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Prenatal Diagnosis Mar 2022Congenital diaphragmatic hernia (CDH) is often detectable prenatally. Advances in genetic testing have made it possible to obtain a molecular diagnosis in many fetuses... (Review)
Review
Congenital diaphragmatic hernia (CDH) is often detectable prenatally. Advances in genetic testing have made it possible to obtain a molecular diagnosis in many fetuses with CDH. Here, we review the aneuploidies, copy number variants (CNVs), and single genes that have been clearly associated with CDH. We suggest that array-based CNV analysis, with or without a chromosome analysis, is the optimal test for identifying chromosomal abnormalities and CNVs in fetuses with CDH. To identify causative sequence variants, whole exome sequencing (WES) is the most comprehensive strategy currently available. Whole genome sequencing (WGS) with CNV analysis has the potential to become the most efficient and effective means of identifying an underlying diagnosis but is not yet routinely available for prenatal diagnosis. We describe how to overcome and address the diagnostic and clinical uncertainty that may remain after genetic testing, and review how a molecular diagnosis may impact recurrence risk estimations, mortality rates, and the availability and outcomes of fetal therapy. We conclude that after the prenatal detection of CDH, patients should be counseled about the possible genetic causes of the CDH, and the genetic testing modalities available to them, in accordance with generally accepted guidelines for pretest counseling in the prenatal setting.
Topics: Clinical Decision-Making; DNA Copy Number Variations; Female; Hernias, Diaphragmatic, Congenital; Humans; Pregnancy; Prenatal Diagnosis; Uncertainty
PubMed: 35037267
DOI: 10.1002/pd.6099 -
European Respiratory Review : An... Mar 2018Congenital diaphragmatic hernia (CDH) is a rare congenital anomaly characterised by a diaphragmatic defect, persistent pulmonary hypertension (PH) and lung hypoplasia.... (Review)
Review
Congenital diaphragmatic hernia (CDH) is a rare congenital anomaly characterised by a diaphragmatic defect, persistent pulmonary hypertension (PH) and lung hypoplasia. The relative contribution of these three elements can vary considerably in individual patients. Most affected children suffer primarily from the associated PH, for which the therapeutic modalities are limited and frequently not evidence based. The vascular defects associated with PH, which is characterised by increased muscularisation of arterioles and capillaries, start to develop early in gestation. Pulmonary vascular development is integrated with the development of the airway epithelium. Although our knowledge is still incomplete, the processes involved in the growth and expansion of the vasculature are beginning to be unravelled. It is clear that early disturbances of this process lead to major pulmonary growth abnormalities, resulting in serious clinical challenges and in many cases death in the newborn. Here we provide an overview of the current molecular pathways involved in pulmonary vascular development. Moreover, we describe the abnormalities associated with CDH and the potential therapeutic approaches for this severe abnormality.
Topics: Animals; Arterioles; Capillaries; Hemodynamics; Hernias, Diaphragmatic, Congenital; Humans; Hypertension, Pulmonary; Lung; Neovascularization, Physiologic; Prognosis; Pulmonary Circulation; Risk Factors; Signal Transduction
PubMed: 29367409
DOI: 10.1183/16000617.0104-2017 -
Seminars in Pediatric Surgery Jun 2017Identification of CDH infant populations at high risk for mortality postnatally may help to develop targeted care strategies, guide discussions surrounding palliation... (Review)
Review
Identification of CDH infant populations at high risk for mortality postnatally may help to develop targeted care strategies, guide discussions surrounding palliation and contribute to standardizing reporting and benchmarking, so that care strategies at different centers can be compared. Clinical prediction rules are evidence-based tools that combine multiple predictors to estimate the probability that a particular outcome in an individual patient will occur. In CDH, a suitable clinical prediction rule can stratify high- and low-risk populations and provide the ability to tailor management strategies based on severity. The ideal prediction tool for infants born with CDH would be validated in a large population, generalizable, easily applied in a clinical setting and would clearly discriminate patients at the highest and lowest risk of death. To date, 4 postnatal major clinical prediction rules have been published and validated in the North American CDH population. These models contain variables such as birth weight, Apgar score, blood gases, as well as measures of pulmonary hypertension, and associated anomalies. In an era of standardized care plans and population-based strategies, the appropriate selection and application of a generalizable tool to provide an opportunity for benchmarking, policy creation, and centralizing the care of high-risk populations. A well-designed clinical prediction tool remains the most practical and expedient way to achieve these goals.
