title: Infants with Bochdalek diaphragmatic hernia: sibling precurrence and monozygotic twin discordance in a hospital-based malformation surveillance program.
abstract: Congenital diaphragmatic hernia (CDH) is a common and often devastating birth defect. In order to learn more about possible genetic causes, we reviewed and classified 203 cases of the Bochdalek hernia type identified through the Brigham and Women's Hospital (BWH) Active Malformation Surveillance Program over a 28-year period. Phenotypically, 55% of the cases had isolated CDH, and 45% had complex CDH defined as CDH in association with additional major malformations or as part of a syndrome. When classified according to likely etiology, 17% had a Recognized Genetic etiology for their CDH, while the remaining 83% had No Apparent Genetic etiology. Detailed analysis using this largest cohort of consecutively collected cases of CDH showed low precurrence among siblings. Additionally, there was no concordance for CDH among five monozygotic twin pairs. These findings, in conjunction with previous reports of de novo dominant mutations in patients with CDH, suggest that new mutations may be an important mechanism responsible for CDH. The twin data also raise the possibility that epigenetic abnormalities contribute to the development of CDH.
authors.affiliation: Genetics and Teratology, MassGeneral Hospital for Children, Boston, Massachusetts, USA. Barbara.pober@childrens.harvard.edu
authors.forename: Barbara R
authors.initials: BR
authors.lastname: Pober
authors.forename: Angela
authors.initials: A
authors.lastname: Lin
authors.forename: Meaghan
authors.initials: M
authors.lastname: Russell
authors.forename: Kate G
authors.initials: KG
authors.lastname: Ackerman
authors.forename: Sharmila
authors.initials: S
authors.lastname: Chakravorty
authors.forename: Bernarda
authors.initials: B
authors.lastname: Strauss
authors.forename: Marie Noel
authors.initials: MN
authors.lastname: Westgate
authors.forename: Jay
authors.initials: J
authors.lastname: Wilson
authors.forename: Patricia K
authors.initials: PK
authors.lastname: Donahoe
authors.forename: Lewis B
authors.initials: LB
authors.lastname: Holmes
mesh_terms: D002675:Child, Preschool; D002869:Chromosome Aberrations; D004200:Diseases in Twins / Q000235:genetics; D005260:Female; D005333:Fetus; D006306:Health Surveys; D006548:Hernia, Diaphragmatic / Q000145:classification / Q000235:genetics*; D065630:Hernias, Diaphragmatic, Congenital; D006761:Hospitals / Q000706:statistics & numerical data; D006801:Humans; D007223:Infant; D008297:Male; D012196:Review Literature as Topic; D035781:Siblings; D014430:Twins, Monozygotic / Q000235:genetics