Likelihood of meeting defined VATER/VACTERL phenotype in infants with esophageal atresia with or without tracheoesophageal fistula

Abstract

Esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) is a foregut defect that is a major component of the VATER/VACTERL association. The specific diagnostic criteria for the VATER/VACTERL association phenotype have changed over time. The current definition is presence of at least three of the following: Vertebral defects, Anal atresia, Cardiac defects, TE fistula, or Renal and Limb anomalies in the absence of a specific genetic diagnosis. Using the Texas Birth Defect Registry, 1,175 cases of EA+/−TEF (174 EA; 1,001 EA + TEF) were evaluated against strict definitions of VATER/VACTERL. Nine (5.2%) cases of EA alone and 164 (16.3%) cases of EA + TEF met criteria for a diagnosis of VATER;and 20 (11.5%) and 223 (22.2%), respectively, met criteria for VACTERL. Trisomy 21, Trisomy 18, 22q11 deletion, and CHARGE were the most common syndromic diagnoses. About 88.5% (154) cases of EA and 77.8% (778) cases of EA + TEF were likely not to meet the criteria for VACTERL. EA+/−TEF is more likely to be an isolated defect or part of a multiple malformation syndrome in a pattern other than VACTERL, than be part of the defined association. This study reinforces the need to consider broader evaluation for alternate diagnoses in the presence of these defects.

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

“…Further characterization of patients who do not fit VACTERL or a recognized syndrome may reveal distinct subgroups. As pointed out by others (Bogs et al, 2018; Guptha et al, 2019; Stoll et al, 2017), ideally a standardized method of case classification, such as that outlined by the guidelines for the National Birth Defects Prevention study (Rasmussen et al, 2003), should be used when there are multiple birth defects present; we adopted these guidelines in the belief that use of a standard classification would facilitate comparison between studies (see Section 2 and Figure 1). Following these proposed approach (Rasmussen et al, 2003), we grouped the patients into different subcategories (Figure 1), including a category rarely reported in prior TEF/EA studies, teratogenic syndrome.…”

“…We required at least three VACTERL defects to diagnose VACTERL association, which complies with other studies and common practice (de Jong et al, 2008; Guptha et al, 2019; La Placa et al, 2013; Solomon et al, 2010). However, we observed a high number of patients in this study ( N = 32, 20%) with EA/TEF and only one additional classic VACTERL defect, which were classified separately as “partial VACTERL” (Figure 1); we think it is reasonable to classify them separately from patients with more complex unrecognized associations, which were categorized as “unknown” (Figure 1, Table 6).…”

“…A minority of patients underwent molecular testing which is a limitation, however the molecular test results are discussed in a few interesting patients including a possible expansion of the phenotype for BTPF . This study also includes a significant proportion of Hispanic patients (Table 1), whereas previous large studies (Bogs et al, 2018; Brosens, Ploeg, et al, 2014; Chittmittrapap, Spitz, Kiely, & Brereton, 1989; de Jong et al, 2008) have reported findings from mostly Caucasian populations or have not reported the specific race/ethnicity frequencies (Guptha, Shumate, & Scheuerle, 2019).…”

“…The frequency of overall associated anomalies was 66% (105/157) (see Figure 1). There are large series of EA/TEF patients reporting the frequency of associated anomalies (Bogs et al, 2018; Brosens, Ploeg, et al, 2014; Chittmittrapap et al, 1989; de Jong et al, 2008; Guptha et al, 2019; Holder, Cloud, Lewis, & Pilling, 1964; Pedersen et al, 2012). Stoll et al (2017) provided an extensive literature review about the frequency of associated anomalies among the published literature.…”

“…Bogs et al (2018) studied 158 patients with TEF with VACTERL association or other patterns of malformation, excluding known genetic chromosomal or single gene disorders. Guptha et al (2019) reported the birth defects associated with EA with or without TEF in a large sample of patients meeting definition of VATER or VACTERL using the Texas Birth Defect Registry data (Guptha et al, 2019).…”