Materiały źródłowe

• #1 Congenital Diaphragmatic Hernia | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-7-1

  Congenital Diaphragmatic Hernia (CDH) is defined by the presence of an orifice in the diaphragm, more often left and posterolateral that permits the herniation of abdominal contents into the thorax. […] The etiology is unknown although clinical, genetic and experimental evidence points to disturbances in the retinoid-signaling pathway during organogenesis. […] The causes of CDH are largely unknown. Most cases are isolated, but associated malformations are often observed, sometimes as components of Pallister-Killian and Fryns, Ghersoni-Baruch, WAGR and Denys-Drash, Brachman-De Lange, Donnai-Barrow or Wolf-Hirschhorn syndromes. […] CDH occurs more often on the left side (4:1). […] The orifice in the diaphragm is caused by delayed or disturbed separation of the thoracic and abdominal compartments of the body by closure of embryonic pleuroperitoneal canals effected by growth of the post-hepatic mesenchymal plate and of the pleuroperitoneal folds.

• #2 Management of Congenital Diaphragmatic Hernia (CDH): Role of Molecular Genetics

  https://www.mdpi.com/1422-0067/22/12/6353

  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. […] CDH is thought to be multi-factorial, with genetic, environmental, and nutritional factors playing a role. […] The involvement of multiple genetic factors is suggested by recent advances in our understanding of the genetic pathways regulating normal diaphragm development and genetic mutations leading to CDH. […] Genetic contributions to CDH appeared heterogeneous. Advances in genomics, coupled with functional studies in animal models, are increasingly identifying the causes of CDH in both familial and sporadic cases.

• #3 The etiology of congenital diaphragmatic hernia: the retinoid hypothesis 20 years later | Pediatric Research

  https://www.nature.com/articles/s41390-023-02905-7

  Congenital diaphragmatic hernia (CDH) is a severe birth defect and a major cause of neonatal respiratory distress. […] Despite the significant impact of CDH, its etiology remains incompletely understood. […] The etiology of CDH is complex and remains largely unknown. […] It is generally considered that the two main factors that contribute to CDH are genetic and/or environmental. […] Approximately 30-40% of CDH cases have an identifiable genetic cause. […] Of this number, chromosomal defects account for about ~10% of CDH cases, and de novo mutations account for 10-22% of cases. […] Environmental risk factors for CDH are varied, including associations with maternal age, alcohol use, and smoking. […] One of the leading hypotheses to explain the etiology of CDH is the so-called Retinoid Hypothesis.

• #4 Congenital Diaphragmatic Hernia (CDH): What Parents Need To Know

  https://my.clevelandclinic.org/health/diseases/24308-diaphragmatic-hernia

  A congenital diaphragmatic hernia (CDH) is a birth defect (congenital disorder) that occurs during fetal development. It means that a fetus’s diaphragm isn’t fully formed or strong enough to be a muscle barrier between its belly (abdomen) and chest. That means organs can pass between them. When an organ passes through a muscle barrier, it’s called a hernia. […] Physicians don’t know the exact cause of CDH. Research suggests the following factors may play a role in its development: Genetics, Harmful environmental exposure during pregnancy, Fetal malnutrition.

• #5 The etiology of congenital diaphragmatic hernia: the retinoid hypothesis 20 years later | Pediatric Research

  https://www.nature.com/articles/s41390-023-02905-7

  Congenital diaphragmatic hernia (CDH) is a severe birth defect and a major cause of neonatal respiratory distress. […] Despite the significant impact of CDH, its etiology remains incompletely understood. […] The etiology of CDH is complex and remains largely unknown. […] It is generally considered that the two main factors that contribute to CDH are genetic and/or environmental. […] Approximately 30-40% of CDH cases have an identifiable genetic cause. […] Of this number, chromosomal defects account for about ~10% of CDH cases, and de novo mutations account for 10-22% of cases. […] Environmental risk factors for CDH are varied, including associations with maternal age, alcohol use, and smoking. […] One of the leading hypotheses to explain the etiology of CDH is the so-called Retinoid Hypothesis.

• #6 The etiology of congenital diaphragmatic hernia: the retinoid hypothesis 20 years later | Pediatric Research

  https://www.nature.com/articles/s41390-023-02905-7

  Congenital diaphragmatic hernia (CDH) is a severe birth defect and a major cause of neonatal respiratory distress. […] Despite the significant impact of CDH, its etiology remains incompletely understood. […] The etiology of CDH is complex and remains largely unknown. […] It is generally considered that the two main factors that contribute to CDH are genetic and/or environmental. […] Approximately 30-40% of CDH cases have an identifiable genetic cause. […] Of this number, chromosomal defects account for about ~10% of CDH cases, and de novo mutations account for 10-22% of cases. […] Environmental risk factors for CDH are varied, including associations with maternal age, alcohol use, and smoking. […] One of the leading hypotheses to explain the etiology of CDH is the so-called Retinoid Hypothesis.

• #7 Management of Congenital Diaphragmatic Hernia (CDH): Role of Molecular Genetics

  https://www.mdpi.com/1422-0067/22/12/6353

  The majority of CDH cases are sporadic and appear to be multifactorial. The etiology of most cases remains unknown; however, there is increasing evidence that genetic factors may play a role in the development of CDH. […] Chromosomal aberrations have been discovered as an important etiology for CDH, reported in about 10% of CDH cases and detected by routine karyotyping and chromosome microarray.

