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Transuterine Fetal Tracheal Occlusion Model in Mice
Published on: February 5, 2021
Association of congenital diaphragmatic hernia with limb-reduction defects
Marieke F van Dooren1, Alice S Brooks, Dick Tibboel
1Department of Pediatric Surgery, Erasmus Medical Center Sophia, Rotterdam, The Netherlands.
Insights
Congenital diaphragmatic hernia (CDH) frequently co-occurs with limb-reduction defects (LRDs), suggesting an early developmental insult affecting both. Further research into candidate genes may clarify this association in humans.
Area of Science:
- Developmental biology
- Birth defects research
- Human embryogenesis
Background:
- Congenital diaphragmatic hernia (CDH) pathogenesis is poorly understood, with potential genetic and environmental factors.
- CDH often presents with co-occurring malformations, particularly limb defects, offering insights into developmental timing.
- Investigating the co-occurrence of CDH and limb-reduction defects (LRDs) can illuminate the origins of these conditions.
Purpose of the Study:
- To examine the association between congenital diaphragmatic hernia (CDH) and limb-reduction defects (LRDs).
- To determine the frequency and characteristics of LRDs in infants with CDH.
- To explore the potential early embryological origins of co-occurring CDH and LRDs.
Main Methods:
- Descriptive study analyzing medical records of infants with posterolateral CDH and associated LRDs.
- Data collected from 146 patients at Sophia Children's Hospital and 810 infants/36 stillbirths from the California Birth Defects Monitoring Program (CBDMP).
Main Results:
- 10% of hospital CDH patients had limb defects, with about one-third being LRDs (often non-severe).
- 18.5% of registry CDH cases had limb defects, with 18 severe LRDs (primarily upper extremities).
- All CDH-LRD cases in both groups exhibited additional congenital anomalies.
Conclusions:
- LRDs in CDH cases were frequently bilateral or ipsilateral and preaxial, indicating an early embryological insult.
- Findings support a developmental link between CDH and LRDs, consistent with observations in animal models.
- Future genetic analyses of CDH-LRD patients are recommended to elucidate this human developmental association.
Background:
The pathogenesis of congenital diaphragmatic hernia (CDH), a severe birth defect, is not well understood; however, both developmental genes and environmental factors have been suggested to be involved. CDH is frequently associated with malformations of other structures, such as limbs, whose embryogenesis is better understood. An examination of the co-occurrence of developmental defects may provide clues as to the origin and timing of the insult to the diaphragm and limbs. Our focus was on CDH-associated limb-reduction defects (LRDs).
Methods:
For this descriptive study, we reviewed the medical records of infants with a posterolateral (Bochdalek) CDH and an associated LRD among 146 patients from the Sophia Children's Hospital, and among 810 infants and 36 stillbirths from the California Birth Defects Monitoring Program (CBDMP).
Results:
In the hospital group, 14 patients (10%) had an associated limb defect, of which about one-third were LRDs (of these, most were of a nonsevere type, such as hypoplasia of fingers). In the registry group, a limb defect was found in 162 cases (18.5%), 18 of which were mostly severe LRD (usually of the upper extremities). Additional congenital anomalies were observed in all CDH-LRD cases in both groups.
Conclusions:
In the registry group, 77.8% of LRDs were either bilateral or ipsilateral, and were mostly preaxial, suggesting an early embryological insult affecting both precursor anlages. These results, from large numbers of cases, support the notion of a developmental association between CDH and LRD, as has been observed in several knockout mice. Future analyses of candidate genes from patients with CDH and LRD may elucidate this developmental association in humans.
