title: Congenital hyperinsulinism in children with paternal 11p uniparental isodisomy and Beckwith-Wiedemann syndrome.
abstract: BACKGROUND
  Congenital hyperinsulinism (HI) can have monogenic or syndromic causes. Although HI has long been recognised to be common in children with Beckwith-Wiedemann syndrome (BWS), the underlying mechanism is not known.
  
  
  METHODS
  We characterised the clinical features of children with both HI and BWS/11p overgrowth spectrum, evaluated the contribution of KATP channel mutations to the molecular pathogenesis of their HI and assessed molecular pathogenesis associated with features of BWS.
  
  
  RESULTS
  We identified 28 children with HI and BWS/11p overgrowth from 1997 to 2014. Mosaic paternal uniparental isodisomy for chromosome 11p (pUPD11p) was noted in 26/28 cases. Most were refractory to diazoxide treatment and half required subtotal pancreatectomies. Patients displayed a wide range of clinical features from classical BWS to only mild hemihypertrophy (11p overgrowth spectrum). Four of the cases had a paternally transmitted KATP mutation and had a much more severe HI course than patients with pUPD11p alone.
  
  
  CONCLUSIONS
  We found that patients with pUPD11p-associated HI have a persistent and severe HI phenotype compared with transient hypoglycaemia of BWS/11p overgrowth patients caused by other aetiologies. Testing for pUPD11p should be considered in all patients with persistent congenital HI, especially for those without an identified HI gene mutation.
authors.affiliation: Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA Department of Pediatrics, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Kalish
authors.affiliation: Division of Endocrinology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors.forename: Kara E
authors.initials: KE
authors.lastname: Boodhansingh
authors.affiliation: Department of Pathology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA Department of Pathology, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Tricia R
authors.initials: TR
authors.lastname: Bhatti
authors.affiliation: Department of Genetics, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Arupa
authors.initials: A
authors.lastname: Ganguly
authors.affiliation: Department of Pathology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA Department of Pathology, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Laura K
authors.initials: LK
authors.lastname: Conlin
authors.affiliation: Division of Endocrinology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors.forename: Susan A
authors.initials: SA
authors.lastname: Becker
authors.affiliation: Division of Endocrinology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Givler
authors.affiliation: Department of Genetics, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Lindsey
authors.initials: L
authors.lastname: Mighion
authors.affiliation: Department of Pediatrics, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA Division of Endocrinology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Palladino
authors.affiliation: Department of Surgery, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA Department of Surgery, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: N Scott
authors.initials: NS
authors.lastname: Adzick
authors.affiliation: Department of Pediatrics, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA Division of Endocrinology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors.forename: Diva D
authors.initials: DD
authors.lastname: De León
authors.affiliation: Department of Pediatrics, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA Division of Endocrinology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Stanley
authors.affiliation: Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA Department of Pediatrics, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Deardorff
mesh_terms: D001506:Beckwith-Wiedemann Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D002880:Chromosomes, Human, Pair 11; D044903:Congenital Hyperinsulinism / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D007223:Infant; D054086:KATP Channels / Q000235:genetics; D008297:Male; D009154:Mutation; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D024182:Uniparental Disomy
chemical_list: D054086:KATP Channels
keywords: Endocrinology; Epigenetics; Genetics