scholarly journals Management of Congenital Diaphragmatic Hernia (CDH): Role of Molecular Genetics

2021 ◽  
Vol 22 (12) ◽  
pp. 6353
Author(s):  
Giulia Cannata ◽  
Chiara Caporilli ◽  
Federica Grassi ◽  
Serafina Perrone ◽  
Susanna Esposito
Keyword(s):  
Congenital Diaphragmatic Hernia ◽  
Diaphragmatic Hernia ◽  
De Novo ◽  
Current Knowledge ◽  
Lung Hypoplasia ◽  
Cellular Mechanisms ◽  
Major Life ◽  
Mortality And Morbidity ◽  
Functional Studies ◽  
Life Threatening

Congenital diaphragmatic hernia (CDH) is a relatively common major life-threatening birth defect that results in significant mortality and morbidity depending primarily on lung hypoplasia, persistent pulmonary hypertension, and cardiac dysfunction. Despite its clinical relevance, CDH multifactorial etiology is still not completely understood. We reviewed current knowledge on normal diaphragm development and summarized genetic mutations and related pathways as well as cellular mechanisms involved in CDH. Our literature analysis showed that the discovery of harmful de novo variants in the fetus could constitute an important tool for the medical team during pregnancy, counselling, and childbirth. A better insight into the mechanisms regulating diaphragm development and genetic causes leading to CDH appeared essential to the development of new therapeutic strategies and evidence-based genetic counselling to parents. Integrated sequencing, development, and bioinformatics strategies could direct future functional studies on CDH; could be applied to cohorts and consortia for CDH and other birth defects; and could pave the way for potential therapies by providing molecular targets for drug discovery.

Tetralogy of Fallot with congenital diaphragmatic hernia and left lung hypoplasia: assessment of the adequacy of the peripheral pulmonary vascular growth after hernia repair

2011 ◽  
Vol 22 (2) ◽  
pp. 235-238 ◽  
Author(s):  
Hong Ju Shin ◽  
Won Kyoung Jhang ◽  
Tae Jin Yun
Keyword(s):  
Congenital Diaphragmatic Hernia ◽  
Tetralogy Of Fallot ◽  
Diaphragmatic Hernia ◽  
Left Lung ◽  
Lung Hypoplasia ◽  
Vascular Growth ◽  
Threatening Condition ◽  
Central Pulmonary Artery ◽  
Life Threatening ◽  
Vascular Beds

AbstractCongenital diaphragmatic hernia is a life-threatening condition frequently associated with various congenital cardiac diseases. In congenital diaphragmatic hernia associated with tetralogy of Fallot, central pulmonary artery size of the affected side may not reflect the capacitance of peripheral pulmonary vascular beds. We report a case of congenital diaphragmatic hernia associated with tetralogy of Fallot, which was repaired after assessing the adequacy of the pulmonary vascular beds by intra-operative pulmonary blood flow study.

scholarly journals Genetics of diaphragmatic hernia

2021 ◽  
Author(s):  
Yannick Schreiner ◽  
Thomas Schaible ◽  
Neysan Rafat
Keyword(s):  
Pulmonary Hypertension ◽  
Clinical Outcome ◽  
Congenital Diaphragmatic Hernia ◽  
Diaphragmatic Hernia ◽  
Congenital Malformations ◽  
Lung Hypoplasia ◽  
Complex Phenotype ◽  
Life Threatening ◽  
Major Congenital Malformations ◽  
Very High

AbstractCongenital diaphragmatic hernia (CDH) is a life-threatening malformation characterised by failure of diaphragmatic development with lung hypoplasia and persistent pulmonary hypertension of the newborn (PPHN). The incidence is 1:2000 corresponding to 8% of all major congenital malformations. Morbidity and mortality in affected newborns are very high and at present, there is no precise prenatal or early postnatal prognostication parameter to predict clinical outcome in CDH patients. Most cases occur sporadically, however, genetic causes have long been discussed to explain a proportion of cases. These range from aneuploidy to complex chromosomal aberrations and specific mutations often causing a complex phenotype exhibiting multiple malformations along with CDH. This review summarises the genetic variations which have been observed in syndromic and isolated cases of congenital diaphragmatic hernia.

Congenital Diaphragmatic Hernia: More than Just a Lung Problem

2021 ◽  
Vol 8 (4) ◽  
Author(s):  
Emam D ◽  
◽  
Van der Veeken L ◽  
El Badry A ◽  
Elattar A ◽  
...  
Keyword(s):  
Congenital Diaphragmatic Hernia ◽  
Diaphragmatic Hernia ◽  
Lung Hypoplasia ◽  
Short Term ◽  
Mortality And Morbidity ◽  
Abdominal Organs ◽  
Increased Risk ◽  
Prenatal Intervention ◽  
The Cost ◽  
Neurodevelopmental Problems

