Silver-Russell syndrome and Beckwith-Wiedemann syndrome phenotypes associated with 11p duplication in a single family

Pediatr Dev Pathol. Jul-Aug 2010;13(4):326-30. doi: 10.2350/09-07-0686-CR.1.

Abstract

Genomic imprinting is an epigenetic phenomenon resulting in differential expression of maternal and paternal alleles of a subset of genes. In the mouse, mutation of imprinted genes often results in contrasting phenotypes, depending on parental origin. The overgrowth-associated Beckwith-Wiedemann syndrome (BWS) and the growth restriction-associated Silver-Russell syndrome (SRS) have been linked with a variety of epigenetic and genetic defects affecting a cluster of imprinted genes at chromosome 11p15.5. Paternally derived and maternally derived 11p15.5 duplications represent infrequent findings in BWS and SRS, respectively. Here, we report a case in which a 6.5 Mb duplication of 11p15.4-pter resulted in SRS and BWS phenotypes in a child and her mother, respectively. Molecular analyses demonstrated that the duplication involved the maternal chromosome 11p15 in the child and the paternal chromosome 11p15 in the mother. This observation provides a direct demonstration that SRS and BWS represent specular images, both at the clinical and molecular levels.

Publication types

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

MeSH terms

  • Adult
  • Beckwith-Wiedemann Syndrome / drug therapy
  • Beckwith-Wiedemann Syndrome / genetics*
  • Beckwith-Wiedemann Syndrome / pathology
  • Child, Preschool
  • Chromosomes, Human, Pair 11 / genetics*
  • Comparative Genomic Hybridization
  • DNA Methylation
  • Female
  • Gene Duplication*
  • Genomic Imprinting*
  • Human Growth Hormone / therapeutic use
  • Humans
  • Mothers*
  • Phenotype
  • Silver-Russell Syndrome / drug therapy
  • Silver-Russell Syndrome / genetics*
  • Silver-Russell Syndrome / pathology
  • Uniparental Disomy

Substances

  • Human Growth Hormone