Health Clinical Center, 9000 Rockville Pike | Recruiting |
Bethesda, Maryland, United States, 20892 |
Study ID Numbers: | 980081, 98-CH-0081 |
Study First Received: | November 3, 1999 |
Last Updated: | July 18, 2008 |
ClinicalTrials.gov Identifier: | NCT00001721 |
Health Authority: | United States: Federal Government |
Dysmorphology Cholesterol Endocrine |
MRI Demyelination Smith-Lemli-Opitz Syndrome (SLO) |
Lipid Metabolism, Inborn Errors Opitz syndrome Metabolic Diseases Smith-Lemli-Opitz Syndrome Mental Retardation Metabolism, Inborn Errors Signs and Symptoms Genetic Diseases, Inborn Mental Disorders |
Muscle Hypotonia Mental Disorders Diagnosed in Childhood Abnormalities, Multiple Neurologic Manifestations Metabolic disorder Congenital Abnormalities Neurobehavioral Manifestations Dyslipidemias Lipid Metabolism Disorders |
Neuromuscular Manifestations Pathologic Processes Disease |
Syndrome Nervous System Diseases Steroid Metabolism, Inborn Errors |