Genetics of congenital diaphragmatic hernia

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
Seminars in Pediatric Surgery (Impact Factor: 2.22). 06/2007; 16(2):88-93. DOI: 10.1053/j.sempedsurg.2007.01.003
Source: PubMed


Congenital diaphragmatic hernia (CDH) is a common structural birth defect that affects approximately 1 in 2500 live births. Although the exact etiology of most cases of CDH remains unknown, it is becoming increasingly clear that genetic factors play an important role in many cases of CDH. In this paper, we review critical findings in the areas of clinical and basic research that highlight the importance of genetics in the development of CDH. We also provide practical information that can aid physicians and surgeons as they evaluate and care for patients with isolated, nonisolated, and syndromic forms of CDH and their families.

1 Read
  • [Show abstract] [Hide abstract]
    ABSTRACT: Morgagni hernia (MH) is a congenital herniation of the abdominal organs through the subcostosternal portion of the diaphragm. It is a rare type of diaphragmatic hernia that has been associated with other congenital anomalies. The purpose of this clinical review was to determine the incidence of associated anomalies in patients with MH at a major pediatric referral center. The medical records of all patients with the diagnosis of MH were reviewed retrospectively between 1983 and 2006. The age, sex, side of herniation, presenting symptoms and signs, associated anomalies, radiologic features, intraoperative findings, postoperative course, complications, and mortality were recorded. There were 11 males and 5 females. The average age of the patients was 34.5 months (range 2 months-14 years). Twelve patients (75%) had at least one associated congenital malformation and eight (66.6%) of them had multiple anomalies. Six (37.5%) patients had a chromosomal anomaly, Down's syndrome in five and Turner syndrome in one. MH has a high incidence of associated congenital malformations.
    Pediatric Surgery International 12/2007; 23(11):1101-3. DOI:10.1007/s00383-007-2011-x · 1.00 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To evaluate the impact of recent research on the management of congenital diaphragmatic hernia in the light of new theories on embryological development, earlier antenatal diagnosis, fetal and postnatal interventions together with advances in perinatal intensive care. The year 2007 provided in excess of 200 publications that address various aspects of congenital diaphragmatic hernia. The genetic basis and the causes of pulmonary hypoplasia at the molecular level are slowly being unravelled. Fetal MRI of lung volume, lung-head ratio, liver position and size of diaphragmatic defect have all been evaluated as early predictors of outcome and with a view to prenatal counselling. The impact of fetal interventions such as fetal endoluminal tracheal occlusion, the mode of delivery, the surgical techniques and agents for treating pulmonary hypertension were evaluated. The influence of associated anomalies and therapeutic interventions on the outcome and quality of life of survivors continue to be appraised. Deferred surgery after stabilization with gentle ventilation and reversal of pulmonary hypertension remain the cornerstones of management. Optimal presurgery and postsurgery ventilatory settings remain unproven. Continued improvement in neonatal intensive care raises the bar against which any intervention such as fetal endoluminal tracheal occlusion and extracorporeal membrane oxygenation will be judged.
    Current opinion in anaesthesiology 07/2008; 21(3):323-31. DOI:10.1097/ACO.0b013e3282f9e214 · 1.98 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Congenital diaphragmatic hernia (CDH) is a life threatening birth defect. Most of the genetic factors that contribute to the development of CDH remain unidentified. To identify genomic alterations that contribute to the development of diaphragmatic defects. A cohort of 45 unrelated patients with CDH or diaphragmatic eventrations was screened for genomic alterations by array comparative genomic hybridisation or single nucleotide polymorphism based copy number analysis. Genomic alterations that were likely to have contributed to the development of CDH were identified in 8 patients. Inherited deletions of ZFPM2 were identified in 2 patients with isolated diaphragmatic defects and a large de novo 8q deletion overlapping the same gene was found in a patient with non-isolated CDH. A de novo microdeletion of chromosome 1q41q42 and two de novo microdeletions on chromosome 16p11.2 were identified in patients with non-isolated CDH. Duplications of distal 11q and proximal 13q were found in a patient with non-isolated CDH and a de novo single gene deletion of FZD2 was identified in a patient with a partial pentalogy of Cantrell phenotype. Haploinsufficiency of ZFPM2 can cause dominantly inherited isolated diaphragmatic defects with incomplete penetrance. These data define a new minimal deleted region for CDH on 1q41q42, provide evidence for the existence of CDH related genes on chromosomes 16p11.2, 11q23-24 and 13q12, and suggest a possible role for FZD2 and Wnt signalling in pentalogy of Cantrell phenotypes. These results demonstrate the clinical utility of screening for genomic alterations in individuals with both isolated and non-isolated diaphragmatic defects.
    Journal of Medical Genetics 05/2011; 48(5):299-307. DOI:10.1136/jmg.2011.089680 · 6.34 Impact Factor
Show more