Genetic Testing in a Cohort of Complex Esophageal Atresia

Abstract

The objective of the present study is to describe a cohort of complex esophageal atresia and the yield of genetic tests performed for such patients. We selected 45 patients with complex esophageal atresia (EA), namely those having at least one associated anomaly. We reviewed their medical records to assess clinical features, other diagnoses, and genetic investigations. Most of the patients had a diagnosis of VACTERL association (56%) with no genetic variant identified. Interestingly, 5 patients in the cohort (11%) had a right pulmonary hypoplasia or agenesis. A majority of our cohort (73%) had genetic testing; 60% were karyotyped (abnormal in 4 of the 27 patients tested), 31% had aCGH (abnormal in 1 of the 14 patients tested), and 31% had diepoxybutane (DEB) testing for Fanconi anemia (abnormal in 2 of the 14 patients tested). One patient had exome sequencing studies, but no candidate gene was identified. Various anomalies were associated with EA, and overall a genetic variant could be identified in 7 of the 33 patients tested. Chromosomal studies such as aCGH and chromosomal breakage studies should be considered, and their yield varied between 7 and 14%. Other genetic investigations such as exome sequencing could possibly have even higher yields but will need to be assessed in a large cohort. Improved genetic diagnoses in EA may improve the management of these patients by directing specific surveillance and management schemes.

Patterns of malformation associated with esophageal atresia/tracheoesophageal fistula: A retrospective single center study

“…A limitation of this study is that only 18 patients underwent microarray testing (4/9 in the “unknown group”) and only two patients underwent whole exome sequencing (1/9 in the “unknown group”). However, this is still higher than the few studies published focusing on the molecular diagnosis of patients with EA (Beauregard‐Lacroix et al, 2017). Two patients of unknown category had VUS (Table 6).…”

The etiology of VACTERL association: Current knowledge and hypotheses

“…First, cytogenomic investigations have included studies of multiple series of patients with VACTERL and/or multiple features of the condition (Beauregard‐Lacroix et al, ; Brosens et al, ; Solomon et al, ; Zhang et al, ). While these studies reported the identification of pathogenic variants as well as alleles of interest that may act as susceptibility factors, no frequently recurring copy number variants (CNVs) or other structural variants detectable by these technologies has been identified, though some interesting suggestions have emerged, such as heterozygous deletion of chromosome 13q (Walsh, Vance, & Weaver, ).…”

Respiratory Morbidity in Children with Repaired Congenital Esophageal Atresia with or without Tracheoesophageal Fistula

“…In 36% of cases, these may occur as part of the VACTERL spectrum (vertebral anomalies, anorectal atresia, congenital heart malformations, tracheoesophageal fistula, renal abnormalities, and limb defects) or CHARGE syndrome (coloboma, heart defects, atresia choanae, retardation of growth and/or development, genital hypoplasia, and ear deformities). Trisomies of chromosomes 18 and 21, Di George syndrome and Pierre Robin syndrome are other significant risk factors for CEA ± TEF [ 7 , 8 , 9 ]. These underlying diseases may be detected before birth.…”