Genetic diagnoses and associated anomalies in fetuses prenatally diagnosed with esophageal atresia

Abstract

Esophageal atresia (EA) is a congenital anomaly occurring in 2.3 per 10,000 live births. Due to advances in prenatal imaging, EA is more readily diagnosed, but data on the associated genetic diagnoses, other anomalies, and postnatal outcome for fetuses diagnosed prenatally with EA are scarce. We collected data from two academic medical centers (n = 61). Our data included fetuses with suspected EA on prenatal imaging that was confirmed postnatally and had at least one genetic test. In our cohort of 61 cases, 29 (49%) were born prematurely and 19% of those born alive died in the first 9 years of life. The most commonly associated birth defects were cardiac anomalies (67%) and spine anomalies (50%). A diagnosis was made in 61% of the cases; the most common diagnoses were vertebral defects, anal atresia, cardiac anomalies, tracheoesophageal fistula with esophageal atresia, radial or renal dysplasia, and limb anomalies association (43%, although 12% met only 2 of the criteria), trisomy 21 (5%), and CHARGE syndrome (5%). Our findings suggest that most fetuses with prenatally diagnosed EA have one or more additional major anomaly that warrants a more comprehensive clinical genetics evaluation. Fetuses diagnosed prenatally appear to represent a cohort with a worse outcome.

Esophageal Atresia With or Without Tracheoesophageal Fistula: Comorbidities, Genetic Evaluations, and Neonatal Outcomes

“…Of note, during the study period, there were no standards in place, either national or institutional practice guidelines, as to what medical evaluations such as echocardiography or renal ultrasound, should be performed in patients with EA/TEF or what genetic testing if any, should be undertaken. Often, patients with EA/TEF are assigned a diagnosis of VACTERL without meeting all criteria or having undergone any genetic testing as seen in our cohort and others [2]. Guptha et al described that EA/TEF is more likely to be a part of an alternate syndrome other than VACTERL using a large registry [18] and thus requires comprehensive genetic testing evaluation even when a diagnosis of VACTERL is in the differential diagnosis [2].…”

“…Often, patients with EA/TEF are assigned a diagnosis of VACTERL without meeting all criteria or having undergone any genetic testing as seen in our cohort and others [2]. Guptha et al described that EA/TEF is more likely to be a part of an alternate syndrome other than VACTERL using a large registry [18] and thus requires comprehensive genetic testing evaluation even when a diagnosis of VACTERL is in the differential diagnosis [2].…”

“…Esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) is a congenital developmental defect of the gastrointestinal tract with a prevalence of nearly 2.3 per 10,000 live births [1]. There are certain non-specific signs on prenatal ultrasound including polyhydramnios, small fetal stomach, and dilated esophageal pouch that can lead to suspicion for EA/TEF, but prenatal detection remains challenging with a low overall detection rate [2,3]. Patients identified after birth can present with copious oral secretions, gagging, and/or respiratory distress in the neonatal period [4].…”

“…There are very few retrospective studies [2,13] or case reports [14,15] describing what genetic testing is helpful in this population or the types and numbers of genetic diagnoses made from that testing. A retrospective study by Beauregard-Lacroix et al [13] in a cohort of complex EA (n= 45) looked at types of genetic testing which included chromosome analysis (73%), chromosomal microarray analysis (31%) and diepoxybutane for Fanconi anemia (31%) which yielded seven molecular diagnoses in a total of 33 patients tested.…”

“…In another cohort in France [16] of 116 patients with EA, the genetic yield was around 12%; however, the type and yield of genetic testing were not reported. A more recent study looking at genetic diagnoses in fetuses prenatally diagnosed with EA [2] had a yield of seven molecular diagnoses in a cohort of 61 patients.…”