The RSH/“Smith–Lemli–Opitz” Syndrome: Historical footnote


  • John M. Opitz,

    Corresponding author
    • American Journal of Medical Genetics, University of Utah, 419 Wakara Way, Ste 213, Salt Lake City, UT 84108.
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    • John M. Opitz is Professor of Medical Genetics in Pediatrics and adjunct Professor of Human Genetics, Pathology, Obstetrics and Gynecology at the University of Utah School of Medicine. Trained by Emil Witschi, Hans Zellweger, and Jacqueline A. Noonan in Iowa City, Klaus Patau and David Smith in Madison, he initially focused his work on the delineation and definition of syndromes, Mendelian and cytogenetic. With Elisabeth G. Kavaeggia in Madison and Philip D. Pallister in Boulder, MT, Dr. Opitz undertook major studies of mental retardation. With the move of Enid F. Gilbert (later Gilbert-Barness) to Madison Dr. Opitz became deeply involved in developmental pathology in humans, an interest continuing to this day, together with a study of the relationship between evolution and development (“everything that develops has evolved”).

  • Larissa V. Furtado

    Current affiliation:
    1. Department of Pathology, University of Michigan, 1301 Catherine St., 4242 Medical Science Bldg 1, Ann Arbor, MI 48109.
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    • Larissa V. Furtado is a Molecular Genetic Pathology Fellow at the University of Michigan Health System. She is involved in anatomic/clinical pathology and molecular genetics. Her research focus on the genetic aspects of perinatal and pediatric inherited disorders. A second research field includes the application of new genomic techniques to identify relevant genes associated with rare pediatric tumors.

  • How to cite this article: Opitz JM, Furtado LV. 2012. The RSH/“Smith–Lemli–Opitz” syndrome: Historical footnote. Am J Med Genet Part C Semin Med Genet 160C: 242–249.


Thirty years after its clinical delineation in humans and its teratologic simulation in rats, a Garrodian error of metabolism was discovered in the autosomal recessive RSH/SLO syndrome, namely defective conversion of 7-dehydrocholesterol to cholesterol due to the mutant 7-dehydrocholesterol reductase. This opened the door to the study of several other defects of sterol biosynthesis in humans and the creation of animal “models.” The gross discrepancy between expected and observed birth prevalence suggests high embryolethality. The discovery of the role of cholesterol in the synthesis of the morphogen sonic hedgehog has greatly advanced our understanding of mammalian development. © 2012 Wiley Periodicals, Inc.