Somatic overgrowth associated with overexpression of insulin-like growth factor II

Nat Med. 1996 Mar;2(3):311-6. doi: 10.1038/nm0396-311.


Overexpression of the normally imprinted fetal insulin-like growth factor II (IGF2) has been implicated in the pathogenesis of the cancer-predisposing Beckwith-Wiedemann syndrome (BWS). We have detected constitutional relaxation of imprinting of IGF2 in four children with somatic overgrowth who do not show diagnostic features of BWS. Three children showed constitutional abnormalities of H19 methylation. All four children showed nephromegaly and two developed Wilms' tumors. Gene methylation is known to be associated with gene silencing, and three children showed constitutional abnormalities of H19 gene methylation. Disruption of H19 methylation, and concomitant relaxation of IGF2 imprinting, provides another mechanism that can increase IGF2 expression in children with overgrowth. The accumulated data on normal and pathologic IGF2 expression are now sufficient to define an entity, "IGF2 overgrowth disorder," of which BWS may be one extreme manifestation. These findings have broad implications for the characterization of idiopathic overgrowth.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Beckwith-Wiedemann Syndrome / etiology
  • Beckwith-Wiedemann Syndrome / genetics*
  • Beckwith-Wiedemann Syndrome / pathology
  • Child
  • Child, Preschool
  • DNA Primers
  • Female
  • Gene Expression
  • Genomic Imprinting
  • Growth Disorders / etiology
  • Growth Disorders / genetics*
  • Growth Disorders / metabolism
  • Humans
  • Infant
  • Insulin-Like Growth Factor II / genetics*
  • Insulin-Like Growth Factor II / metabolism
  • Kidney / pathology
  • Kidney Neoplasms / etiology
  • Kidney Neoplasms / genetics
  • Male
  • Methylation
  • Molecular Sequence Data
  • Mosaicism
  • Muscle Proteins / chemistry
  • Muscle Proteins / genetics
  • Promoter Regions, Genetic
  • RNA, Long Noncoding
  • RNA, Untranslated*
  • Wilms Tumor / etiology
  • Wilms Tumor / genetics


  • DNA Primers
  • H19 long non-coding RNA
  • Muscle Proteins
  • RNA, Long Noncoding
  • RNA, Untranslated
  • Insulin-Like Growth Factor II