Severe presentation of Beckwith–Wiedemann syndrome associated with high levels of constitutional paternal uniparental disomy for chromosome 11p15

Authors

  • Adam C. Smith,

    1. Institute of Medical Science, University of Toronto, Toronto, Canada
    2. Genetics and Genome Biology, Research Institute, Hospital for Sick Children, Toronto, Canada
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  • Cheryl Shuman,

    1. Genetics and Genome Biology, Research Institute, Hospital for Sick Children, Toronto, Canada
    2. Division of Clinical and Metabolic Genetics, Hospital for Sick Children, Toronto, Canada
    3. Department of Molecular Genetics, University of Toronto, Toronto, Canada
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  • David Chitayat,

    1. Division of Clinical and Metabolic Genetics, Hospital for Sick Children, Toronto, Canada
    2. Department of Molecular Genetics, University of Toronto, Toronto, Canada
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  • Leslie Steele,

    1. Department of Paediatric Laboratory Medicine, Hospital for Sick Children, Toronto, Canada
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  • Peter N. Ray,

    1. Genetics and Genome Biology, Research Institute, Hospital for Sick Children, Toronto, Canada
    2. Department of Molecular Genetics, University of Toronto, Toronto, Canada
    3. Department of Paediatric Laboratory Medicine, Hospital for Sick Children, Toronto, Canada
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  • Jaqueline Bourgeois,

    1. Department of Laboratory Medicine, McMaster University Medical Centre, Hamilton, Canada
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  • Rosanna Weksberg

    Corresponding author
    1. Institute of Medical Science, University of Toronto, Toronto, Canada
    2. Genetics and Genome Biology, Research Institute, Hospital for Sick Children, Toronto, Canada
    3. Division of Clinical and Metabolic Genetics, Hospital for Sick Children, Toronto, Canada
    4. Department of Molecular Genetics, University of Toronto, Toronto, Canada
    • Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, 555 University Ave., Toronto, ONT, Canada M5G 1X8.
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  • How to cite this article: Smith AC, Shuman C, Chitayat D, Steele L, Ray PN, Bourgeois J, Weksberg R. 2007. Severe presentation of Beckwith–Wiedemann syndrome associated with high levels of constitutional paternal uniparental disomy for chromosome 11p15. Am J Med Genet Part A 143A:3010–3015.

Abstract

Beckwith–Wiedemann syndrome (BWS) is an overgrowth syndrome characterized by macrosomia, macroglossia, omphalocele, hemihyperplasia, and increased tumor risk. BWS can be associated with genetic and/or epigenetic alterations that modify imprinted gene expression on chromosome 11p15.5. Somatic mosaicism for paternal uniparental disomy (UPD) of chromosome 11p15, found in 20% of BWS patients, is associated with specific features of BWS including hemihyperplasia, Wilms tumor, and hepatoblastoma. The highly variable phenotypic spectrum of BWS associated with UPD may well reflect the level of UPD 11 cells in specific organs and tissues such that very high levels of UPD might produce a more severe phenotypic expression of BWS. In this regard we report on two patients with severe presentations of BWS and extremely high levels of UPD in DNA from lymphocytes. Clinically, both patients demonstrated extreme macroglossia, persistent hypoglycemia, cardiomyopathy, hemihyperplasia, renal abnormalities, abdominal organomegaly, hepatoblastoma and died in the first 6 months of life. These two patients support the hypothesis that high levels of UPD define high expressivity in BWS. © 2007 Wiley-Liss, Inc.

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