Background: Long-gap esophageal atresia (LGEA) may have clinical and syndromic presentations different from those of esophageal atresia (EA) that affects shorter segments of the esophagus (non-LGEA). This may suggest unique underlying developmental mechanisms.
Objectives: We sought to characterize clinical differences between LGEA and non-LGEA by carefully phenotyping a cohort of EA patients, and furthermore to assess molecular genetic findings in a subset of them.
Methods: This is a retrospective cohort study to systematically evaluate clinical and genetic findings in EA infants who presented at our institution over a period of 10 years (2005-2015).
Results: Two hundred twenty-nine EA patients were identified, 69 (30%) of whom had LGEA. Tracheoesophageal fistula was present in most non-LGEA patients (158 of 160) but in only 30% of LGEA patients. The VACTERL association was more commonly seen with non-LGEA compared to LGEA (70 vs. 25%; p < 0.001). Further, trisomy 21 was more common in LGEA than in non-LGEA. 25% of LGEA patients had an isolated EA diagnosis without other anomalies, compared to <1% for non-LGEA. Chromosomal microarray analysis showed copy number variations (CNV) in 4 of 39 non-LGEA patients and 0 of 3 LGEA patients. A review of the ClinGen database showed that none of those CNV have been previously described with EA.
Conclusions: LGEA represents a unique type of EA. Compared to non-LGEA, it is more likely to be an isolated defect and associated with trisomy 21. Further, it is less commonly seen with VACTERL anomalies. Our findings suggest the involvement of unique pathways that may be distinct from those causing non-LGEA.
© 2016 S. Karger AG, Basel.