Genomic Contributors to Esophageal Atresia and Tracheoesophageal Fistula: A 12 Year Retrospective Review.

Autor: Wild KT; Division of Neonatology, The Children's Hospital of Philadelphia, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA; Division of Human Genetics, The Children's Hospital of Philadelphia, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA; Division of Human Genetics, Roberts Individualized Medical Genetics Center, The Children's Hospital of Philadelphia, Philadelphia, PA. Electronic address: wildk@chop.edu., Conlin L; Division of Genomic Diagnostics, The Children's Hospital of Philadelphia, Philadelphia, PA., Blair J; Division of Human Genetics, Roberts Individualized Medical Genetics Center, The Children's Hospital of Philadelphia, Philadelphia, PA., Manfredi M; Division of Gastroenterology, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA., Hamilton TE; Division of Pediatric General, Thoracic, and Fetal Surgery, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA., Muir A; Division of Gastroenterology, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA., Zackai EH; Division of Human Genetics, The Children's Hospital of Philadelphia, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA., Nace G; Division of Pediatric General, Thoracic, and Fetal Surgery, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA., Partridge EA; Division of Pediatric General, Thoracic, and Fetal Surgery, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA., Devine M; Division of Neonatology, The Children's Hospital of Philadelphia, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA., Reynolds T; Division of Pediatric General, Thoracic, and Fetal Surgery, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA., Rintoul NE; Division of Neonatology, The Children's Hospital of Philadelphia, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA., Hedrick HL; Division of Pediatric General, Thoracic, and Fetal Surgery, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA., Spinner N; Division of Genomic Diagnostics, The Children's Hospital of Philadelphia, Philadelphia, PA., Krantz ID; Division of Human Genetics, The Children's Hospital of Philadelphia, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA; Division of Human Genetics, Roberts Individualized Medical Genetics Center, The Children's Hospital of Philadelphia, Philadelphia, PA.
Jazyk: angličtina
Zdroj: The Journal of pediatrics [J Pediatr] 2024 Aug; Vol. 271, pp. 114060. Date of Electronic Publication: 2024 Apr 18.
DOI: 10.1016/j.jpeds.2024.114060
Abstrakt: Objective: To evaluate genetic testing utilization and diagnostic yield in infants with esophageal atresia (EA)/tracheoesophageal fistula (TEF) over the past 12 years to inform future practices and individualize prognostication and management.
Study Design: A retrospective cohort study was performed for all infants with EA or EA/TEF hospitalized between January 2011 and January 2023 at a quaternary children's hospital. For each infant, demographic information, prenatal and postnatal history, and genetic testing were reviewed.
Results: There were 212 infants who were classified as follows: 1) complex/syndromic with EA/TEF plus an additional major anatomic anomaly (n = 114, of which 74 met VACTERL criteria); 2) isolated/nonsyndromic EA/TEF (n = 88) and 3) isolated/nonsyndromic EA (n = 10). A range of genetic tests were sent with varying diagnostic rates including karyotype analysis in 12 (all with complex/syndromic phenotypes and all positive), chromosomal microarray analysis in 189 (114 of whom were complex/syndromic with an overall diagnostic rate of 3/189), single gene testing for CHD7 in 18 (4 positive), and exome analysis in 37 complex/syndromic patients (8 positive).
Conclusions: EA/TEF with and without additional anomalies is genetically heterogeneous with a broad range of associated phenotypes. While the genetic etiology of EA/TEF with or without VACTERL remains largely unknown, genome wide testing (exome or genome) including copy number analysis is recommended over chromosomal microarray testing. We anticipate that expanded genetic/genomic testing modalities such as RNA sequencing and tissue specific molecular testing are needed in this cohort to improve our understanding of the genomic contributors to EA/TEF.
Competing Interests: Declaration of Competing Interest Children's Hospital of Philadelphia Research Foundation (GRT-00003206). The authors have indicated they have no potential conflicts of interest to disclose.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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