Pober Barbara R, Lin Angela, Russell Meaghan, Ackerman Kate G, Chakravorty Sharmila, Strauss Bernarda, Westgate Marie Noel, Wilson Jay, Donahoe Patricia K, Holmes Lewis B
Genetics and Teratology, MassGeneral Hospital for Children, Boston, Massachusetts, USA.
Am J Med Genet A. 2005 Oct 1;138A(2):81-8. doi: 10.1002/ajmg.a.30904.
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.
先天性膈疝（CDH）是一种常见且往往具有严重影响的出生缺陷。为了更多地了解可能的遗传病因，我们回顾并分类了在28年期间通过布莱根妇女医院（BWH）主动畸形监测项目确定的203例波氏疝类型病例。从表型上看，55%的病例为孤立性CDH，45%为复杂性CDH，定义为与其他主要畸形相关的CDH或作为综合征的一部分。根据可能的病因分类时，17%的病例其CDH有公认的遗传病因，而其余83%没有明显的遗传病因。使用这一连续收集的最大CDH病例队列进行的详细分析显示，兄弟姐妹中的复发率较低。此外，五对同卵双胞胎中没有CDH一致性。这些发现，结合先前关于CDH患者新发显性突变的报道，表明新突变可能是导致CDH的重要机制。双胞胎数据也增加了表观遗传异常导致CDH发生的可能性。
