Congenital hyperinsulinism in an infant with paternal uniparental disomy on chromosome 11p15: few clinical features suggestive of Beckwith-Wiedemann syndrome

Endocr J. 2013;60(4):403-8. doi: 10.1507/endocrj.ej12-0242. Epub 2012 Nov 30.

Abstract

Beckwith-Wiedemann syndrome (BWS) is the most common congenital overgrowth syndrome involving tumor predisposition. BWS is caused by various epigenetic or genetic alterations that disrupt the imprinted genes on chromosome 11p15.5 and the clinical findings of BWS are highly variable. Hyperinsulinemic hypoglycemia is reported in about half of all babies with BWS. We identified an infant with diazoxide-unresponsive congenital hyperinsulinism (HI) without any apparent clinical features suggestive of BWS, but diagnosed BWS by molecular testing. The patient developed severe hyperinsulinemic hypoglycemia within a few hours after birth, with macrosomia and mild hydronephrosis. We excluded mutations in the K(ATP) channel genes on chromosome 11p15.1, but found a rare homozygous single nucleotide polymorphism (SNP) of ABCC8. Parental SNP pattern suggested paternal uniparetal disomy in this region. By microsatellite marker analysis on chromosome 11p15, we could diagnose BWS due to the mosaic of paternal uniparental disomy. Our case suggests that some HI of unknown genetic etiology could involve undiagnosed BWS with no apparent clinical features, which might be diagnosed only by molecular testing.

Publication types

  • Case Reports

MeSH terms

  • ATP-Binding Cassette Transporters / chemistry
  • ATP-Binding Cassette Transporters / genetics
  • Beckwith-Wiedemann Syndrome / diagnosis*
  • Beckwith-Wiedemann Syndrome / drug therapy
  • Beckwith-Wiedemann Syndrome / genetics
  • Beckwith-Wiedemann Syndrome / physiopathology
  • Chromosomes, Human, Pair 11 / genetics
  • Congenital Hyperinsulinism / genetics
  • Congenital Hyperinsulinism / prevention & control
  • Drug Monitoring
  • Female
  • Humans
  • Hydronephrosis / etiology
  • Hydronephrosis / prevention & control
  • Hypoglycemia / etiology
  • Hypoglycemia / prevention & control
  • Infant, Newborn
  • Insulin Antagonists / administration & dosage
  • Insulin Antagonists / therapeutic use
  • Mosaicism
  • Octreotide / administration & dosage
  • Octreotide / therapeutic use
  • Polymorphism, Single Nucleotide
  • Potassium Channels, Inwardly Rectifying / chemistry
  • Potassium Channels, Inwardly Rectifying / genetics
  • Receptors, Drug / chemistry
  • Receptors, Drug / genetics
  • Severity of Illness Index
  • Sulfonylurea Receptors
  • Treatment Outcome
  • Uniparental Disomy / diagnosis*
  • Uniparental Disomy / genetics
  • Uniparental Disomy / physiopathology

Substances

  • ATP-Binding Cassette Transporters
  • Insulin Antagonists
  • Potassium Channels, Inwardly Rectifying
  • Receptors, Drug
  • Sulfonylurea Receptors
  • Octreotide

Supplementary concepts

  • Uniparental disomy of 11