Congenital Diaphragmatic Hernia (CDH) is a rare congenital anomaly characterized by a defect in the diaphragm, which permits abdominal organs to herniate into the thorax. This causes lung hypoplasia and at birth, children with CDH experience respiratory distress and pulmonary hypertension. Despite optimal neonatal treatment, CDH is still associated with a high mortality and morbidity. In severe cases, Fetal Intervention (FETO) may alter the natural course of this disease. Herein we describe the rationale, action mechanism and technique to perform this intervention. Despite hope giving results, this technique remains investigational for left sided CDH. However, an increased survival may come at the cost of increased morbidity. Children born with CDH are at increased risk for long and short-term morbidity, including neurodevelopmental problems. Until now, there are still uncertainties about the severity and prevalence of neurologic morbidity. Furthermore, it remains uncertain if these problems are already present prenatally and if a prenatal intervention influence this.

scholarly journals Ultrasound, Echocardiography, MRI, and Genetic Analysis of a Fetus with Congenital Diaphragmatic Hernia and Partial 11q Trisomy

2017 ◽  
Vol 2017 ◽  
pp. 1-4
Author(s):  
Yolanda Fernández-Perea ◽  
Lutgardo García-Díaz ◽  
Javier Sánchez ◽  
Guillermo Antiñolo ◽  
Salud Borrego
Keyword(s):  
Prenatal Diagnosis ◽  
Genetic Analysis ◽  
Congenital Diaphragmatic Hernia ◽  
Diaphragmatic Hernia ◽  
De Novo ◽  
Partial Trisomy ◽  
Congenital Defects ◽  
Developmental Defect ◽  
Chromosome 11 ◽  
Mortality And Morbidity

Congenital diaphragmatic hernia (CDH) is a serious birth defect with a significant mortality and morbidity. The current and constant progress in ultrasound techniques has led to the improvement of the prenatal diagnosis of this malformation. CDH is a developmental defect whose etiology is heterogeneous and takes place when the pleuroperitoneal folds and septum transversum fail to converge and fuse. Survival depends on the extent of pulmonary hypoplasia and the disease may be potentially worsened by the presence of added congenital defects. 40% of CDH cases are associated with at least one additional anomaly. The ultrasound diagnosis is established with essential signs: loss of uniform echogenicity of lungs and marked mediastinal shift. We report the case of a fetus with isolated CDH diagnosed at 21 weeks of gestation by ultrasound and confirmed by RMI, whose genetic analysis of amniotic fluid cells identified a de novo partial trisomy of the long arm of chromosome 11. Different genetic causes have been associated with CDH. Moreover, it is expectable that the use of new techniques for prenatal diagnosis will reveal novel CNVs associated with CDH and will help us to estimate the recurrence risk for this defect as well as for other associated anomalies.

Possibility of application of prenatal ultrasound indexes in congenital diaphragmatic hernia in fetus to determine postnatal outcomes

2021 ◽  
Author(s):  
N.V. Mashinets
Keyword(s):  
Congenital Diaphragmatic Hernia ◽  
Diaphragmatic Hernia ◽  
Pleural Cavity ◽  
Prenatal Ultrasound ◽  
Lung Hypoplasia ◽  
Prenatal Period ◽  
Compression Index ◽  
Disease Group ◽  
Group I ◽  
Group Ii

Objectives. To assess the effectiveness of the use of prenatal ultrasound indexes in congenital diaphragmatic hernia of the fetus to determine the postnatal prognosis. Materials. The analysis of 95 observations of left-sided congenital diaphragmatic hernia of the fetus was carried out. In the prenatal period, the composition of organs displaced into the pleural cavity was determined, the heart compression index (HCI), O/E LHR according to Jani and DeKoninck, and QLI were calculated. Results. Survival rate of newborns was 57.9%, mortality rate was 42.1%. The newborns were divided into two groups depending on the outcome of the disease. Group I — surviving newborns (n = 55), group II — deceased patients (n = 40). In the analyzed groups, there were no statistical differences in the timing of delivery, birth weight of newborns, the severity of asphyxia after birth and the type of hernia. In group I, the intestinal loops and stomach were significantly more often identified in the pleural cavity in isolation, less often the liver. HCI corresponded to 1.3, Jani O/E LHR 45.7%, DeKoninck O/E LHR 38.7%, QLI 0.7. In group II, concomitant malformations, polyhydramnios and displacement of the liver into the pleural cavity were significantly more frequent. HCI was 1.5, Jani O/E LHR 38.6%, DeKoninck O/E LHR 32.0%, QLI 0.6. Conclusions. In predicting the outcome of the disease for a newborn, the most effective is a comprehensive assessment of the location of the liver, the heart compression index and the index of lung hypoplasia (O/E LHR according to Jani). The diagnostic accuracy of the method is 80%, the sensitivity is 74.4%, and the specificity is 83.3%.

scholarly journals Prenatal Diagnosis and Management of a Rare Central Tendon Defect Type of Congenital Diaphragmatic Hernia with a Massive Pericardial Effusion

