title: Beckwith-Wiedemann and Russell-Silver Syndromes: from new molecular insights to the comprehension of imprinting regulation.
abstract: OBJECTIVE
  The imprinted human 11p15.5 region encompasses two imprinted domains important for the control of fetal growth: the H19/IGF2 domain in the telomeric region and the KCNQ1OT1/CDKN1C domain in the centromeric region. These two domains are differentially methylated and each is regulated by its own imprinting control region (ICR): ICR1 in the telomeric region and ICR2 in the centromeric region. Aberrant methylation of the 11p15.5 imprinted region, through genetic or epigenetic mechanisms, leads to two clinical syndromes, with opposite growth phenotypes: Russell-Silver Syndrome (RSS; with severe fetal and postnatal growth retardation) and Beckwith-Wiedemann Syndrome (BWS; an overgrowth syndrome).
  
  
  RESULTS
  In this review, we discuss the recently identified molecular abnormalities at 11p15.5 involved in RSS and BWS, which have led to the identification of cis-acting elements and trans-acting regulatory factors involved in the regulation of imprinting in this region. We also discuss the multilocus imprinting disorders identified in various human syndromes, their clinical outcomes and their impact on commonly identified metabolism disorders.
  
  
  CONCLUSIONS
  These new findings and progress in this field will have direct consequence for diagnostic and predictive tools, risk assessment and genetic counseling for these syndromes.
authors: aAP-HP, Hôpital Armand Trousseau, Explorations Fonctionnelles Endocriniennes bUPMC Paris 6, UMR_S938, Centre de Recherche de Saint-Antoine cINSERM, UMR_S938, Centre de Recherche de Saint-Antoine, Paris, France.
authors: Salah
authors: S
authors: Azzi
authors: Walid
authors: W
authors: Abi Habib
authors: Irene
authors: I
authors: Netchine
mesh_terms: D001506:Beckwith-Wiedemann Syndrome / Q000175:diagnosis / Q000235:genetics*; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D005817:Genetic Counseling; D005820:Genetic Testing / Q000379:methods* / Q000639:trends; D018392:Genomic Imprinting; D006801:Humans; D007231:Infant, Newborn; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D008297:Male; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics; D017410:Practice Guidelines as Topic; D011247:Pregnancy; D018570:Risk Assessment; D056730:Silver-Russell Syndrome / Q000175:diagnosis / Q000235:genetics*
chemical_list: C493964:CDKN1C protein, human; D050761:Cyclin-Dependent Kinase Inhibitor p57; C485621:KCNQ1OT1 long non-coding RNA, human; D024642:Potassium Channels, Voltage-Gated; D007335:Insulin-Like Growth Factor II