• #8 Congenital Diaphragmatic Hernia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK556076/

  The etiology of congenital diaphragmatic hernia remains unclear. It is thought to be multifactorial with genetic, environmental, and/or nutritional factors playing a role. CDH can be an isolated anomaly or associated with anomalies in other organ systems. Multiple chromosomal aberrations (deletions, aneuploidies, etc.) and single-gene mutations (GATA4, LRP2, etc.) are associated with CDH. The most frequent aneuploidies associated with CDH include trisomy 18, trisomy 13, trisomy 21, and less frequently Turner syndrome (45, X). Some of the syndromes associated with CDH include Pallister-Killian syndrome, 8p23.1 deletion syndrome, Fryns syndrome, Cornelia de Lange syndrome. Exposure to teratogenic agents like mycophenolate mofetil, allopurinol, and lithium during pregnancy is reported to be associated with CDH. […] Recently, studies indicate disturbances in the retinoid-signaling pathway as a potential cause of CDH.

• #9 Genetic causes of congenital diaphragmatic hernia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4259843/

  Congenital diaphragmatic hernia (CDH) is a complex developmental defect that is etiologically heterogeneous. […] More than 50 different genetic causes have been associated with CDH, most in non-isolated cases, but, increasingly, genetic etiologies are being identified in isolated CDH cases. […] Complete or mosaic chromosome aneuploidies, large chromosome deletions/duplications, and complex chromosome rearrangements identifiable by karyotype are present in 10-35% of CDH cases and occur at greatest frequency in non-isolated, prenatally diagnosed cases. […] Aneuploidies, CNVs and cytogenetic rearrangements involving almost all chromosomes have been described with CDH. […] The most prevalent aneuploidy associated with CDH, trisomy 18, occurs in ~25% of CDH cases. […] CDH occurs in 50% of Donnai-Barrow syndrome cases.

• #10 The etiology of congenital diaphragmatic hernia: the retinoid hypothesis 20 years later | Pediatric Research

  https://www.nature.com/articles/s41390-023-02905-7

  Congenital diaphragmatic hernia (CDH) is a severe birth defect and a major cause of neonatal respiratory distress. […] Despite the significant impact of CDH, its etiology remains incompletely understood. […] The etiology of CDH is complex and remains largely unknown. […] It is generally considered that the two main factors that contribute to CDH are genetic and/or environmental. […] Approximately 30-40% of CDH cases have an identifiable genetic cause. […] Of this number, chromosomal defects account for about ~10% of CDH cases, and de novo mutations account for 10-22% of cases. […] Environmental risk factors for CDH are varied, including associations with maternal age, alcohol use, and smoking. […] One of the leading hypotheses to explain the etiology of CDH is the so-called Retinoid Hypothesis.

• #11 Congenital Diaphragmatic Hernia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK556076/

  The etiology of congenital diaphragmatic hernia remains unclear. It is thought to be multifactorial with genetic, environmental, and/or nutritional factors playing a role. CDH can be an isolated anomaly or associated with anomalies in other organ systems. Multiple chromosomal aberrations (deletions, aneuploidies, etc.) and single-gene mutations (GATA4, LRP2, etc.) are associated with CDH. The most frequent aneuploidies associated with CDH include trisomy 18, trisomy 13, trisomy 21, and less frequently Turner syndrome (45, X). Some of the syndromes associated with CDH include Pallister-Killian syndrome, 8p23.1 deletion syndrome, Fryns syndrome, Cornelia de Lange syndrome. Exposure to teratogenic agents like mycophenolate mofetil, allopurinol, and lithium during pregnancy is reported to be associated with CDH. […] Recently, studies indicate disturbances in the retinoid-signaling pathway as a potential cause of CDH.

• #12 Congenital diaphragmatic hernia – Wikipedia

  https://en.wikipedia.org/wiki/Congenital_diaphragmatic_hernia

  Congenital diaphragmatic hernia (CDH) is a birth defect of the diaphragm. The most common type of CDH is a Bochdalek hernia; other types include Morgagni hernia, diaphragm eventration and central tendon defects of the diaphragm. Malformation of the diaphragm allows the abdominal organs to push into the chest cavity, hindering proper lung formation. […] There are genetic causes of CDH including aneuploidies, chromosome copy number variants, and single gene mutations. Research implicates a few gene mutations including LONP1 and MYRF. […] It involves three major defects: A failure of the diaphragm to completely close during development, Herniation of the abdominal contents into the chest, Pulmonary hypoplasia.

• #13 Diaphragmatic Hernias: Practice Essentials, Anatomy, Pathophysiology

  https://emedicine.medscape.com/article/934824-overview

  The etiology of CDH is largely unknown but is probably multifactorial. However, there are several reported maternal risk factors for CDH have been reported, including the following: Advanced age, Gestational diabetes, Gestational hypertension, Low body mass index (BMI), Tobacco use, Alcohol use. […] Multiple studies are currently investigating genetic factors leading to CDH; there is a known association between CDH and certain chromosomal abnormalities. An estimated 60% of CDH cases are isolated (ie, occur in healthy term pregnancies), whereas 40% are nonisolated (ie, occur in infants with an associated chromosomal or other structural anomaly). […] Abnormalities in the retinoid signaling pathway have been hypothesized to contribute to the etiology. […] The earliest link was observed when 25-40% of the offspring of rat dams fed a vitamin A-deficient diet developed CDH, and the proportion of affected pups decreased when vitamin A was reintroduced into the diet in midgestation. […] To achieve a better understanding of the underlying etiology of CDH, further research will be required.

