RSH/Smith-Lemli-Opitz syndrome: a multiple congenital anomaly/mental retardation syndrome due to an inborn error of cholesterol biosynthesis.
The RSH/Smith-Lemli-Opitz syndrome (RSH/SLOS) is an autosomal recessive multiple congenital anomaly/mental retardation syndrome caused by an inborn error of cholesterol biosynthesis. The RSH/SLOS phenotypic spectrum is broad; however, typical features include microcephaly, ptosis, a small upturned nose, micrognathia, postaxial polydactaly, second and third toe syndactaly, genital anomalies, growth failure, and mental retardation. RSH/SLOS is due to a deficiency of the 3beta-hydroxysterol Delta(7)-reductase, which catalyzes the reduction of 7-dehydrocholesterol (7-DHC) to cholesterol. This inborn error of cholesterol biosynthesis results in elevated serum and tissue 7-DHC levels. The 3beta-hydroxysterol Delta(7)-reductase gene (DHCR7) maps to chromosome 11q12-13, and to date 66 different mutations of this gene have been identified in RSH/SLOS patients. Identification of the biochemical basis of RSH/SLOS has led to development of therapeutic regimens based on dietary cholesterol supplementation and has increased our understanding of the role cholesterol plays during embryonic development.
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Heritable Disorders Branch, National Institutes of Health, Bethesda, Maryland 20892-1830, USA.
D002648:Child; D002675:Child, Preschool; D002784:Cholesterol / Q000096:biosynthesis*; D005260:Female; D016142:Holoprosencephaly / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007223:Infant; D008297:Male; D008967:Molecular Biology; D009154:Mutation; D010088:Oxidoreductases / Q000172:deficiency / Q000235:genetics; D044925:Oxidoreductases Acting on CH-CH Group Donors; D010641:Phenotype; D019082:Smith-Lemli-Opitz Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
D002784:Cholesterol; D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors; C019995:7-dehydrocholesterol reductase