Clinical and Molecular-Genetic Studies in Esophageal Atresia

Abstract

Esophageal atresia (EA) and trachea-esophageal fistula (TEF) [MIM 189960] are severe developmental defects that aff ect one in 3,500 newborns. Slightly more boys are aff ected than girls. In The Netherlands, approximately 70 children are born annually with this congenital malformation. It is characterized by a lack of continuity of the upper gastro-intestinal tract that is oft en accompanied with a persistent connection, or fi stula, between the trachea and the esophagus (tracheo-esophageal fi stula). Five subtypes are described by the Gross classifi cati on (Figure 1A). Subtype C, with a blind-ending proximal pouch (atresia) and a distal TEF, occurs most frequently (86%), followed by the pure proximal atresia (subtype A; 7%). As is the case with other congenital malformati ons, EA/TEF occurs more in twins than in singletons, although usually only one twin is aff ected. Once a couple has one child with EA/TEF, the risk of having a second child with this anomaly goes up to 1%. Over 50% of infants with EA have additi onal anomalies, e.g. vertebral, gastro-intesti nal, urogenital, cardiovascular, renal or limb abnormalities. EA/TEF is the result of faulty septati on of the foregut. Other congenital anomalies of foregut-derived structures, such as tracheal agenesis, are also of interest. In tracheal agenesis the trachea is fully or partially absent. It occurs in one in every 50,000 births. Like EA/TEF, tracheal agenesis may be part of a complex of malformati ons, and associati ons with notably cardiovascular anomalies have been reported.