Genetic basis of potential therapeutic strategies for craniosynostosis

Authors

  • Heather Melville,

    1. Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York
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  • Yingli Wang,

    1. Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York
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  • Peter J. Taub,

    1. Department of Surgery, Mount Sinai School of Medicine, New York, New York
    2. Department of Pediatrics, Mount Sinai School of Medicine, New York, New York
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  • Ethylin Wang Jabs

    Corresponding author
    1. Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York
    2. Department of Pediatrics, Mount Sinai School of Medicine, New York, New York
    3. Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, New York, New York
    • Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1497, New York, New York 10029.
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  • Heather Melville and Yingli Wang contributed equally to this work.

  • How to Cite this Article: Melville H, Wang Y, Taub PJ, Jabs EW. 2010. Genetic basis of potential therapeutic strategies for craniosynostosis. Am J Med Genet Part A 152A:3007–3015.

Abstract

Craniosynostosis, the premature fusion of one or more cranial sutures, is a common malformation of the skull that can result in facial deformity and increased intracranial pressure. Syndromic craniosynostosis is present in ∼15% of craniosynostosis patients and often is clinically diagnosed by neurocranial phenotype as well as various other skeletal abnormalities. The most common genetic mutations identified in syndromic craniosynostosis involve the fibroblast growth factor receptor (FGFR) family with other mutations occurring in genes for transcription factors TWIST, MSX2, and GLI3, and other proteins EFNB1, RAB23, RECQL4, and POR, presumed to be involved either upstream or downstream of the FGFR signaling pathway. Both syndromic and nonsyndromic craniosynostosis patients require early diagnosis and intervention. The premature suture fusion can impose pressure on the growing brain and cause continued abnormal postnatal craniofacial development. Currently, treatment options for craniosynostosis are almost exclusively surgical. Serious complications can occur in infants requiring either open or endoscopic repair and therefore the development of nonsurgical techniques is highly desirable although arguably difficult to design and implement. Genetic studies of aberrant signaling caused by mutations underlying craniosynostosis in in vitro calvarial culture and in vivo animal model systems have provided promising targets in designing genetic and pharmacologic strategies for systemic or adjuvant nonsurgical treatment. Here we will review the current literature and provide insights to future possibilities and limitations of therapeutic applications. © 2010 Wiley-Liss, Inc.

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