Smith-Lemli-Opitz syndrome.

Andrea De Barber, Yasemen Eroglu, Louise S. Merkens, Anuradha Pappu, Robert D. Steiner

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive, multiple congenital malformation and intellectual disability syndrome, with clinical characteristics that encompass a wide spectrum and great variability. Elucidation of the biochemical and genetic basis for SLOS, specifically understanding SLOS as a cholesterol deficiency syndrome caused by mutation in DHCR7, opened up enormous possibilities for therapeutic intervention. When cholesterol was discovered to be the activator of sonic hedgehog, cholesterol deficiency with inactivation of this developmental patterning gene was thought to be the cause of SLOS malformations, yet this explanation is overly simplistic. Despite these important research breakthroughs, there is no proven treatment for SLOS. Better animal models are needed to allow potential treatment testing and the study of disease pathophysiology, which is incompletely understood. Creation of human cellular models, especially models of brain cells, would be useful, and in vivo human studies are also essential. Biomarker development will be crucial in facilitating clinical trials in this rare condition, because the clinical phenotype can change over many years. Additional research in these and other areas is critical if we are to make headway towards ameliorating the effects of this devastating condition.

Original languageEnglish (US)
JournalExpert Reviews in Molecular Medicine
Volume13
DOIs
StatePublished - 2011

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Smith-Lemli-Opitz Syndrome
Cholesterol
Developmental Genes
Research
Intellectual Disability
Molecular Biology
Therapeutics
Animal Models
Biomarkers
Clinical Trials
Phenotype
Mutation
Brain

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine

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Smith-Lemli-Opitz syndrome. / De Barber, Andrea; Eroglu, Yasemen; Merkens, Louise S.; Pappu, Anuradha; Steiner, Robert D.

In: Expert Reviews in Molecular Medicine, Vol. 13, 2011.

Research output: Contribution to journalArticle

De Barber, Andrea ; Eroglu, Yasemen ; Merkens, Louise S. ; Pappu, Anuradha ; Steiner, Robert D. / Smith-Lemli-Opitz syndrome. In: Expert Reviews in Molecular Medicine. 2011 ; Vol. 13.
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