Abnormal sterol metabolism in holoprosencephaly


  • Dorothea Haas,

    Corresponding author
    • Division of Inborn Metabolic Diseases, Department of General Pediatrics, University Children's Hospital, Im Neuenheimer Feld 430, D-69120 Heidelberg, Germany.
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    • Dorothea Haas is a senior pediatrician and metabolic consultant at the University Children's Hospital of Heidelberg. Her clinical and research interests have focused on inborn errors of cholesterol biosynthesis.

  • Maximilian Muenke

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    • Maximilian Muenke is the chief of the Medical Genetics Branch at the National Human Genome Research Institute, NIH. His research interests include the genetics of holoprosencephaly and attention deficit hyperactivity disorders.

  • How to cite this article: Haas D, Muenke M. 2010. Abnormal sterol metabolism in holoprosencephaly. Am J Med Genet Part C Semin Med Genet 154C:102–108.


Holoprosencephaly (HPE) is the most common structural malformation of the developing forebrain in humans. The HPE phenotype is extremely variable and the etiology is heterogeneous. Among a variety of embryological toxins that can induce HPE, inhibitors, and other pertubations of cholesterol biosynthesis have been shown to be important factors, most likely because cholesterol is required in the Sonic hedgehog signaling cascade. Decreased levels of maternal cholesterol during pregnancy increase the risk for preterm delivery, but they are not associated with congenital malformations. However, if the fetus is affected by an inborn error of endogenous cholesterol synthesis, a reduction of maternal cholesterol concentration and cholesterol transport over the placenta aggravates the phenotypic expression. Exposure to lipophilic statins in early pregnancy may be associated with a substantial risk for structural CNS defects. © 2010 Wiley-Liss, Inc.