title: Severe presentation of Beckwith-Wiedemann syndrome associated with high levels of constitutional paternal uniparental disomy for chromosome 11p15.
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.
authors.affiliation: Institute of Medical Science, University of Toronto, Toronto, Canada.
authors.forename: Adam C
authors.initials: AC
authors.lastname: Smith
authors.forename: Cheryl
authors.initials: C
authors.lastname: Shuman
authors.forename: David
authors.initials: D
authors.lastname: Chitayat
authors.forename: Leslie
authors.initials: L
authors.lastname: Steele
authors.forename: Peter N
authors.initials: PN
authors.lastname: Ray
authors.forename: Jaqueline
authors.initials: J
authors.lastname: Bourgeois
authors.forename: Rosanna
authors.initials: R
authors.lastname: Weksberg
mesh_terms: D000782:Aneuploidy; D001506:Beckwith-Wiedemann Syndrome / Q000175:diagnosis* / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11; D044127:Epigenesis, Genetic; D017809:Fatal Outcome; D005260:Female; D005786:Gene Expression Regulation; D018392:Genomic Imprinting; D006801:Humans; D007223:Infant; D008297:Male; D010641:Phenotype; D012306:Risk; D017422:Sequence Analysis, DNA; D024182:Uniparental Disomy