KEGG   DISEASE: H00713Help
Entry
H00713                      Disease                                

Name
Beckwith-Wiedemann syndrome
Description
Beckwith-Wiedemann syndrome (BWS) is an imprinting disorder characterized by overgrowth, tumor predisposition, and congenital malformations. It is associated with genetic or epigenetic abnormalities in a cluster of imprinted genes found within a genomic region of approximately one megabase on chromosome 11p15. The imprinted region 11p15 is separated into two domains, with each domain regulated by a functionally independent imprinting control regions (ICR). The centromeric ICR2 regulates the expression of CDKN1C, KCNQ1, and further genes. The majority of cases of BWS show hypomethylation in the ICR2 or mutations in the ICR2-regulated CDKN1C gene. In intron 10 of the KCNQ1 locus, the untranslated KCNQ1OT1 RNA is encoded. KCNQ10T1 is expressed by the paternal allele and probably represses realization of the CDKN1C gene. In the telomeric ICR1, hypermethylation of the H19 promoter and loss of imprinting of IGF2 have been reported in a small fraction of patients with BWS. A few BWS cases could be related to NSD1 deletions or mutations.
Category
Developmental disorder
BRITE hierarchy
Pathway
Cell cycle
Gene
CDKN1C [HSA:1028] [KO:K09993]
KCNQ10T1 [HSA:10984]
H19 [HSA:283120]
IGF2 [HSA:3481] [KO:K13769]
NSD1 [HSA:64324] [KO:K15588]
Comment
BWS and the growth retardation disorder Russell-Silver syndrome [DS:H00713] present two genetically and clinically opposite clinical pictures.
Other DBs
ICD-10: 
MeSH: 
OMIM: 
Reference
  Authors
Choufani S, Shuman C, Weksberg R
  Title
Beckwith-Wiedemann syndrome.
  Journal
Am J Med Genet C Semin Med Genet 154C:343-54 (2010)
Reference
  Authors
Weksberg R, Smith AC, Squire J, Sadowski P
  Title
Beckwith-Wiedemann syndrome demonstrates a role for epigenetic control of normal  development.
  Journal
Hum Mol Genet 12 Spec No 1:R61-8 (2003)
Reference
  Authors
Eggermann T
  Title
Silver-Russell and Beckwith-Wiedemann syndromes: opposite (epi)mutations in 11p15 result in opposite clinical pictures.
  Journal
Horm Res 71 Suppl 2:30-5 (2009)
Reference
  Authors
Nativio R, Sparago A, Ito Y, Weksberg R, Riccio A, Murrell A
  Title
Disruption of genomic neighbourhood at the imprinted IGF2-H19 locus in Beckwith-Wiedemann syndrome and Silver-Russell syndrome.
  Journal
Hum Mol Genet 20:1363-74 (2011)
Reference
  Authors
Baujat G, Rio M, Rossignol S, Sanlaville D, Lyonnet S, Le Merrer M, Munnich A, Gicquel C, Cormier-Daire V, Colleaux L
  Title
Paradoxical NSD1 mutations in Beckwith-Wiedemann syndrome and 11p15 anomalies in  Sotos syndrome.
  Journal
Am J Hum Genet 74:715-20 (2004)

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