title: The placenta in Beckwith-Wiedemann syndrome:  genotype-phenotype associations, excessive extravillous trophoblast and placental mesenchymal dysplasia.
abstract: OBJECTIVE
  Placental mesenchymal dysplasia (PMD) is a rare condition which is associated with the disparate fetal outcomes of Beckwith-Wiedemann syndrome (BWS), fetal growth restriction or intrauterine and neonatal death. We aimed to investigate the potential epigenetic/genetic anomalies associated with PMD and their relationship with the different causes of BWS.
  
  
  METHODS
  Eight archival cases in which PMD, BWS or both were diagnosed were investigated by correlating morphology with p57 Kip2 expression, XY fluorescence in situ hybridisation (FISH) analysis and DNA genotyping.
  
  
  RESULTS
  Placentae from BWS cases caused by aberrant IC2 methylation, leading to abnormal p57 Kip2 expression, did not show PMD but had a striking excess of extravillous trophoblast. PMD in the absence of BWS was caused by androgenetic/biparental mosaicism. The single case of BWS with PMD was due to mosaic uniparental disomy of 11p15.5. In the latter two aetiologies, our results indicate that the uniparental disomy is confined to the villous mesenchyme.
  
  
  CONCLUSIONS
  These results suggest that the link between PMD and BWS is uniparental disomy of genes confined to the telomeric IC1 region of 11p15.5. A strong candidate gene is IGF2, a known growth factor of placental mesenchyme.
authors: Anatomical Pathology, Mater Health Services, Raymond Terrace, South Brisbane, Qld 4101, Australia. jane.armes@mater.org.au
authors: Jane E
authors: JE
authors: Armes
authors: Ivan
authors: I
authors: McGown
authors: Mark
authors: M
authors: Williams
authors: Amy
authors: A
authors: Broomfield
authors: Karen
authors: K
authors: Gough
authors: Fiona
authors: F
authors: Lehane
authors: Rohan
authors: R
authors: Lourie
mesh_terms: D001506:Beckwith-Wiedemann Syndrome / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002880:Chromosomes, Human, Pair 11; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D057890:Epigenomics; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D010920:Placenta / Q000378:metabolism / Q000473:pathology*; D011247:Pregnancy; D014327:Trophoblasts / Q000378:metabolism / Q000473:pathology*
chemical_list: D050761:Cyclin-Dependent Kinase Inhibitor p57; C035170:IGF2 protein, human; D007335:Insulin-Like Growth Factor II