title: Mild Beckwith-Wiedemann and severe long-QT syndrome due to deletion of the imprinting center 2 on chromosome 11p.
abstract: We report on a young woman admitted to our Cardiology Unit because of an episode of cardiac arrest related to a long-QT syndrome (LQTS). This manifestation was part of a broader phenotype, which was recognized as a mild form of Beckwith-Wiedemann syndrome (BWS). Molecular analysis confirmed the diagnosis of BWS owing to a maternally inherited deletion of the centromeric imprinting center, or ICR2, an extremely rare genetic mechanism in BWS. The deletion interval (198 kb) also included exons 11-16 of the KCNQ1 gene, known to be responsible for LQTS at locus LQT1. No concomitant mutations were found in any other of the known LQT genes. The proposita's mother carries the same deletion in her paternal chromosome and shows manifestations of the Silver-Russell syndrome (SRS). This report describes the smallest BWS-causing ICR2 deletion and provides the first evidence that a paternal deletion of ICR2 leads to a SRS-like phenotype. In addition, our observation strongly suggests that in cases of LQTS due to mutation of the KCNQ1 gene (LQT1), an accurate clinical genetic evaluation should be done in order to program the most appropriate genetic tests.
authors.affiliation: Istituto di Genetica Medica, Università Cattolica S. Cuore, Roma, Italy.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Gurrieri
authors.forename: Marcella
authors.initials: M
authors.lastname: Zollino
authors.forename: Antonio
authors.initials: A
authors.lastname: Oliva
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Pascali
authors.forename: Daniela
authors.initials: D
authors.lastname: Orteschi
authors.forename: Roberta
authors.initials: R
authors.lastname: Pietrobono
authors.forename: Antonella
authors.initials: A
authors.lastname: Camporeale
authors.forename: Monica
authors.initials: M
authors.lastname: Coll Vidal
authors.forename: Sara
authors.initials: S
authors.lastname: Partemi
authors.forename: Ramon
authors.initials: R
authors.lastname: Brugada
authors.forename: Fulvio
authors.initials: F
authors.lastname: Bellocci
authors.forename: Giovanni
authors.initials: G
authors.lastname: Neri
mesh_terms: D001506:Beckwith-Wiedemann Syndrome / Q000175:diagnosis* / Q000235:genetics; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D005260:Female; D018392:Genomic Imprinting; D006801:Humans; D008133:Long QT Syndrome / Q000175:diagnosis* / Q000235:genetics; D017384:Sequence Deletion; D055815:Young Adult