J Pediatr

. 2022 Apr 14;S0022-3476(22)00326-2. doi: 10.1016/j.jpeds.2022.04.012. Online ahead of print. https://pubmed.ncbi.nlm.nih.gov/35430246/

The Genomics of Congenital Diaphragmatic Hernia: A 10 Year Retrospective Review

K Taylor Wild ¹, Erica Schindewolf ², Holly L Hedrick ³, Natalie E Rintoul ⁴, Tiffiney Hartman ⁵, Juliana Gebb ², Julie S Moldenhauer ², Elaine H Zackai ⁶, Ian D Krantz ⁵Affiliations expand

• PMID: 35430246
• DOI: 10.1016/j.jpeds.2022.04.012

Abstract

Objective(s): To evaluate genetic testing utilization in infants with congenital diaphragmatic hernia over the past decade to better inform future practices and individualize prognostication and management.

Study design: A retrospective cohort study was performed of all infants with CDH enrolled in the Pulmonary Hypoplasia Program at Children’s Hospital of Philadelphia, born between January 2011-February 2021. For each infant, demographic information, prenatal and postnatal history, and genetic testing were reviewed.

Results: Charts of 411 infants were analyzed. Overall, 22% (N=89) were complex/syndromic and 78% (N=322) were isolated/non-syndromic. Mortality was significantly higher in complex/syndromic infants (p<0.001) and in infants with diagnostic genetic testing (p <0.001). Microarray was diagnostic in 9% (N=34/399) and exome sequencing was diagnostic in 38% (N=15/39). Genetic testing was diagnostic in 57% (N=51/89) of complex/syndromic infants, but in only 2% of isolated/non-syndromic infants (N=8/322). Overall, genetic testing was diagnostic in 14% (N=56).

Conclusion(s): The high diagnostic rate in this cohort highlights the utility of comprehensive genetic testing in infants with CDH. However, 43% of complex/syndromic and 98% of isolated/non-syndromic infants do not have a genetic etiology identified. This underscores the need for additional genetic and genomic studies (e.g. whole genome, RNA sequencing) to identify novel genes and mutational mechanisms (single genes, regulatory elements, complex traits) that will allow for improved diagnostic rates and ultimately individualized management of infants with CDH.

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