• #14 Congenital diaphragmatic hernia: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/congenital-diaphragmatic-hernia/

  Congenital diaphragmatic hernia has many different causes. In 10 to 15 percent of affected individuals, the condition appears as a feature of a disorder that affects many body systems, called a syndrome. Donnai-Barrow syndrome, Fryns syndrome, and Pallister-Killian mosaic syndrome are among several syndromes in which congenital diaphragmatic hernia may occur. Some of these syndromes are caused by changes in single genes, and others are caused by chromosomal abnormalities that affect several genes. […] About 25 percent of individuals with congenital diaphragmatic hernia that is not associated with a known syndrome also have abnormalities of one or more major body systems. Affected body systems can include the heart, brain, skeleton, intestines, genitals, kidneys, or eyes. In these individuals, the multiple abnormalities likely result from a common underlying disruption in development that affects more than one area of the body, but the specific mechanism responsible for this disruption is not clear.

• #15 Congenital diaphragmatic hernia — Knowledge Hub

  https://www.genomicseducation.hee.nhs.uk/genotes/knowledge-hub/congenital-diaphragmatic-hernia/

  Congenital diaphragmatic hernia (CDH) occurs when the diaphragm fails to form a complete barrier between the thorax and the abdomen, leading to abdominal organs such as the bowel and stomach herniating into the thoracic cavity. […] Around 20% of cases of CDH are associated with chromosomal anomalies, most commonly trisomy 13, trisomy 18 and Pallister-Killian syndrome (tetrasomy 12p). […] Around 10% of cases are associated with other genetic syndromes. The most common of these is Fryns syndrome, an autosomal recessive condition that also presents with anophthalmia, facial cleft, micrognathia and ventriculomegaly. […] Recurrence risk is dependent on the underlying genetic or chromosomal cause. If no underlying cause is identified, and the case is found to be an isolated CDH, there is unlikely to be an increased risk in subsequent pregnancies.

• #16 Congenital Diaphragmatic Hernia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK556076/

  The etiology of congenital diaphragmatic hernia remains unclear. It is thought to be multifactorial with genetic, environmental, and/or nutritional factors playing a role. CDH can be an isolated anomaly or associated with anomalies in other organ systems. Multiple chromosomal aberrations (deletions, aneuploidies, etc.) and single-gene mutations (GATA4, LRP2, etc.) are associated with CDH. The most frequent aneuploidies associated with CDH include trisomy 18, trisomy 13, trisomy 21, and less frequently Turner syndrome (45, X). Some of the syndromes associated with CDH include Pallister-Killian syndrome, 8p23.1 deletion syndrome, Fryns syndrome, Cornelia de Lange syndrome. Exposure to teratogenic agents like mycophenolate mofetil, allopurinol, and lithium during pregnancy is reported to be associated with CDH. […] Recently, studies indicate disturbances in the retinoid-signaling pathway as a potential cause of CDH.

• #17 Congenital diaphragmatic hernia: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/congenital-diaphragmatic-hernia/

  Congenital diaphragmatic hernia has many different causes. In 10 to 15 percent of affected individuals, the condition appears as a feature of a disorder that affects many body systems, called a syndrome. Donnai-Barrow syndrome, Fryns syndrome, and Pallister-Killian mosaic syndrome are among several syndromes in which congenital diaphragmatic hernia may occur. Some of these syndromes are caused by changes in single genes, and others are caused by chromosomal abnormalities that affect several genes. […] About 25 percent of individuals with congenital diaphragmatic hernia that is not associated with a known syndrome also have abnormalities of one or more major body systems. Affected body systems can include the heart, brain, skeleton, intestines, genitals, kidneys, or eyes. In these individuals, the multiple abnormalities likely result from a common underlying disruption in development that affects more than one area of the body, but the specific mechanism responsible for this disruption is not clear.

• #18 Congenital diaphragmatic hernia — Knowledge Hub

  https://www.genomicseducation.hee.nhs.uk/genotes/knowledge-hub/congenital-diaphragmatic-hernia/

  If the case is associated with aneuploidy, the recurrence risk is around 1%. […] If the case is associated with a recessive genetic syndrome, there is a 25% recurrence risk. However, the recurrence risk would depend on the specific syndrome, and individualised counselling from the clinical genetics team would be recommended.

• #19 Congenital Diaphragmatic Hernia (CDH) | Lurie Children’s

  https://www.luriechildrens.org/en/specialties-conditions/congenital-diaphragmatic-hernia/

  The cause of fetal diaphragmatic hernia is largely unknown and usually occurs without any additional abnormalities. […] Occasionally, CDH is associated with genetic and non-genetic syndromes and genetic testing is typically recommended in all cases. […] The risk of a CDH occurring again in a future pregnancy is extremely low (1 to 2%).

