Foregut development: an act of balance

Esophageal atresia (EA) is a relatively rare congenital anomaly in which there is no connection between the proximal esophagus and the stomach. In more than 90% of patients, the distal esophagus has an abnormal connection to the trachea; this is called a trachea-esophageal fistula (TEF). Approximately two thirds of patients also have other major malformations, mostly one or more of the types of defects included in the so-called VACTERL association: vertebral, anorectal, cardiac, tracheo-esophageal, renal or urinary tract, and limbs malformations). In the Erasmus MC-Sophia cohort of trachea-esophageal anomalies (TE) nine percent of patients have a known genetic syndrome and another 1-2% the condition is strongly associated with an environmental factor. This leaves almost 90% of TE disease burden unexplained. Using two relatively new techniques, SNP-array and whole exome sequencing we aimed to explore genetic variation in EA/TEF and VACTERL association.