Topics: Decision Support Techniques; Hernias, Diaphragmatic, Congenital; Humans; Prognosis; Regression Analysis; Risk Assessment; Survival Rate
PubMed: 28641750
DOI: 10.1053/j.sempedsurg.2017.04.010 -
Seminars in Fetal & Neonatal Medicine Dec 2014Congenital diaphragmatic hernia (CDH) is a moderately prevalent birth defect that, despite advances in neonatal care, is still a significant cause of infant death, and... (Review)
Review
Congenital diaphragmatic hernia (CDH) is a moderately prevalent birth defect that, despite advances in neonatal care, is still a significant cause of infant death, and surviving patients have significant morbidity. The goal of ongoing research to elucidate the genetic causes of CDH is to develop better treatment and ultimately prevention. CDH is a complex developmental defect that is etiologically heterogeneous. This review summarizes the recurrent genetic causes of CDH including aneuploidies, chromosome copy number variants, and single gene mutations. It also discusses strategies for genetic evaluation and genetic counseling in an era of rapidly evolving technologies in clinical genetic diagnostics.
Topics: Chromosome Aberrations; DNA Copy Number Variations; Hernias, Diaphragmatic, Congenital; Humans; Mutation
PubMed: 25447988
DOI: 10.1016/j.siny.2014.09.003 -
International Journal of Molecular... Apr 2023Epigenetic regulators such as microRNAs (miRNAs) have a key role in modulating several gene expression pathways and have a role both in lung development and function.... (Review)
Review
Epigenetic regulators such as microRNAs (miRNAs) have a key role in modulating several gene expression pathways and have a role both in lung development and function. One of the main pathogenetic determinants in patients with congenital diaphragmatic hernia (CDH) is pulmonary hypertension (PH), which is directly related to smaller lung size and pulmonary microarchitecture alterations. The aim of this review is to highlight the importance of miRNAs in CDH-related PH and to summarize the results covering this topic in animal and human CDH studies. The focus on epigenetic modulators of CDH-PH offers the opportunity to develop innovative diagnostic tools and novel treatment modalities, and provides a great potential to increase researchers' understanding of the pathophysiology of CDH.
Topics: Animals; Humans; Hernias, Diaphragmatic, Congenital; MicroRNAs; Hypertension, Pulmonary; Lung; Pulmonary Arterial Hypertension
PubMed: 37047629
DOI: 10.3390/ijms24076656 -
Nigerian Journal of Clinical Practice Apr 2022Diaphragmatic hernias can develop congenitally or secondary to trauma. Congenital diaphragmatic hernias occur with Bochdalek hernia and Morgagni hernia (MH). In this...
BACKGROUND AND AIM
Diaphragmatic hernias can develop congenitally or secondary to trauma. Congenital diaphragmatic hernias occur with Bochdalek hernia and Morgagni hernia (MH). In this study, we aimed to present laparoscopic and open surgical treatment for traumatic and congenital diaphragmatic hernias, and complications and length of hospital stay in the light of the literature.
PATIENTS AND METHODS
Twenty-two patients who were diagnosed with diaphragmatic hernia between January 2013 and January 2020 in our clinic were examined retrospectively in terms of demographic features, clinical and radiological findings, and length of hospital stay.
RESULTS
The complaints of the patients diagnosed with diaphragmatic hernia were often abdominal pain, shortness of breath, early satiety, nausea, vomiting, and abdominal distention. The mean age of the patients was 54 (19-88) years. Sixteen patients were females and six were males. Two patients were operated due to stab injury, six patients were operated due to ileus, and the remaining fourteen patients were operated due to congenital diaphragmatic hernia. Eight patients were operated under emergency conditions. The remaining patients were operated under elective conditions. The average hospital stay was 6(3-15) days. The length of hospital stay of those who underwent laparoscopic surgery was 4 (3-5) days. No patient had an exitus. All patients were discharged with healing. This rare pathology should be remembered especially in patients presenting with acute abdominal complaints accompanied by respiratory complaints.