• #20 Congenital diaphragmatic hernia — Knowledge Hub

  https://www.genomicseducation.hee.nhs.uk/genotes/knowledge-hub/congenital-diaphragmatic-hernia/

  If the case is associated with aneuploidy, the recurrence risk is around 1%. […] If the case is associated with a recessive genetic syndrome, there is a 25% recurrence risk. However, the recurrence risk would depend on the specific syndrome, and individualised counselling from the clinical genetics team would be recommended.

• #21 The etiology of congenital diaphragmatic hernia: the retinoid hypothesis 20 years later | Pediatric Research

  https://www.nature.com/articles/s41390-023-02905-7

  The Retinoid Hypothesis is centered on the importance of the signaling molecule retinoic acid (RA) as a potent regulator of mammalian development. […] The formulation of the Retinoid Hypothesis had a significant impact on the field and its direction of research. […] The Retinoid Hypothesis was based on research dating back to the 1940s, drawing together several threads of evidence to justify the notion that altered retinoid signaling may cause CDH. […] The balance of this evidence led the authors to conclude that altered retinoid signaling may be a contributing factor in the etiology of CDH. […] The strongest evidence linking RA signaling and CDH in humans exists for STRA6, RALDH2, and RARB. […] Mutations in this gene cause a variety of different phenotypes, including tetralogy of Fallot, absent thymus, kidney defects, as well as diaphragm eventration/Bochdalek CDH.

• #22 Diaphragmatic Hernias: Practice Essentials, Anatomy, Pathophysiology

  https://emedicine.medscape.com/article/934824-overview

  The etiology of CDH is largely unknown but is probably multifactorial. However, there are several reported maternal risk factors for CDH have been reported, including the following: Advanced age, Gestational diabetes, Gestational hypertension, Low body mass index (BMI), Tobacco use, Alcohol use. […] Multiple studies are currently investigating genetic factors leading to CDH; there is a known association between CDH and certain chromosomal abnormalities. An estimated 60% of CDH cases are isolated (ie, occur in healthy term pregnancies), whereas 40% are nonisolated (ie, occur in infants with an associated chromosomal or other structural anomaly). […] Abnormalities in the retinoid signaling pathway have been hypothesized to contribute to the etiology. […] The earliest link was observed when 25-40% of the offspring of rat dams fed a vitamin A-deficient diet developed CDH, and the proportion of affected pups decreased when vitamin A was reintroduced into the diet in midgestation. […] To achieve a better understanding of the underlying etiology of CDH, further research will be required.

• #23 Diaphragmatic Hernias: Practice Essentials, Anatomy, Pathophysiology

  https://emedicine.medscape.com/article/934824-overview

  The etiology of CDH is largely unknown but is probably multifactorial. However, there are several reported maternal risk factors for CDH have been reported, including the following: Advanced age, Gestational diabetes, Gestational hypertension, Low body mass index (BMI), Tobacco use, Alcohol use. […] Multiple studies are currently investigating genetic factors leading to CDH; there is a known association between CDH and certain chromosomal abnormalities. An estimated 60% of CDH cases are isolated (ie, occur in healthy term pregnancies), whereas 40% are nonisolated (ie, occur in infants with an associated chromosomal or other structural anomaly). […] Abnormalities in the retinoid signaling pathway have been hypothesized to contribute to the etiology. […] The earliest link was observed when 25-40% of the offspring of rat dams fed a vitamin A-deficient diet developed CDH, and the proportion of affected pups decreased when vitamin A was reintroduced into the diet in midgestation. […] To achieve a better understanding of the underlying etiology of CDH, further research will be required.

• #24 The etiology of congenital diaphragmatic hernia: the retinoid hypothesis 20 years later | Pediatric Research

  https://www.nature.com/articles/s41390-023-02905-7

  The Retinoid Hypothesis is centered on the importance of the signaling molecule retinoic acid (RA) as a potent regulator of mammalian development. […] The formulation of the Retinoid Hypothesis had a significant impact on the field and its direction of research. […] The Retinoid Hypothesis was based on research dating back to the 1940s, drawing together several threads of evidence to justify the notion that altered retinoid signaling may cause CDH. […] The balance of this evidence led the authors to conclude that altered retinoid signaling may be a contributing factor in the etiology of CDH. […] The strongest evidence linking RA signaling and CDH in humans exists for STRA6, RALDH2, and RARB. […] Mutations in this gene cause a variety of different phenotypes, including tetralogy of Fallot, absent thymus, kidney defects, as well as diaphragm eventration/Bochdalek CDH.

• #25 The etiology of congenital diaphragmatic hernia: the retinoid hypothesis 20 years later | Pediatric Research

  https://www.nature.com/articles/s41390-023-02905-7

  The presence of diaphragm defects in Wt1, Coup-tf2, Gata4, and Fog2 mutant mice indicates their individual importance in normal diaphragm development. […] As we learn increasingly more about the genetics of CDH, a common pathway that has emerged is RA signaling, providing support for the Retinoid Hypothesis in human CDH. […] Population-based studies have provided insight into the link between CDH and the Retinoid Hypothesis, primarily in the context of adequate maternal dietary vitamin A intake. […] There is collective epidemiological evidence that low maternal dietary vitamin A intake is a risk factor for CDH, although this concept requires further exploration. […] While there is evidence to suggest that maternal dietary vitamin A intake is an important factor in the etiology of CDH, it has been observed that there is no evidence to suggest an increased incidence of CDH in countries with high rates of vitamin A deficiency.

