Smith-Lemli-Opitz Syndrome
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What is Smith-Lemli-Opitz syndrome?Smith-Lemli-Opitz syndrome is a developmental disorder that affects many parts of the body. This condition is characterized by distinctive facial features, small head size (microcephaly), mental retardation or learning disabilities, and behavioral problems. Malformations of the heart, lungs, kidneys, gastrointestinal tract, and genitalia are also common. Infants with Smith-Lemli-Opitz syndrome have weak muscle tone (hypotonia), experience feeding difficulties, and tend to grow more slowly than other infants. Most affected individuals have fused second and third toes (syndactyly), and some have extra fingers or toes (polydactyly). The signs and symptoms of Smith-Lemli-Opitz syndrome vary widely. Mildly affected individuals may have only minor physical abnormalities with learning and behavioral problems. Severe cases can be life-threatening and involve profound mental retardation and major physical abnormalities. How common is Smith-Lemli-Opitz syndrome?Smith-Lemli-Opitz syndrome affects an estimated 1 in 20,000 to 40,000 births. This condition is most common in Caucasians (whites) of European ancestry. It is very rare among African and Asian populations. What genes are related to Smith-Lemli-Opitz syndrome?Mutations in the DHCR7 gene cause Smith-Lemli-Opitz syndrome. The DHCR7 gene makes an enzyme called 7-dehydrocholesterol reductase. This enzyme is responsible for the final step in the production of cholesterol. Cholesterol is a fat-like substance that is found in some foods and is also produced by the body. It is an essential nutrient that is necessary for normal embryonic development. Cholesterol is also a structural component of cell membranes and the protective substance covering nerve cells (myelin). Additionally, cholesterol plays an important role in the production of certain hormones and digestive acids. Mutations in the DHCR7 gene reduce or eliminate the activity of 7-dehydrocholesterol reductase, preventing cells from producing enough cholesterol. A lack of this enzyme also allows potentially toxic byproducts of cholesterol production to build up in the blood and other tissues. The combination of low cholesterol levels and an accumulation of other substances likely disrupts the growth and development of many body systems. It is not known, however, how this disturbance in cholesterol production leads to the specific features of Smith-Lemli-Opitz syndrome. How do people inherit Smith-Lemli-Opitz syndrome?This condition is inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder each carry one copy of the altered gene but do not show signs and symptoms of the disorder.
Source: National Institutes of Health
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Researchers from Medical College of Wisconsin report details of new studies and findings in the area of smith-lemli-opitz syndrome genetics
2007 MAY 29 -- Research findings, "Loss of apolipoprotein E exacerbates the neonatal lethality of the Smith-Lemli-Opitz syndrome mouse," are discussed in a new report. According to recent research from the United States, "The Smith-Lemli-Opitz syndrome (SLOS) is caused by a genetic defect in cholesterol biosynthesis; mutations in the enzyme 3ss-hydroxysterol Delta7 reductase (Dhcr7) lead to a failure of cholesterol (and desmosterol) synthesis, with an accumulation of precursor sterols, such as 7-dehydrocholesterol. Extensive genotype-phenotype analyses have indicated that there is considerable variation in the severity of the disease, much of which is not explained by defects in the Dhcr7 gene alone." "Factors ranging from variations in maternal-fetal cholesterol transfer during pregnancy, to other genetic factors have been proposed to account for this variability. Variations at the APOE locus affect plasma cholesterol levels in humans and this polymorphic gene has been found to be associated with cardiovascular as well as neurological disorders. This locus has recently been implicated in accounting for some of the variations in SLOS. To address whether maternal hypercholesterolemia can affect fetal outcome, we tested the ability of maternal hypercholesterolemia to rescue the neonatal lethality in a mouse model of SLOS. Maternal hypercholesterolemia, induced by ApoE or Ldl-r deficiency not only failed to ameliorate the postnatal lethality, it increased the prenatal mortality of Dhcr7 deficient pups," wrote C. Solcą and colleagues, Medical College of Wisconsin. The researchers concluded: "Thus the murine data suggest that maternal loss of ApoE or Ldl-r function further exacerbates the neonatal lethality, suggesting they may play a role in maternal transfer of cholesterol to the embryo." Solcą and colleagues published their study in Molecular Genetics and Metabolism (Loss of apolipoprotein E exacerbates the neonatal lethality of the Smith-Lemli-Opitz syndrome mouse. Molecular Genetics and Metabolism, 2007;91(1):7-14). For additional information, contact C. Solcą, Metabolism and Clinical Nutrition, Division of Endocrinology, Medical College of Wisconsin, Milwaukee, WI 53226 USA. Publisher contact information for the journal Molecular Genetics and Metabolism is: Academic Press Inc. Elsevier Science, 525 B St., Ste. 1900, San Diego, CA 92101-4495, USA. Keywords: United States, Milwaukee, Smith-Lemli-Opitz Syndrome Genetics, Genetics, Metabolism, Smith-Lemli-Opitz Syndrome. This article was prepared by Life Science Weekly editors from staff and other reports. Copyright 2007, Life Science Weekly via NewsRx.com.
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