Am J Med Genet A

. 2022 Oct 21.

 doi: 10.1002/ajmg.a.62989. Online ahead of print. https://pubmed.ncbi.nlm.nih.gov/36271508/

Retrospective evaluation of clinical and molecular data of 148 cases of esophageal atresia

Emmanuelle Ranza ^1 2 3, Morgane Le Gouez ⁴, Anne Guimier ^1 5, Naziha Khen Dunlop ⁶, Sylvie Beaudoin ⁶, Valérie Malan ¹, Caroline Michot ¹, Geneviève Baujat ¹, Marlène Rio ¹, Valérie Cormier-Daire ^1 5, Véronique Abadie ⁴, Sabine Sarnacki ⁶, Christophe Delacourt ⁷, Stanislas Lyonnet ^1 5, Tania Attié-Bitach ^1 5, Véronique Pingault ^1 5, Véronique Rousseau ⁶, Jeanne Amiel ^1 5

Affiliations expand

• PMID: 36271508
• DOI: 10.1002/ajmg.a.62989

Abstract

Developmental abnormalities provide a unique opportunity to seek for the molecular mechanisms underlying human organogenesis. Esophageal development remains incompletely understood and elucidating causes for esophageal atresia (EA) in humans would contribute to achieve a better comprehension. Prenatal detection, syndromic classification, molecular diagnosis, and prognostic factors in EA are challenging. Some syndromes have been described to frequently include EA, such as CHARGE, EFTUD2-mandibulofacial dysostosis, Feingold syndrome, trisomy 18, and Fanconi anemia. However, no molecular diagnosis is made in most cases, including frequent associations, such as Vertebral-Anal-Cardiac-Tracheo-Esophageal-Renal-Limb defects (VACTERL). This study evaluates the clinical and genetic test results of 139 neonates and 9 fetuses followed-up at the Necker-Enfants Malades Hospital over a 10-years period. Overall, 52 cases were isolated EA (35%), and 96 were associated with other anomalies (65%). The latter group is divided into three subgroups: EA with a known genomic cause (9/148, 6%); EA with Vertebral-Anal-Cardiac-Tracheo-Esophageal-Renal-Limb defects (VACTERL) or VACTERL/Oculo-Auriculo-Vertebral Dysplasia (VACTERL/OAV) (22/148, 14%); EA with associated malformations including congenital heart defects, duodenal atresia, and diaphragmatic hernia without known associations or syndromes yet described (65/148, 44%). Altogether, the molecular diagnostic rate remains very low and may underlie frequent non-Mendelian genetic models.

Keywords: VACTERL; associated anomalies; esophageal atresia; genetics of esophageal atresia.

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