View clinical trials related to Smith-Lemli-Opitz Syndrome.
Filter by:The purpose of this study is to determine whether dietary cholic acid therapy benefits people with Smith-Lemli-Opitz syndrome (SLOS) by leading to an increase in plasma cholesterol and reduction in harmful cholesterol precursors. SLOS participants will be treated with dietary cholic acid for 8 weeks and plasma cholesterol and cholesterol precursor metabolites will be measured.
The purpose of this study is to determine whether supplementation with an oil-based cholesterol suspension will correct the biochemical abnormalities in cholesterol and its precursors in individuals with the Smith-Lemli-Opitz syndrome.
This 10-week study will evaluate and compare behavior changes in children with Smith-Lemli-Opitz syndrome (SLOS) who are taking cholesterol supplementation versus those who are not on cholesterol supplementation. SLOS is a genetic disorder that affects the development of children both before and after birth. An enzyme deficiency in these children results in low levels of cholesterol, which can cause a variety of birth defects and behavioral problems. Typical abnormal physical features of patients include a small head, drooping eyelids, small upturned nose, small chin, cleft palate, heart defects, and extra fingers or toes. Children between 5 and 17 with mild SLOS who do not have a history of egg allergy or intolerance may be eligible for this study. Candidates are screened with a questionnaire about the patient's age, genotype (if known), sterol levels, symptoms, current treatment and medical history. Children participate in two 2-week study phases. Between the study phases the children will take 150 mg/kg daily of a cholesterol preparation typically used to supplement cholesterol in patients in SLOS studies at NIH. In the study phases, the participants are randomly assigned to take either egg yolk or an egg yolk substitute, such as Egg Beaters, that does not contain cholesterol. The study is done at the participant's home, and the cholesterol supplementation and egg/egg substitute are sent to the home each day with instructions on how to take them. The caretakers can stop the study phases after four days if behavior problems occur. The children's caretakers fill out a standard behavioral questionnaire, the Aberrant Behavior Checklist. The questionnaire is designed to assess the effects of treatment in mentally impaired persons.
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.
This study will evaluate the safety and effectiveness of simvastatin in treating children with Smith-Lemli-Opitz syndrome (SLOS). Patients with this inherited disease are deficient in an enzyme that converts a substance called 7-dehydrocholesterol (7-DHC) to cholesterol. Cholesterol synthesis is impaired, causing birth defects and mental retardation. This study will examine whether simvastatin can increase the amount of the deficient enzyme, thereby lowering 7-DHC and increasing cholesterol. It will examine the safety of simvastatin in affected children and its effects on their behavioral problems. Children between 4 and 18 years of age with mild to typical SLOS may be eligible for this study. Participants will be evaluated at the NIH Clinical Center in Bethesda, MD, and at the Kennedy Krieger Institute in Baltimore, MD, upon admission to the study and again at 6, 12, 20, and 26 months. The visits will last 3 to 4 days, and will include a medical history and physical examination, photographs to document medical findings, and other procedures detailed below. In addition, blood samples will be collected at 1, 3, 9, 14, 15, 17, and 23 months. Parents will complete several questionnaires during the study. Procedures include the following: - Simvastatin and cholesterol supplementation therapy. Patients take cholesterol supplements (50 milligrams per kilogram per day) plus simvastatin (0.5 mg/kg/day for 6 weeks and then 1 mg/kg/day) for 12 months, and cholesterol supplements plus a placebo for 12 months. - Blood draws to check liver, muscle, and kidney function, hormone levels, vitamin D levels, blood counts, cholesterol and 7-DHC levels, and lipoprotein levels. Some extra blood is drawn for research purposes. - Urine collection. Urine is collected using a toilet hat. For children who are not toilet trained, urine is collected in a bag taped to the skin with an adhesive. - Electroretinogram (ERG) to measure the function of the retina, the light-sensitive tissue at the back of the eye. ERG is done under sedation. After adapting the child's eyes to the dark, an electrode is taped to the child's forehead, the surface of one eye is numbed with eye drops, and a contact lens is placed on the eye. The child looks inside a globe that emits a series of light flashes. The contact lens senses electrical signals generated by the retina when the light flashes. After the ERG, the patient has a full eye exam, including pupil dilation and photographs of the eye. - Lumbar puncture (spinal tap) to collect a sample of cerebral spinal fluid (CSF). This procedure, done while the patient is sedated for the ERG, shows whether simvastatin affects brain cholesterol and chemical levels. Under local anesthetic, a needle is inserted in the space between the bones in the lower back where the CSF circulates below the spinal cord. A small amount of fluid is collected through the needle. - CRH stimulation test to detect hormone-related problems in cholesterol synthesis. The patient is given CRH, a hormone involved in cholesterol synthesis, through a plastic tube placed in a vein. Blood samples are collected through the same catheter to measure levels of other hormones involved in cholesterol production. - Electroencephalogram (EEG) to look at the electrical activity (brain waves) of the child's brain. - Activity monitoring. An activity monitor, which looks like and is worn like a watch, is used to record the child's level of activity for a 48-hour period. - Urine pregnancy test at every visit for female patients over age 10. - Skin swab for sterol (solid alcohol, such as cholesterol) analysis. An alcohol pad is rubbed lightly against the child's arm or thigh to collect skin cells. - Stool collection. A small stool sample is collected from the child's diaper or, for children who are toilet trained, from a toilet "hat" like that used to collect urine.
RSH/Smith-Lemli-Opitz syndrome (SLOS) is one that causes mental retardation. It is common in the Caucasian population but rare in African American and African black populations. It has been shown that SLOS is caused by a specific defect in DHCR7, an enzyme used in cholesterol metabolism. Studies have already been done to determine the frequency of the SLOS-causing mutations in various geographic Caucasian populations. This study will investigate the frequency of the DHCR7 mutations in the African American population. If the frequency observed suggests that SLOS cases are not being identified in this ethnic group, the study will provide the rationale for future studies to identify these patients. The sample size will be 1,600. The study population will consist of archived biological specimens in the form of newborn screening blood spots from two newborn screening centers, one in Maryland and one in Pennsylvania. Subjects will be of African American ethnicity, including blacks of African, Caribbean, and Central American descent. Genomic DNA will be extracted from blood spots and screened for the six common SLOS mutations. If SLOS syndrome is found, followup will be attempted for the Maryland samples (the Pennsylvania samples will be totally anonymous).
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. <TAB> What is the prognosis / natural history of the demyelination in the nervous system of patients with SLOS? 2. <TAB> Do patients with SLOS have other problems concerning the function of their endocrine systems? 3. <TAB>What are the genetic make-ups of patients with SLOS? 4. <TAB>Can further studies of cholesterol metabolism and genetic testing, using SLOS fibroblasts, increase the understanding of SLOS?<TAB>...