Esophageal Atresia, an Anomaly of VACTERL Association or Novel Feature of the FGF10 Gene: A Case Report

Introduction: VACTERL association (VA) is defined as the nonrandom co-occurrence of at least three of the following six features: Vertebral anomalies (V), Anal atresia (A), Cardiac defects (C), Tracheo-esophageal fistula (TE), Renal defects (R), and Limb anomalies (L). The genetic basis of VA remain...

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Bibliographic Details
Authors: Escalante-Reyes, M, García-Payá, E, Re, VA, Sirera, PS, de Miguel, MN, Martínez, RS
Format: article
Status:Published version
Publication Date:2025
Country:España
Institution:Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)
Repository:r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
OAI Identifier:oai:dnet:isabial_____::55a6f30747e9604e54d3d6ce194e5d62
Online Access:https://isabial.portalinvestigacion.com/publicaciones12473
https://karger.com/msy/article-abstract/doi/10.1159/000549201/938065/Esophageal-Atresia-an-Anomaly-of-VACTERL?redirectedFrom=fulltext
Access Level:Open access
Keyword:FGF10 gene
VACTERL association
Pulmonary hypoplasia
LADD3 syndrome
Aplasia of lacrimal
Description
Summary:Introduction: VACTERL association (VA) is defined as the nonrandom co-occurrence of at least three of the following six features: Vertebral anomalies (V), Anal atresia (A), Cardiac defects (C), Tracheo-esophageal fistula (TE), Renal defects (R), and Limb anomalies (L). The genetic basis of VA remains undiscovered. Case Presentation: In this study, we report a 22-year-old male patient suspected of VA at birth (TE: esophageal atresia (EA), C: dextrocardia, without heterotaxy, and L: hypoplasia of thumb phalanges). Additionally, the patient presented lacrimal gland aplasia, xerostomia, and pulmonary hypoplasia (PH). Whole exome sequencing identified a novel loss-of-function FGF10 variant: c.2T>C; p.(Met1Thr). Pathogenic variants in the FGF10 gene are known causes of lacrimo-auriculo-dento-digital syndrome 3 or aplasia of lacrimal and salivary glands, but their association has been scarcely described in the literature. This FGF10 variant was also detected in other family members exhibiting a wide range of clinical variability; however, PH and EA were observed only in our index case. Conclusion: This report supports the involvement of the FGF10 gene in EA and PH, and expands the phenotypic spectrum of pathogenic FGF10 variants. We hypothesize that while FGF10 contributes to the development of PH or VACTERL association (VA), a yet unidentified second hit is likely necessary.