• #26 The etiology of congenital diaphragmatic hernia: the retinoid hypothesis 20 years later | Pediatric Research

  https://www.nature.com/articles/s41390-023-02905-7

  The presence of diaphragm defects in Wt1, Coup-tf2, Gata4, and Fog2 mutant mice indicates their individual importance in normal diaphragm development. […] As we learn increasingly more about the genetics of CDH, a common pathway that has emerged is RA signaling, providing support for the Retinoid Hypothesis in human CDH. […] Population-based studies have provided insight into the link between CDH and the Retinoid Hypothesis, primarily in the context of adequate maternal dietary vitamin A intake. […] There is collective epidemiological evidence that low maternal dietary vitamin A intake is a risk factor for CDH, although this concept requires further exploration. […] While there is evidence to suggest that maternal dietary vitamin A intake is an important factor in the etiology of CDH, it has been observed that there is no evidence to suggest an increased incidence of CDH in countries with high rates of vitamin A deficiency.

• #27 The etiology of congenital diaphragmatic hernia: the retinoid hypothesis 20 years later | Pediatric Research

  https://www.nature.com/articles/s41390-023-02905-7

  Congenital diaphragmatic hernia (CDH) is a severe birth defect and a major cause of neonatal respiratory distress. […] Despite the significant impact of CDH, its etiology remains incompletely understood. […] The etiology of CDH is complex and remains largely unknown. […] It is generally considered that the two main factors that contribute to CDH are genetic and/or environmental. […] Approximately 30-40% of CDH cases have an identifiable genetic cause. […] Of this number, chromosomal defects account for about ~10% of CDH cases, and de novo mutations account for 10-22% of cases. […] Environmental risk factors for CDH are varied, including associations with maternal age, alcohol use, and smoking. […] One of the leading hypotheses to explain the etiology of CDH is the so-called Retinoid Hypothesis.

• #28 Diaphragmatic Hernias: Practice Essentials, Anatomy, Pathophysiology

  https://emedicine.medscape.com/article/934824-overview

  The etiology of CDH is largely unknown but is probably multifactorial. However, there are several reported maternal risk factors for CDH have been reported, including the following: Advanced age, Gestational diabetes, Gestational hypertension, Low body mass index (BMI), Tobacco use, Alcohol use. […] Multiple studies are currently investigating genetic factors leading to CDH; there is a known association between CDH and certain chromosomal abnormalities. An estimated 60% of CDH cases are isolated (ie, occur in healthy term pregnancies), whereas 40% are nonisolated (ie, occur in infants with an associated chromosomal or other structural anomaly). […] Abnormalities in the retinoid signaling pathway have been hypothesized to contribute to the etiology. […] The earliest link was observed when 25-40% of the offspring of rat dams fed a vitamin A-deficient diet developed CDH, and the proportion of affected pups decreased when vitamin A was reintroduced into the diet in midgestation. […] To achieve a better understanding of the underlying etiology of CDH, further research will be required.

• #29 Congenital Diaphragmatic Hernia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK556076/

  The etiology of congenital diaphragmatic hernia remains unclear. It is thought to be multifactorial with genetic, environmental, and/or nutritional factors playing a role. CDH can be an isolated anomaly or associated with anomalies in other organ systems. Multiple chromosomal aberrations (deletions, aneuploidies, etc.) and single-gene mutations (GATA4, LRP2, etc.) are associated with CDH. The most frequent aneuploidies associated with CDH include trisomy 18, trisomy 13, trisomy 21, and less frequently Turner syndrome (45, X). Some of the syndromes associated with CDH include Pallister-Killian syndrome, 8p23.1 deletion syndrome, Fryns syndrome, Cornelia de Lange syndrome. Exposure to teratogenic agents like mycophenolate mofetil, allopurinol, and lithium during pregnancy is reported to be associated with CDH. […] Recently, studies indicate disturbances in the retinoid-signaling pathway as a potential cause of CDH.

• #30 Congenital Diaphragmatic Hernia | CDH Hospital | CHOC

  https://choc.org/programs-services/pediatric-general-surgery/diaphragmatic-hernia/

  A congenital diaphragmatic hernia (CDH) is a hole in the diaphragm that occurs during fetal development. The diaphragm is the muscle that separates the chest from the abdomen. When a hole in the diaphragm occurs, it allows abdominal organs to pass through (herniate) into the chest cavity during fetal development hindering organ growth. CDH is a life-threatening condition affecting one in every 2,500-4,000 births. The most serious complication of CDH is inadequate lung development. […] There is no known cause for the development of congenital diaphragmatic hernias. There is nothing someone can do to cause or prevent their baby from developing a congenital diaphragmatic hernia.

• #31 Congenital Diaphragmatic Hernia | Children’s Wisconsin

  https://childrenswi.org/medical-care/fetal-concerns-center/conditions/infant-complications/congenital-diaphragmatic-hernia

  Congenital diaphragmatic hernia may be associated with other birth defects. As many as 50 percent of newborns who have CDH will have an associated anomaly of the central nervous system, cardiovascular, skeletal, gastrointestinal or genitourinary system. […] We do not know what causes diaphragmatic hernia. We do know it is not related to anything the mother ate or did during pregnancy.

