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.
Severe presentation of Beckwith–Wiedemann syndrome associated with high levels of constitutional paternal uniparental disomy for chromosome 11p15†
Article first published online: 13 NOV 2007
Copyright © 2007 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Special Issue: M. Michael Cohen Jr. Festschrift
Volume 143A, Issue 24, pages 3010–3015, 15 December 2007
How to Cite
Smith, A. C., Shuman, C., Chitayat, D., Steele, L., Ray, P. N., Bourgeois, J. and 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., 143A: 3010–3015. doi: 10.1002/ajmg.a.32030
- Issue published online: 28 NOV 2007
- Article first published online: 13 NOV 2007
- Manuscript Accepted: 5 AUG 2007
- Manuscript Received: 13 JUL 2007
- Canadian Institutes of Health Research
- growth regulatory genes;
- imprinted genes;
- imprinting control centers;
- Wilms tumor
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.