De Novo Duplication of 11p15 Associated With Congenital Diaphragmatic Hernia

Background: Congenital diaphragmatic hernia (CDH) is a rare defect of the diaphragm commonly associated with high morbidity and mortality due to lung hypoplasia and pulmonary hypertension. Although in 70% of patients the etiology of a CDH remains unknown, a multitude of causative chromosomal aberrat...

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Main Authors: Gabriel C. Dworschak, Hartmut Engels, Jessica Becker, Lukas Soellner, Thomas Eggermann, Florian Kipfmueller, Andreas Müller, Heiko Reutter, Martina Kreiß
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-04-01
Series:Frontiers in Pediatrics
Subjects:
Online Access:http://journal.frontiersin.org/article/10.3389/fped.2018.00116/full
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author Gabriel C. Dworschak
Gabriel C. Dworschak
Hartmut Engels
Jessica Becker
Lukas Soellner
Thomas Eggermann
Florian Kipfmueller
Andreas Müller
Heiko Reutter
Heiko Reutter
Martina Kreiß
author_facet Gabriel C. Dworschak
Gabriel C. Dworschak
Hartmut Engels
Jessica Becker
Lukas Soellner
Thomas Eggermann
Florian Kipfmueller
Andreas Müller
Heiko Reutter
Heiko Reutter
Martina Kreiß
author_sort Gabriel C. Dworschak
collection DOAJ
description Background: Congenital diaphragmatic hernia (CDH) is a rare defect of the diaphragm commonly associated with high morbidity and mortality due to lung hypoplasia and pulmonary hypertension. Although in 70% of patients the etiology of a CDH remains unknown, a multitude of causative chromosomal aberrations has been identified.Case presentation: We describe the first case of isolated 11p15 duplication with CDH. The 18.6 Mb large duplication affected 285 RefSeq genes and included the Beckwith–Wiedemann (BWS)-associated imprinting control region 2 (ICR2, KCNQ1OT1 TSS DMR), whereas the ICR1 (H19 TSS DMR) was not affected. We were able to demonstrate de novo occurrence of the duplication. The paternal origin of the chromosomal material was detected by methylation testing the ICR2. Corresponding to other patients with duplications of the paternal ICR2 copy, a BWS phenotype is not present.Conclusions: The patient presented here together with the review of four other cases from the literature indicate an association between duplications of the chromosomal region 11p15 and developmental defects of the diaphragm. Thus, we suggest duplications of 11p15 as a rare cause of CDH. This association may or may not appear in the context of BWS depending on the extent of the duplication and the imprinting status. Hence, a genetic workup should be performed in patients with CDH, particularly when other abnormalities are noted.
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spelling doaj.art-e7968bba51c1455b9b0971561a0cb45f2022-12-22T00:59:43ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602018-04-01610.3389/fped.2018.00116360191De Novo Duplication of 11p15 Associated With Congenital Diaphragmatic HerniaGabriel C. Dworschak0Gabriel C. Dworschak1Hartmut Engels2Jessica Becker3Lukas Soellner4Thomas Eggermann5Florian Kipfmueller6Andreas Müller7Heiko Reutter8Heiko Reutter9Martina Kreiß10Institute of Human Genetics, University of Bonn, Bonn, GermanyDepartment of Pediatrics, Children's Hospital, University of Bonn, Bonn, GermanyInstitute of Human Genetics, University of Bonn, Bonn, GermanyInstitute of Human Genetics, University of Bonn, Bonn, GermanyInstitute of Human Genetics, RWTH Aachen, Aachen, GermanyInstitute of Human Genetics, RWTH Aachen, Aachen, GermanyDepartment of Neonatology and Pediatric Intensive Care, Children's Hospital, University of Bonn, Bonn, GermanyDepartment of Neonatology and Pediatric Intensive Care, Children's Hospital, University of Bonn, Bonn, GermanyInstitute of Human Genetics, University of Bonn, Bonn, GermanyDepartment of Neonatology and Pediatric Intensive Care, Children's Hospital, University of Bonn, Bonn, GermanyInstitute of Human Genetics, University of Bonn, Bonn, GermanyBackground: Congenital diaphragmatic hernia (CDH) is a rare defect of the diaphragm commonly associated with high morbidity and mortality due to lung hypoplasia and pulmonary hypertension. Although in 70% of patients the etiology of a CDH remains unknown, a multitude of causative chromosomal aberrations has been identified.Case presentation: We describe the first case of isolated 11p15 duplication with CDH. The 18.6 Mb large duplication affected 285 RefSeq genes and included the Beckwith–Wiedemann (BWS)-associated imprinting control region 2 (ICR2, KCNQ1OT1 TSS DMR), whereas the ICR1 (H19 TSS DMR) was not affected. We were able to demonstrate de novo occurrence of the duplication. The paternal origin of the chromosomal material was detected by methylation testing the ICR2. Corresponding to other patients with duplications of the paternal ICR2 copy, a BWS phenotype is not present.Conclusions: The patient presented here together with the review of four other cases from the literature indicate an association between duplications of the chromosomal region 11p15 and developmental defects of the diaphragm. Thus, we suggest duplications of 11p15 as a rare cause of CDH. This association may or may not appear in the context of BWS depending on the extent of the duplication and the imprinting status. Hence, a genetic workup should be performed in patients with CDH, particularly when other abnormalities are noted.http://journal.frontiersin.org/article/10.3389/fped.2018.00116/fullcongenital diaphragmatic herniaCDHBeckwith-Wiedemann syndromeBWS11p15 duplicationpartial trisomy
spellingShingle Gabriel C. Dworschak
Gabriel C. Dworschak
Hartmut Engels
Jessica Becker
Lukas Soellner
Thomas Eggermann
Florian Kipfmueller
Andreas Müller
Heiko Reutter
Heiko Reutter
Martina Kreiß
De Novo Duplication of 11p15 Associated With Congenital Diaphragmatic Hernia
Frontiers in Pediatrics
congenital diaphragmatic hernia
CDH
Beckwith-Wiedemann syndrome
BWS
11p15 duplication
partial trisomy
title De Novo Duplication of 11p15 Associated With Congenital Diaphragmatic Hernia
title_full De Novo Duplication of 11p15 Associated With Congenital Diaphragmatic Hernia
title_fullStr De Novo Duplication of 11p15 Associated With Congenital Diaphragmatic Hernia
title_full_unstemmed De Novo Duplication of 11p15 Associated With Congenital Diaphragmatic Hernia
title_short De Novo Duplication of 11p15 Associated With Congenital Diaphragmatic Hernia
title_sort de novo duplication of 11p15 associated with congenital diaphragmatic hernia
topic congenital diaphragmatic hernia
CDH
Beckwith-Wiedemann syndrome
BWS
11p15 duplication
partial trisomy
url http://journal.frontiersin.org/article/10.3389/fped.2018.00116/full
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