• #32 Diaphragmatic Hernias: Practice Essentials, Anatomy, Pathophysiology

  https://emedicine.medscape.com/article/934824-overview

  CDH is often diagnosed on 20-week screening antenatal ultrasonography (US). […] Bochdalek hernias are thought to be caused by an embryologic failure in the fusion of the pleuroperitoneal folds and the transverse septum with the intercostal muscles. Morgagni hernias, on the other hand, are believed to be caused by a defect in the union of the transverse septum and lateral body wall. […] Most authors have postulated that CDH develops from failure of diaphragm muscularization prior to closure of the pleuroperitoneal canals, resulting in diaphragmatic weakness prone to herniation. Others have suggested that abnormal lung development results in a weakened mesenchymal plate with impaired diaphragm fusion. Disruptions or mutations in myofibroblasts derived from pleuroperitoneal folds may also play a role, ultimately causing abnormal diaphragm development.

• #33 Congenital Diaphragmatic hernia – a review | Maternal Health, Neonatology and Perinatology | Full Text

  https://mhnpjournal.biomedcentral.com/articles/10.1186/s40748-017-0045-1

  The etiology of CDH largely remains unclear and currently is thought to be multifactorial. The majority of the cases have an isolated diaphragmatic defect presenting with pulmonary hypoplasia and persistent pulmonary hypertension of newborn (PPHN). CDH can be associated with cardiac, gastrointestinal, genitourinary anomalies or with chromosomal aneuploidy such as trisomies. Multiple genetic factors along with environmental exposures and nutritional deficiencies have been proposed to be the possible etiologies for CDH. […] Studies in rodent models have pointed towards a disturbance in Vitamin A pathway. Nitrofen, a herbicide, when administered to pregnant rodents, results in CDH in the majority of offspring. […] The embryologic basis of CDH remains controversial. It was thought initially that the defect happened secondary to failure of different parts of the diaphragm to fuse resulting in a patent pleuroperitoneal canal. […] Another speculation is that lung hypoplasia may be the primary causal factor in the pathophysiology of diaphragmatic hernia. […] Thus the major underlying pathophysiology of CDH appears to be a combination of lung immaturity and hypoplasia that leads to PPHN.

• #34 Diaphragmatic Hernias: Practice Essentials, Anatomy, Pathophysiology

  https://emedicine.medscape.com/article/934824-overview

  CDH is often diagnosed on 20-week screening antenatal ultrasonography (US). […] Bochdalek hernias are thought to be caused by an embryologic failure in the fusion of the pleuroperitoneal folds and the transverse septum with the intercostal muscles. Morgagni hernias, on the other hand, are believed to be caused by a defect in the union of the transverse septum and lateral body wall. […] Most authors have postulated that CDH develops from failure of diaphragm muscularization prior to closure of the pleuroperitoneal canals, resulting in diaphragmatic weakness prone to herniation. Others have suggested that abnormal lung development results in a weakened mesenchymal plate with impaired diaphragm fusion. Disruptions or mutations in myofibroblasts derived from pleuroperitoneal folds may also play a role, ultimately causing abnormal diaphragm development.

• #35 Congenital Diaphragmatic hernia – a review | Maternal Health, Neonatology and Perinatology | Full Text

  https://mhnpjournal.biomedcentral.com/articles/10.1186/s40748-017-0045-1

  The etiology of CDH largely remains unclear and currently is thought to be multifactorial. The majority of the cases have an isolated diaphragmatic defect presenting with pulmonary hypoplasia and persistent pulmonary hypertension of newborn (PPHN). CDH can be associated with cardiac, gastrointestinal, genitourinary anomalies or with chromosomal aneuploidy such as trisomies. Multiple genetic factors along with environmental exposures and nutritional deficiencies have been proposed to be the possible etiologies for CDH. […] Studies in rodent models have pointed towards a disturbance in Vitamin A pathway. Nitrofen, a herbicide, when administered to pregnant rodents, results in CDH in the majority of offspring. […] The embryologic basis of CDH remains controversial. It was thought initially that the defect happened secondary to failure of different parts of the diaphragm to fuse resulting in a patent pleuroperitoneal canal. […] Another speculation is that lung hypoplasia may be the primary causal factor in the pathophysiology of diaphragmatic hernia. […] Thus the major underlying pathophysiology of CDH appears to be a combination of lung immaturity and hypoplasia that leads to PPHN.

• #36 Congenital Diaphragmatic Hernia | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-7-1

  A „dual hit” pathogenesis, in which abnormal development followed by compression cause lung hypoplasia is widely accepted. […] Pharmacologic or teratogenic models of CDH have been crucial for unveiling some pathogenic mechanisms. […] Although the mechanism by which CDH is induced in these models is not well known, disturbances of the retinoid signalling pathway, a key regulator of embryonic morphogenesis, are likely. […] Another factor that might contribute to lung hypoplasia in CDH is decreased airway pressure during fetal life.

• #37 Diaphragmatic Hernias: Practice Essentials, Anatomy, Pathophysiology

  https://emedicine.medscape.com/article/934824-overview

  CDH is often diagnosed on 20-week screening antenatal ultrasonography (US). […] Bochdalek hernias are thought to be caused by an embryologic failure in the fusion of the pleuroperitoneal folds and the transverse septum with the intercostal muscles. Morgagni hernias, on the other hand, are believed to be caused by a defect in the union of the transverse septum and lateral body wall. […] Most authors have postulated that CDH develops from failure of diaphragm muscularization prior to closure of the pleuroperitoneal canals, resulting in diaphragmatic weakness prone to herniation. Others have suggested that abnormal lung development results in a weakened mesenchymal plate with impaired diaphragm fusion. Disruptions or mutations in myofibroblasts derived from pleuroperitoneal folds may also play a role, ultimately causing abnormal diaphragm development.

