Eur J Pediatr Surg 2022; 32(01): 061-066
DOI: 10.1055/s-0041-1739423
Original Article

Genetic Evidence for Congenital Vascular Disorders in Patients with VACTERL Association

1   Department of Pediatric Surgery, Dr. von Hauner Children's Hospital, Munich University Hospital, Munich, Germany
2   Department of Diagnostic and Interventional Radiology, Hospital Rechts der Isar, Technical University of Munich, Munich, Germany
,
Kristina Lisec
1   Department of Pediatric Surgery, Dr. von Hauner Children's Hospital, Munich University Hospital, Munich, Germany
,
Martina Heinrich
1   Department of Pediatric Surgery, Dr. von Hauner Children's Hospital, Munich University Hospital, Munich, Germany
,
Dietrich von Schweinitz
1   Department of Pediatric Surgery, Dr. von Hauner Children's Hospital, Munich University Hospital, Munich, Germany
,
Roland Kappler
1   Department of Pediatric Surgery, Dr. von Hauner Children's Hospital, Munich University Hospital, Munich, Germany
,
Jochen Hubertus
3   Department of Pediatric Surgery, University Hospital of the Ruhr University Bochum, Bochum, Germany
› Institutsangaben

Abstract

Introduction The VACTERL association is a rare malformation complex, showing at least three anomalies of the following organ systems: vertebra, anorectum, heart and vessels, trachea and esophagus, genitourinary tract, and limbs. In addition to a multifactorial event, congenital vascular disorders are also discussed as triggers for the VACTERL association. The aim of this study was to determine whether there is a genetic background for vascular disorders triggering VACTERL association.

Materials and Methods We performed a functional analysis on whole exome sequencing data of 21 patients with VACTERL or VACTERL-like phenotype using the online analysis tool “Database for Annotation, Visualization and Integrated Discovery (DAVID) v6.8.” The study was approved by the institutional ethics committee (approval no. 026–13). Written informed consent was obtained from all patients or their parents.

Results We identified a total of 86 genetic variants (in 75 genes) classified as damaging (including probably damaging missense, nonsense, and frameshift variants), which are associated to cardiovascular development. Each investigated patient showed at least one damaging variant in genes associated to cardiovascular development. These variants were further reduced by significance in cardiovascular development to 39 genetic variants (in 33 genes). Of note, a pair of siblings, both presenting with cardiac and renal defects, had the same damaging variant in two different genes.

Conclusion Our results indicate a genetic background for congenital vascular disorders in patients with VACTERL association. In line with the literature, our data suggest that genetic mutation led to vascular diseases, which in turn may cause malformations similar to the VACTERL association.



Publikationsverlauf

Eingereicht: 18. Juli 2021

Angenommen: 05. Oktober 2021

Publikationsdatum:
25. November 2021 (online)

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