Smith-Lemli-Opitz syndrome: A multiple malformation/mental retardation syndrome caused by defective cholesterol synthesis

S. Ginat, Cheryl Maslen, W. E. Connor, F. D. Porter, R. D. Steiner

    Research output: Contribution to journalArticle

    Abstract

    Smith-Lemli-Opitz syndrome (SLOS) is a genetic condition characterized by dysmorphic facies, mental retardation and multiple malformations. A specific defect in cholesterol metabolism, 7-dehydrocholesterol-Δ7 reductase (DHCR7) deficiency due to mutation of the DHCR7 gene is the underlying cause of this syndrome. DHCR7 is a microsomal enzyme that catalyzes the conversion of 7-dehydrocholesterol (7DHC) to cholesterol. Hence, affected individuals exhibit low plasma cholesterol and high 7DHC levels. The phenotype most likely results from the combination of cholesterol deficiency and 7DHC accumulation. Diagnosis is based on clinical findings with confirmation by plasma sterol analysis. Prenatal diagnosis may be performed by sterol analysis of amniotic fluid/amniocytes or chorionic villi, or enzyme assay of chorionic villi. Maternal serum estriol and urine sterol analyses provide the opportunity for noninvasive prenatal diagnostic testing. Preliminary evidence from animal and human studies shows that dietary cholesterol supplementation may be beneficial for SLOS patients, but issues including prenatal onset of damage plus poor transport of cholesterol across the blood-brain barrier may limit treatment efficacy. The incidence of SLOS has been estimated to be one in 20,000 to one in 60,000 making it one of the most common autosomal recessive disorders. Recent studies suggest that the carrier frequency is much higher than the disease incidence would suggest.

    Original languageEnglish (US)
    Pages (from-to)300-313
    Number of pages14
    JournalEndocrinologist
    Volume10
    Issue number5
    StatePublished - 2000

    Fingerprint

    Smith-Lemli-Opitz Syndrome
    Intellectual Disability
    Cholesterol
    Sterols
    Chorionic Villi
    Dietary Cholesterol
    Estriol
    Incidence
    Enzyme Assays
    Amniotic Fluid
    Dietary Supplements
    Blood-Brain Barrier
    Prenatal Diagnosis
    Mothers
    Urine
    Phenotype
    Mutation
    Enzymes
    Serum
    Genes

    ASJC Scopus subject areas

    • Endocrinology

    Cite this

    Smith-Lemli-Opitz syndrome : A multiple malformation/mental retardation syndrome caused by defective cholesterol synthesis. / Ginat, S.; Maslen, Cheryl; Connor, W. E.; Porter, F. D.; Steiner, R. D.

    In: Endocrinologist, Vol. 10, No. 5, 2000, p. 300-313.

    Research output: Contribution to journalArticle

    Ginat, S. ; Maslen, Cheryl ; Connor, W. E. ; Porter, F. D. ; Steiner, R. D. / Smith-Lemli-Opitz syndrome : A multiple malformation/mental retardation syndrome caused by defective cholesterol synthesis. In: Endocrinologist. 2000 ; Vol. 10, No. 5. pp. 300-313.
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