2020 ◽  
Vol 2020 ◽  
pp. 1-5
Author(s):  
Inas Babic ◽  
Haifa Al-Jobair ◽  
Osama Al Towaijri ◽  
Huda Al-Shammary ◽  
Merna Atiyah ◽  
...  
Keyword(s):  
Pericardial Effusion ◽  
Congenital Diaphragmatic Hernia ◽  
Diaphragmatic Hernia ◽  
Neonatal Morbidity ◽  
Lung Hypoplasia ◽  
Defect Type ◽  
Tendon Defect ◽  
Prenatal Diagnostic ◽  
Large Pericardial Effusion ◽  
Prenatal Intervention

The central tendon defect type of congenital diaphragmatic hernia (CDH) is extremely rare and usually associated with a significant pericardial effusion. Prenatal diagnostic ultrasound features of this quite rare entity remain often overlooked or misdiagnosed. There is a dearth of literature about the role of prenatal intervention, often through an elective pericardiocentesis, for the prevention of lung hypoplasia and to decrease the overall neonatal morbidity and mortality. To the best of our knowledge, till date, there is only one case that was subjected to a prenatal intervention. Here, we present a second case of a central tendon defect type of CDH with a large pericardial effusion that was subjected to a prenatal transthoracic pericardiocentesis. Although smooth intubation and ventilation were performed immediately after birth, the infant suffered for several months from respiratory instability. Laparoscopic central tendon hernia repair was performed, and neonate was discharged home at seven months of age. Although prenatal pericardiocentesis may facilitate smoother postnatal intubation and ventilation, its broader effect on respiratory function is uncertain and still remains elusive.

scholarly journals De novo frameshift mutation inCOUP-TFII(NR2F2) in human congenital diaphragmatic hernia

2016 ◽  
Vol 170 (9) ◽  
pp. 2457-2461 ◽  
Author(s):  
Frances A. High ◽  
Pooja Bhayani ◽  
Jay M. Wilson ◽  
Carol J. Bult ◽  
Patricia K. Donahoe ◽  
...  
Keyword(s):  
Congenital Diaphragmatic Hernia ◽  
Diaphragmatic Hernia ◽  
Frameshift Mutation ◽  
De Novo

scholarly journals Cellular Origin(s) of Congenital Diaphragmatic Hernia

2021 ◽  
Vol 9 ◽  
Author(s):  
Gabriëla G. Edel ◽  
Gerben Schaaf ◽  
Rene M. H. Wijnen ◽  
Dick Tibboel ◽  
Gabrielle Kardon ◽  
...  
Keyword(s):  
Congenital Diaphragmatic Hernia ◽  
Diaphragmatic Hernia ◽  
Birth Defect ◽  
Congenital Disorder ◽  
Diaphragmatic Defect ◽  
Lung Hypoplasia ◽  
Cellular Origin ◽  
Recent Developments ◽  
Mechanical Factors

Congenital diaphragmatic hernia (CDH) is a structural birth defect characterized by a diaphragmatic defect, lung hypoplasia and structural vascular defects. In spite of recent developments, the pathogenesis of CDH is still poorly understood. CDH is a complex congenital disorder with multifactorial etiology consisting of genetic, cellular and mechanical factors. This review explores the cellular origin of CDH pathogenesis in the diaphragm and lungs and describes recent developments in basic and translational CDH research.

scholarly journals Systematic analysis of copy number variation associated with congenital diaphragmatic hernia

2018 ◽  
Vol 115 (20) ◽  
pp. 5247-5252 ◽  
Author(s):  
Qihui Zhu ◽  
Frances A. High ◽  
Chengsheng Zhang ◽  
Eliza Cerveira ◽  
Meaghan K. Russell ◽  
...  
Keyword(s):  
Congenital Diaphragmatic Hernia ◽  
Candidate Genes ◽  
Birth Defects ◽  
Diaphragmatic Hernia ◽  
Copy Number ◽  
Large Scale ◽  
De Novo ◽  
Comparative Genomic ◽  
High Morbidity ◽  
Systematic Analysis

Congenital diaphragmatic hernia (CDH), characterized by malformation of the diaphragm and hypoplasia of the lungs, is one of the most common and severe birth defects, and is associated with high morbidity and mortality rates. There is growing evidence demonstrating that genetic factors contribute to CDH, although the pathogenesis remains largely elusive. Single-nucleotide polymorphisms have been studied in recent whole-exome sequencing efforts, but larger copy number variants (CNVs) have not yet been studied on a large scale in a case control study. To capture CNVs within CDH candidate regions, we developed and tested a targeted array comparative genomic hybridization platform to identify CNVs within 140 regions in 196 patients and 987 healthy controls, and identified six significant CNVs that were either unique to patients or enriched in patients compared with controls. These CDH-associated CNVs reveal high-priority candidate genes including HLX, LHX1, and HNF1B. We also discuss CNVs that are present in only one patient in the cohort but have additional evidence of pathogenicity, including extremely rare large and/or de novo CNVs. The candidate genes within these predicted disease-causing CNVs form functional networks with other known CDH genes and play putative roles in DNA binding/transcription regulation and embryonic development. These data substantiate the importance of CNVs in the etiology of CDH, identify CDH candidate genes and pathways, and highlight the importance of ongoing analysis of CNVs in the study of CDH and other structural birth defects.

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