• #38 Congenital Diaphragmatic Hernia (CDH) | Children’s Hospital Colorado

  https://www.childrenscolorado.org/conditions-and-advice/conditions-and-symptoms/conditions/congenital-diaphragmatic-hernia-cdh/

  A congenital diaphragmatic hernia (CDH) occurs when a baby’s diaphragm doesn’t form completely during fetal development. This leaves an opening between the chest and abdominal cavities, allowing abdominal organs to herniate (protrude or enter) into the chest cavity and prevent lung development. […] A diaphragmatic hernia usually develops about 9 to 10 weeks into pregnancy but might occur as early as 5 to 6 weeks. There is no known way to prevent CDH, and there is nothing the mother did or does that could cause their unborn baby to develop CDH. […] CDH may occur by itself (known as isolated CDH) or with other conditions. In about 10% to 20% of cases, CDH is caused by or associated with a genetic disorder, such as Down syndrome (trisomy 21), Edward’s syndrome (trisomy 18) or Patau syndrome (trisomy 13). About 60% of the time, CDH occurs with another congenital condition that affects organ structure and 40% of the time those are congenital heart defects.

• #39 Congenital diaphragmatic hernia: Prenatal issues – UpToDate

  https://www.uptodate.com/contents/congenital-diaphragmatic-hernia-prenatal-issues

  Congenital diaphragmatic hernia (CDH) is a developmental discontinuity of the diaphragm that allows the abdominal viscera to herniate into the chest. Although the diaphragmatic defect is surgically correctable, in utero herniation of viscera can result in pulmonary hypoplasia and pulmonary hypertension. A substantial percentage of CDH cases are associated with additional abnormalities, including major structural anomalies in other organ systems, chromosomal abnormalities, and/or single gene disorders. […] Failure of normal closure of the pleuroperitoneal folds during the fourth to tenth weeks postfertilization allows herniation of viscera into the thoracic cavity, which interferes with normal lung development and has several potential adverse consequences, including […] Reduction in bronchiolar branching. […] Truncation and over-muscularization of the pulmonary arterial tree, leading to smaller cross-sectional area of pulmonary vessels, structural vascular remodeling, and vasoconstriction with altered vasoreactivity.

• #40 New insights into little known but common birth defect: Congenital diaphragmatic hernia | ScienceDaily

  https://www.sciencedaily.com/releases/2015/03/150325151731.htm

  This suggested that genetic defects within connective tissue might be a cause of CDH. […] In every case in which the Gata4 gene was „knocked out,” the mouse developed a hernia in its diaphragm. […] Without Gata4 in the connective tissue, muscle develops incompletely – creating a localized region made entirely of connective tissue. […] Their genetic studies, aided by computer models made in collaboration with bioengineers, show that CDH only develops when a weaker region of connective tissue is surrounded by stronger muscular tissue; counterintuitively, diaphragms made entirely of connective tissue did not develop hernias.

• #41 New insights into little known but common birth defect: Congenital diaphragmatic hernia | ScienceDaily

  https://www.sciencedaily.com/releases/2015/03/150325151731.htm

  This suggested that genetic defects within connective tissue might be a cause of CDH. […] In every case in which the Gata4 gene was „knocked out,” the mouse developed a hernia in its diaphragm. […] Without Gata4 in the connective tissue, muscle develops incompletely – creating a localized region made entirely of connective tissue. […] Their genetic studies, aided by computer models made in collaboration with bioengineers, show that CDH only develops when a weaker region of connective tissue is surrounded by stronger muscular tissue; counterintuitively, diaphragms made entirely of connective tissue did not develop hernias.

• #42 The Genomics of Congenital Diaphragmatic Hernia | Children’s Hospital of Philadelphia

  https://www.chop.edu/news/genomics-congenital-diaphragmatic-hernia

  Congenital diaphragmatic hernia (CDH) occurs in about 1 in roughly 2,500 live births. […] While the cause of CDH is still largely unknown, there is a strong genetic contribution. CDH can recur within families and/or occur as part of genetic syndromes or chromosomal disorders. […] Genetic differences including chromosomal anomalies, copy number variants and sequence variants are identified in ~30% of patients with CDH. […] However, despite dramatic advances in genetic diagnostic capabilities, a genetic etiology is not found in approximately 70% of individuals with CDH, including most with isolated CDH. […] It is more likely that genetic contributors to isolated CDH lie in regulatory elements, microRNAs, or other elements that control gene expression in the developing diaphragm. […] At CHOP, Ian Krantz, MD, Director of the Roberts Individualized Medical Genetics Center (RIMGC) and Director of the Center for Cornelia de Lange Syndrome (CdLS) and Related Diagnoses, and his lab have characterized the molecular etiologies of two of the most common forms of syndromic CDH: CdLS and Pallister-Killian syndrome (PKS). […] Using grant funding provided by the Fore Hadley Foundation, the RIMGC, in collaboration with the CDH program at the Center for Fetal Diagnosis and Treatment (CFDT), is trying to define the underlying genetic etiologies of CDH to better understand why CDH occurs.

