Infantile hypertrophic pyloric stenosis in patients with esophageal atresia

Background Patients born with esophageal atresia (EA) have a higher incidence of infantile hypertrophic pyloric stenosis (IHPS), suggestive of a relationship. A shared etiology makes sense from a developmental perspective as both affected structures are foregut derived. A genetic component has been described for both conditions as single entities and EA and IHPS are variable components in several monogenetic syndromes. We hypothesized that defects disturbing foregut morphogenesis are responsible for this combination of malformations. Methods We investigated the genetic variation of 15 patients with both EA and IHPS with unaffected parents using exome sequencing and SNP array‐based genotyping, and compared the results to mouse transcriptome data of the developing foregut. Results We did not identify putatively deleterious de novo mutations or recessive variants. However, we detected rare inherited variants in EA or IHPS disease genes or in genes important in foregut morphogenesis, expressed at the proper developmental time‐points. Two pathways were significantly enriched (p