title: Congenital hyperinsulinism in an infant with paternal uniparental disomy on chromosome 11p15: few clinical features suggestive of Beckwith-Wiedemann syndrome.
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.
authors.affiliation: Department of Pediatrics, Akita University Graduate School of Medicine, Akita 010-8543, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Adachi
authors.forename: Ikuko
authors.initials: I
authors.lastname: Takahashi
authors.forename: Ken
authors.initials: K
authors.lastname: Higashimoto
authors.forename: Satoko
authors.initials: S
authors.lastname: Tsuchida
authors.forename: Atsuko
authors.initials: A
authors.lastname: Noguchi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tamura
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Arai
authors.forename: Tomoo
authors.initials: T
authors.lastname: Ito
authors.forename: Michiya
authors.initials: M
authors.lastname: Masue
authors.forename: Hironori
authors.initials: H
authors.lastname: Nishibori
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takahashi
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Soejima
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000235:genetics; D001506:Beckwith-Wiedemann Syndrome / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D044903:Congenital Hyperinsulinism / Q000235:genetics / Q000517:prevention & control; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D006869:Hydronephrosis / Q000209:etiology / Q000517:prevention & control; D007003:Hypoglycemia / Q000209:etiology / Q000517:prevention & control; D007231:Infant, Newborn; D007329:Insulin Antagonists / Q000008:administration & dosage / Q000627:therapeutic use; D009030:Mosaicism; D015282:Octreotide / Q000008:administration & dosage / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D024661:Potassium Channels, Inwardly Rectifying / Q000737:chemistry / Q000235:genetics; D011955:Receptors, Drug / Q000737:chemistry / Q000235:genetics; D012720:Severity of Illness Index; D064233:Sulfonylurea Receptors; D016896:Treatment Outcome; D024182:Uniparental Disomy / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology
chemical_list: D018528:ATP-Binding Cassette Transporters; D007329:Insulin Antagonists; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D015282:Octreotide