Spectrum of congenital anomalies among VACTERL cases: a EUROCAT population-based study

Abstract

BACKGROUND: The VACTERL association is the non-random occurrence of at least three of these congenital anomalies: vertebral, anal, cardiac, tracheo-esophageal, renal, and limb anomalies. Diagnosing VACTERL patients is difficult, as many disorders have multiple features in common with VACTERL. The aims of this study were to clearly outline component features, describe the phenotypic spectrum among the largest group of VACTERL patients thus far reported, and to identify phenotypically similar subtypes. METHODS: A case-only study was performed assessing data on 501 cases recorded with VACTERL in the JRC-EUROCAT central database (birth years: 1980-2015). We differentiated between major and minor VACTERL features and anomalies outside the VACTERL spectrum to create a clear definition of VACTERL. RESULTS: In total, 397 cases (79%) fulfilled our VACTERL diagnostic criteria. The most commonly observed major VACTERL features were anorectal malformations and esophageal atresia/tracheo-esophageal fistula (both occurring in 62% of VACTERL cases), followed by cardiac (57%), renal (51%), vertebral (33%), and limb anomalies (25%), in every possible combination. Three VACTERL subtypes were defined: STRICT-VACTERL, VACTERL-LIKE, and VACTERL-PLUS, based on severity and presence of additional congenital anomalies. CONCLUSION: The clearly defined VACTERL component features and the VACTERL subtypes introduced will improve both clinical practice and etiologic research.

Cardiac, Renal and Gastrointestinal Anomalies in a Neonate: Could this be VACTERL Association? A Case Report

“…There are varied presentation of the systemic affectation. Despite the fact that vertebral anomalies and tracheaesophageal fistula/esophageal anomalies have been shown to occur in 60-70% of affected patients [9], our patient had neither. Anal atresia which is also described as a common component of the association was not reported in our patient though he did have atretic distal bowel loops with proximal bowel gaseous distension.…”

A Genetics-First Approach Revealed Monogenic Disorders in Patients With ARM and VACTERL Anomalies

“…The recently introduced VACTERL limits were used to classify our VACTERL cases in three mutually exclusive subtypes: STRICT-VACTERL, VACTERL-LIKE, and VACTERL-PLUS (9). The STRICT-VACTERL subtype contains cases with ≥3 major VACTERL features; the VACTERL-LIKE subtype contains cases with <3 major VACTERL features, but with additional minor VACTERL features adding up to ≥3 major and minor VACTERL features combined; and the VACTERL-PLUS subtype, contains cases that fulfilled either the STRICT-VACTERL or the VACTERL-LIKE subtype criteria, but had additional major congenital anomalies outside the VACTERL spectrum (9).…”

“…The prevalence of VACTERL in Europe is 0.4 in 10,000, including live births, fetal deaths (miscarriages or stillbirths from 20 weeks of gestation), and termination of pregnancy following prenatal diagnosis of a fetal anomaly (2). Any combination of three features of VACTERL qualifies for a clinical diagnosis, resulting in large phenotypic heterogeneity among VACTERL patients (3)(4)(5)(6)(7)(8)(9). VACTERL usually occurs sporadically, but in some patients, familial occurrence of component features of VACTERL has been observed, indicating that genetic factors may play a role (10).…”

Maternal risk associated with theVACTERLassociation: A case–control study

“…The recently introduced VACTERL limits were used to discriminate between major and minor VACTERL features, and additional major and minor congenital anomalies (van de Putte et al, 2019). In addition, these guidelines were used to classify our cases in three mutually exclusive subtypes: STRICT-VACTERL, VACTERL-LIKE, and VACTERL-PLUS, and to exclude the subgroup of NO-VACTERL cases (n = 12), consisting of cases originally diagnosed with VACTERL but actually not fully complying with the diagnostic criteria (van de Putte et al, 2019). This left us with 142 true VACTERL cases.…”

“…In the majority of patients, VACTERL occurs sporadically, but an increased prevalence of component features in first-degree relatives is observed (Hilger et al, 2012;Reutter & Ludwig, 2013;Salinas-Torres, Perez-Garcia, & Perez-Garcia, 2015; Solomon, Pineda-Alvarez, Raam, & Cummings, 2010). The prevalence of VACTERL was 9 in 100,000 births in the northern Netherlands in 1981-2015(van de Putte et al, 2019. Although surgical techniques have improved over the last decades, VACTERL patients still experience problems related to their congenital anomalies, such as back pain related to vertebral anomalies or incontinence related to an anal anomaly/anorectal malformation (ARM; Raam, Pineda-Alvarez, Hadley, & Solomon, 2011;Wheeler & Weaver, 2005).…”