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Beckwith–Wiedemann syndrome

Authors

  • Sanaa Choufani,

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    • Sanaa Choufani, Ph.D., is a Research Associate at the Department of Genetics and Genome Biology at the Hospital for Sick Children. She has published research articles in the areas of cardiovascular research, autism and growth-related disorders, epigenetics and genomic imprinting.

  • Cheryl Shuman,

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    • Cheryl Shuman, M.S., C.G.C. is the Director, Genetic Counseling, Hospital for Sick Children and Program Director, MSc Program in Genetic Counseling, University of Toronto. She has a long-standing involvement in research and in clinical care for children and families with imprinting disorders, most notably Beckwith–Wiedemann syndrome and isolated hemihyperplasia.

  • Rosanna Weksberg

    Corresponding author
    • Clinical and Metabolic Genetics, The Hospital for Sick Children, 555 University Ave., Toronto, Ontario, Canada M5G 1X8.
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    • Rosanna Weksberg, M.D., Ph.D., is a Professor of Pediatrics and Molecular Genetics at the Hospital for Sick Children and the University of Toronto. She has published research articles in the areas of neurobehavioural and growth-related disorders, epigenetics and genomic imprinting, as well as the effects of environmental exposures, such as assisted reproduction, on epigenetic regulation.


  • How to cite this article: Choufani S, Shuman C, Weksberg R. 2010. Beckwith–Wiedemann syndrome. Am J Med Genet Part C 153C:343–354.

Abstract

Beckwith–Wiedemann syndrome (BWS) is an imprinting disorder characterized by overgrowth, tumor predisposition, and congenital malformations. Approximately 85% of reported BWS cases are sporadic, while the remaining 15% are familial. BWS is caused by epigenetic or genomic alterations which disrupt genes in one or both of the two imprinted domains on chromosome 11p15.5. In each domain, an imprinting center regulates the expression of imprinted genes in cis. Normally in domain 1, insulin-like growth factor 2 (IGF2) and the untranslated mRNA H19 are monoallelically expressed. In BWS, increased expression of IGF2 occurs via several mechanisms. In domain 2, CDKN1C, a growth repressor, and an untranslated RNA, KCNQ1OT1, are normally expressed monoallelically. In cases of BWS, several mechanisms result in reduced expression of CDKN1C. Recent reports of BWS cases have identified mutations outside the chromosome 11p15.5 critical region, thereby broadening the challenges in the diagnosis and genetic counseling of individuals and families with BWS. © 2010 Wiley-Liss, Inc.

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