• #43 The Genomics of Congenital Diaphragmatic Hernia | Children’s Hospital of Philadelphia

  https://www.chop.edu/news/genomics-congenital-diaphragmatic-hernia

  Congenital diaphragmatic hernia (CDH) occurs in about 1 in roughly 2,500 live births. […] While the cause of CDH is still largely unknown, there is a strong genetic contribution. CDH can recur within families and/or occur as part of genetic syndromes or chromosomal disorders. […] Genetic differences including chromosomal anomalies, copy number variants and sequence variants are identified in ~30% of patients with CDH. […] However, despite dramatic advances in genetic diagnostic capabilities, a genetic etiology is not found in approximately 70% of individuals with CDH, including most with isolated CDH. […] It is more likely that genetic contributors to isolated CDH lie in regulatory elements, microRNAs, or other elements that control gene expression in the developing diaphragm. […] At CHOP, Ian Krantz, MD, Director of the Roberts Individualized Medical Genetics Center (RIMGC) and Director of the Center for Cornelia de Lange Syndrome (CdLS) and Related Diagnoses, and his lab have characterized the molecular etiologies of two of the most common forms of syndromic CDH: CdLS and Pallister-Killian syndrome (PKS). […] Using grant funding provided by the Fore Hadley Foundation, the RIMGC, in collaboration with the CDH program at the Center for Fetal Diagnosis and Treatment (CFDT), is trying to define the underlying genetic etiologies of CDH to better understand why CDH occurs.

• #44 The Genomics of Congenital Diaphragmatic Hernia | Children’s Hospital of Philadelphia

  https://www.chop.edu/news/genomics-congenital-diaphragmatic-hernia

  Congenital diaphragmatic hernia (CDH) occurs in about 1 in roughly 2,500 live births. […] While the cause of CDH is still largely unknown, there is a strong genetic contribution. CDH can recur within families and/or occur as part of genetic syndromes or chromosomal disorders. […] Genetic differences including chromosomal anomalies, copy number variants and sequence variants are identified in ~30% of patients with CDH. […] However, despite dramatic advances in genetic diagnostic capabilities, a genetic etiology is not found in approximately 70% of individuals with CDH, including most with isolated CDH. […] It is more likely that genetic contributors to isolated CDH lie in regulatory elements, microRNAs, or other elements that control gene expression in the developing diaphragm. […] At CHOP, Ian Krantz, MD, Director of the Roberts Individualized Medical Genetics Center (RIMGC) and Director of the Center for Cornelia de Lange Syndrome (CdLS) and Related Diagnoses, and his lab have characterized the molecular etiologies of two of the most common forms of syndromic CDH: CdLS and Pallister-Killian syndrome (PKS). […] Using grant funding provided by the Fore Hadley Foundation, the RIMGC, in collaboration with the CDH program at the Center for Fetal Diagnosis and Treatment (CFDT), is trying to define the underlying genetic etiologies of CDH to better understand why CDH occurs.

• #45 The etiology of congenital diaphragmatic hernia: Still largely unknown? – SEARCH

  https://primo.qatar-weill.cornell.edu/discovery/fulldisplay/cdi_proquest_miscellaneous_67607878/974WCMCIQ_INST:VU1

  Abstract Congenital diaphragmatic hernia (CDH) is a severe birth defect characterized by a defect in the diaphragm associated with pulmonary hypoplasia and postnatal pulmonary hypertension. Half of the cases present with other non-pulmonary congenital anomalies (so called non-isolated CDH) and in 5–10% of cases there is a chromosomal etiology. The clinical aspects of CDH are well documented but knowledge on the etiology of CDH is largely lacking. Worldwide many researchers have focused research efforts on CDH. Their findings have led to several hypotheses proposing roles for genetic and environmental factors. […] In this review we have combined these findings with our own research on the genetics of CDH in results from recent literature and propose a theory on the etiology of CDH. […] We also propose a protocol for the CDH patient that will help clinicians and researchers to obtain maximal success out of their collaborations that will eventually lead to unravelling the etiology of this intriguing birth defect.

• #46 Diaphragmatic Hernias: Practice Essentials, Anatomy, Pathophysiology

  https://emedicine.medscape.com/article/934824-overview

  The etiology of CDH is largely unknown but is probably multifactorial. However, there are several reported maternal risk factors for CDH have been reported, including the following: Advanced age, Gestational diabetes, Gestational hypertension, Low body mass index (BMI), Tobacco use, Alcohol use. […] Multiple studies are currently investigating genetic factors leading to CDH; there is a known association between CDH and certain chromosomal abnormalities. An estimated 60% of CDH cases are isolated (ie, occur in healthy term pregnancies), whereas 40% are nonisolated (ie, occur in infants with an associated chromosomal or other structural anomaly). […] Abnormalities in the retinoid signaling pathway have been hypothesized to contribute to the etiology. […] The earliest link was observed when 25-40% of the offspring of rat dams fed a vitamin A-deficient diet developed CDH, and the proportion of affected pups decreased when vitamin A was reintroduced into the diet in midgestation. […] To achieve a better understanding of the underlying etiology of CDH, further research will be required.

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