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Smith–Lemli–Opitz syndrome

Published online by Cambridge University Press:  22 July 2011

Andrea E. DeBarber ,
Yasemen Eroglu ,
Louise S. Merkens ,
Anuradha S. Pappu  and
Robert D. Steiner
Andrea E. DeBarber
Affiliation:
Department of Physiology and Pharmacology, Oregon Health & Science University (OHSU), Portland, OR, USA
Yasemen Eroglu
Affiliation:
Pediatric Gastroenterology, Oregon Health & Science University (OHSU), Portland, OR, USA Department of Pediatrics, Oregon Health & Science University (OHSU), Portland, OR, USA
Louise S. Merkens
Affiliation:
Department of Pediatrics, Oregon Health & Science University (OHSU), Portland, OR, USA
Anuradha S. Pappu
Affiliation:
Department of Physiology and Pharmacology, Oregon Health & Science University (OHSU), Portland, OR, USA Department of Pediatrics, Oregon Health & Science University (OHSU), Portland, OR, USA
Robert D. Steiner*
Affiliation:
Department of Pediatrics, Oregon Health & Science University (OHSU), Portland, OR, USA Department of Molecular & Medical Genetics, Child Development and Rehabilitation Center, Doernbecher Children's Hospital, OHSU, Portland, OR, USA
*
*Corresponding author: Robert D. Steiner, Department of Pediatrics, OHSU, Portland, OR 97239, USA. E-mail: [email protected]
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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.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 13 , March 2011 , e24
Copyright
Copyright © Cambridge University Press 2011

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References

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Further reading, resources and contacts

There are several websites of interest for families of patients and researchers of SLOS.

The Smith-Lemli-Opitz/RSH Foundation website:

http://www.smithlemliopitz.org/.Google Scholar
http://www.ncbi.nlm.nih.gov/books/NBK1143/.Google Scholar
http://emedicine.medscape.com/article/949125-overview.Google Scholar
http://rarediseasesnetwork.epi.usf.edu/STAIR/index.htm.Google Scholar