Neurodevelopmental outcome in congenital diaphragmatic hernia survivors: role of ventilatory time

Congenital diaphragmatic hernia (CDH) is a severe congenital anomaly that is often accompanied by other anomalies. Although the role of genetics in the pathogenesis of CDH has been established, only a small number of disease genes have been identified. To further investigate the genetics of CDH, we analyzed de novo coding variants in 827 proband-parent trios and confirmed an overall significant enrichment of damaging de novo variants, especially in constrained genes. We identified LONP1 (Lon Peptidase 1, Mitochondrial) and ALYREF (Aly/REF Export Factor) as novel candidate CDH genes based on de novo variants at a false discovery rate below 0.05. We also performed ultra-rare variant association analyses in 748 cases and 11,220 ancestry-matched population controls and identified LONP1 as a risk gene contributing to CDH through both de novo and ultra-rare inherited largely heterozygous variants clustered in the core of the domains and segregating with CDH in familial cases. Approximately 3% of our CDH cohort was heterozygous with ultra-rare predicted damaging variants in LONP1 who have a range of clinical phenotypes including other anomalies in some individuals and higher mortality and requirement for extracorporeal membrane oxygenation. Mice with lung epithelium specific deletion of Lonp1 die immediately after birth and have reduced lung growth and branching that may at least partially explain the high mortality in humans. Our findings of both de novo and inherited rare variants in the same gene may have implications in the design and analysis for other genetic studies of congenital anomalies.

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The Role of Predictors Parameters in the Management Policy and Outcome of Congenital Diaphragmatic Hernia with the Lack of Resources in Single Pediatric Surgery Unit

International Journal of Biomedical Engineering and Clinical Science ◽

10.11648/j.ijbecs.20170306.17 ◽

2017 ◽

Vol 3 (6) ◽

pp. 110

Author(s):

Mohammed Joudi Aboud

Keyword(s):

Congenital Diaphragmatic Hernia ◽

Diaphragmatic Hernia ◽

Pediatric Surgery ◽

Management Policy

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ROLE OF DOPPLER ULTRASOUND MEASUREMENTS OF FETAL RESPIRATORY FUNCTION IN CASES OF CONGENITAL DIAPHRAGMATIC HERNIA

Journal of obstetrics and women s diseases ◽

10.17816/jowd63143-43 ◽

2014 ◽

Vol 63 (1) ◽

pp. 43-43

Author(s):

S Badalyan

Keyword(s):

Congenital Diaphragmatic Hernia ◽

Doppler Ultrasound ◽

Diaphragmatic Hernia ◽

Respiratory Function ◽

Ultrasound Measurements

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The Role of the Fetal MRI to Predict the Postnatal Survival in Fetuses with Congenital Diaphragmatic Hernia

Journal of Dr Behcet Uz Children s Hospital ◽

10.5222/buchd.2021.43925 ◽

2021 ◽

Author(s):

Fatma Ceren Sarıoğlu ◽

Orkun Sarıoğlu ◽

İnci Türkan Yılmaz ◽

Bahar Konuralp Atakul ◽

Deniz Öztekin ◽

...

Keyword(s):

Congenital Diaphragmatic Hernia ◽

Diaphragmatic Hernia ◽

Fetal Mri ◽

Lung Parenchyma ◽

P Value ◽

Total Lung Volume ◽

Ipsilateral Lung ◽

Liver Herniation ◽

Magnetic Resonance Imaging Mri

Objective: To assess the role of the magnetic resonance imaging (MRI) to predict the postnatal survival in patients with congenital diaphragmatic hernia (CDH). Method: 25 patients with CDH who had fetal MRI between 2015 and 2020 were enrolled in this retrospective study. Patients were divided into two groups according to the postnatal survival at 30 days of age: alive and dead. The fetal MRI images were assessed to calculate the lung-to-liver signal intensity ratio (LLSIR), and the total lung volume (TLV). In addition, the site of the defect (right or left), accompanying liver herniation (present or absent), detectable-ipsilateral lung parenchyma at the apex (present or absent) were also recorded. MRI images were evaluated by two pediatric radiologists. A p value lesser than 0.05 was considered statistically significant. Results: Among 25 fetuses, 6 were alive and 19 were dead within 30 days after birth. The detectable lung parenchyma had a relationship with the alive group (p = 0.023). Observed-to-expected TLV (p = 0.001) and LLSIR (p = 0.023) were significantly lower in the dead group. Using the cutoff values for the observed-to-expected TLV as 0.27 (a sensitivity of 84%, a specificity of 84%) and for the LLSIR as 2.02 (a sensitivity of 89%, a specificity of 67%) were found as predictors for death. Conclusion: The postnatal survival in CDH may be predicted using the observed-to-expected TLV and LLSIR on the fetal MRI. The presence of the detectable-ipsilateral lung parenchyma at the apex may also be associated with the postnatal survival.

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