Clinical and Genetic Characterization of Esophageal Atresia: A Contemporary Cohort Integrating Phenotyping and Genomic Testing

Autores de IIS La Fe

• Purificación Marín Reina

  Autor

• Irene Reig Talamante

  Autor

• Anna Parra Llorca

  Autor

• Carla Martín Grau

  Autor

• Ángel Zúñiga Cabrera

  Autor

• Cinta Navarro Moreno

  Autor

• Alba Gabaldon Albero

  Autor

• Carmen Orellana Alonso

  Autor

• Mónica Pilar Roselló Piera

  Autor

• Pilar Sáenz González

  Autor

• 

  Francisco Martínez Castellano

  Autor

Participantes ajenos a IIS La Fe

• Escandell, IN

Grupos

• 

  Biomedicina Molecular, Celular y Genómica

• Investigación Traslacional en Genética

• Perinatología

Abstract

Background: Esophageal atresia (EA) is a complex congenital anomaly frequently associated with additional malformations and genetic conditions. Despite advances in prenatal imaging and genomic technologies, establishing an etiologic diagnosis and performing accurate risk stratification remain challenging due to marked clinical and genetic heterogeneity. Methods: We conducted a retrospective cohort study of neonates diagnosed with EA and admitted to a level IIIc neonatal intensive care unit between 2005 and 2024. Prenatal findings, associated anomalies, genetic testing results, mortality, and neurodevelopmental outcomes beyond 12 months were analyzed. Results: A total of 105 neonates were included, of whom 10.5% were diagnosed prenatally. Isolated EA was identified in 55.2% of patients, whereas 44.8% had associated anomalies, most commonly congenital cardiac defects. Clinically relevant genetic findings were identified in 10.5% of the total cohort (23.4% of complex EA cases). These findings reflect a clinically selected subgroup and should not be interpreted as diagnostic yields applicable to unselected populations or as a comparison between testing modalities. Overall mortality was 11.4%. Lower birth weight showed the strongest association with mortality in univariable analyses; however, no independent predictors were inferred due to the limited number of events. All deceased patients had complex malformative conditions and/or extreme prematurity. Among children with follow-up beyond 12 months, 88.5% demonstrated age-appropriate neurodevelopment. Conclusions: EA is characterized by substantial etiologic and phenotypic heterogeneity. Prenatal detection remains challenging, although advances in fetal imaging may improve diagnostic accuracy. A phenotype-guided approach integrating clinical evaluation and genetic testing may support etiologic diagnosis, recurrence counseling, and follow-up planning in selected patients. However, because testing was indication-driven and evolved over time, the reported diagnostic yields should not be generalized to unselected EA populations or interpreted as comparative performance across testing modalities.

Keywords

• esophageal atresia; tracheoesophageal fistula; prenatal diagnosis; genetic testing; phenotype-guided approach; VACTERL association; neurodevelopment; mortality