CONCLUSION
We think that cases with MH detected incidentally should be operated laparoscopically before becoming complicated.
Topics: Abdominal Pain; Aged; Aged, 80 and over; Female; Hernia, Hiatal; Hernias, Diaphragmatic, Congenital; Humans; Laparoscopy; Male; Middle Aged; Retrospective Studies
PubMed: 35439895
DOI: 10.4103/njcp.njcp_605_20 -
International Journal of Molecular... Jun 2021Congenital diaphragmatic hernia (CDH) is a relatively common major life-threatening birth defect that results in significant mortality and morbidity depending primarily... (Review)
Review
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 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.
Topics: Diaphragm; Genetic Predisposition to Disease; Hernias, Diaphragmatic, Congenital; High-Throughput Nucleotide Sequencing; Humans; Prognosis
PubMed: 34198563
DOI: 10.3390/ijms22126353 -
American Journal of Respiratory Cell... Nov 2023
Topics: Humans; Hernias, Diaphragmatic, Congenital; NF-kappa B; Organogenesis; Signal Transduction; Lung
PubMed: 37566564
DOI: 10.1165/rcmb.2023-0258ED -
International Journal of Environmental... Sep 2022Sildenafil, a phosphodiesterase 5 inhibitor with a vasodilatory and anti-remodeling effect, has been investigated concerning various conditions during pregnancy. Per... (Review)
Review
Sildenafil, a phosphodiesterase 5 inhibitor with a vasodilatory and anti-remodeling effect, has been investigated concerning various conditions during pregnancy. Per indication, we herein review the rationale and the most relevant experimental and clinical studies, including systematic reviews and meta-analyses, when available. Indications for using sildenafil during the second and third trimester of pregnancy include maternal pulmonary hypertension, preeclampsia, preterm labor, fetal growth restriction, oligohydramnios, fetal distress, and congenital diaphragmatic hernia. For most indications, the rationale for administering prenatal sildenafil is based on limited, equivocal data from in vitro studies and rodent disease models. Clinical studies report mild maternal side effects and suggest good fetal tolerance and safety depending on the underlying pathology.
Topics: Female; Fetal Growth Retardation; Hernias, Diaphragmatic, Congenital; Humans; Hypertension, Pulmonary; Phosphodiesterase 5 Inhibitors; Pre-Eclampsia; Pregnancy; Sildenafil Citrate
PubMed: 36141480
DOI: 10.3390/ijerph191811207 -
African Journal of Paediatric Surgery :... 2021The descriptive clinical study was conducted to analyse the clinical profile as well as the outcome of congenital right diaphragmatic defects among children including... (Observational Study)
Observational Study
BACKGROUND
The descriptive clinical study was conducted to analyse the clinical profile as well as the outcome of congenital right diaphragmatic defects among children including neonates in a tertiary care referral neonatal and paediatric centre in southern Karnataka, India.
MATERIALS AND METHODS
This retrospective and prospective observational clinical study was conducted from January 2005 to August 2019, over a period of 14.7 years in a tertiary care referral neonatal and paediatric centre. Clinical characteristics and risk factors of 33 children including neonates admitted and diagnosed with congenital right diaphragmatic defects were assessed both pre- and postoperatively. Neonates and children with acquired right diaphragmatic hernia defects and the left-sided diaphragmatic defects were not included in this clinical study.
RESULTS
For statistical as well as clinical analysis, 33 study subjects were grouped into four groups, depending on the pre-operative and intraoperative findings as well as on their final diagnosis. Group I comprised right congenital diaphragmatic hernia (RCDH) (n = 18), Group II comprised RCDH with sac (n = 6), the babies with diagnosis of right diaphragmatic eventration were included in Group III (n = 7), whereas babies with other right-sided diaphragmatic hernia defects diagnosis were included in Group IV (n = 2).
CONCLUSION
Right-sided congenital diaphragmatic defects, though rare, do carry excellent survival if referred early and managed in a tertiary care neonatal and paediatric centre as that of left diaphragmatic defects.
Topics: Child; Hernias, Diaphragmatic, Congenital; Humans; India; Infant; Infant, Newborn; Retrospective Studies
PubMed: 34341195
DOI: 10.4103/ajps.AJPS_29_20