Developmental and genetic aspects of congenital diaphragmatic hernia

Abstract

Congenital diaphragmatic hernia (CDH) is a frequent occurring cause of neonatal respiratory distress and occurs 1 in every 3,000 liveborns. Ventilatory support and pharmaceutical treatment of the co-occurring lung hypoplasia and pulmonary hypertension are insufficient in, respectively, 20% of isolated cases and 60% of complex ones leading to early perinatal death. The exact cause of CDH remains to be identified in the majority of human CDH patients and prognostic factors predicting treatment refraction are largely unknown. Their identification is hampered by the multifactorial and heterogenic nature of this congenital anomaly. However, application of high-resolution molecular cytogenetic techniques to patients' DNA now enables detection of chromosomal aberrations in 30% of the patients. Furthermore, recent insights in rodent embryogenesis pointed to a specific disruption of the early mesenchymal structures in the primordial diaphragm of CDH-induced offspring. Together, these data allowed for the introduction of new hypotheses on CDH pathogenesis, although many issues remain to be resolved. In this review, we have combined these new insights and remaining questions on diaphragm pathogenesis with a concise overview of the clinical, embryological, and genetic data available.

Heparan sulfate deficiency disrupts developmental angiogenesis and causes congenital diaphragmatic hernia

“…Morgagni and central tendon hernias result from defects in anterior and central tendon, respectively. Diaphragmatic hernias can occur in isolation, but in many cases, they affect lung development and cardiac function (2). The etiology of CDH appears to be heterogeneous.…”

“…The hallmark of CDH is rupture of the diaphragm and herniation of the liver, gut, and intestine into the thoracic cavity. Based on its anatomical location, CDH is classified into Bochdalek, Morgagni, and central tendon hernias (1,2). Bochdalek hernia is most common and occurs through the Bochdalek canal or foramen in the posterior diaphragm.…”

Unique Tracheal Fluid MicroRNA Signature Predicts Response to FETO in Patients With Congenital Diaphragmatic Hernia

“…Although about 10% of CDH patients have chromosomal anomalies, a common genetic cause for CDH is unknown. 7 However, it is widely accepted that the diaphragmatic defect and pulmonary hypoplasia result from a shared developmental insult. 8,9 MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression through posttranscriptional silencing of messenger RNAs.…”

What is your diagnosis?

“…Congenital diaphragmatic hernia (CDH) has an incidence of approximately 1/3,000 live births (1, 2). The primary embryological events leading to hernia remain largely unknown (3). Identification of the causes is challenging because of its heterogeneous and multifactorial character (4).…”