OA/TOF is a component of the VACTERL association, which comprises Vertebral defects, Anal atresia, Cardiac defects, Tracheo‐Esophageal fistula, Renal malformations, and Limb defects. The association was first proposed by Quan and Smith in 1972,51
initially as the acronym VATER, where the letter “R” stood for “radial dysplasia”. Subsequently, the acronym was expanded to include cardiac and renal defects.52
Both terms remain in use in the literature, illustrating the problem of defining the clinical features that comprise the association. In this review, the acronym VACTERL is used except where VATER is appropriate for historical reasons.
confirmed the non‐random occurrence of the association but did not specifically address the question of which of the more peripheral elements of the association should be included within its definition. More recent studies58
have attempted to address this issue by taking, as far as possible, an approach free of ascertainment bias. The results58
indicated a distinct group of malformations corresponding with the VACTERL association, with an “upper” group associated with heart malformations and a “lower” group associated with renal malformations. The authors acknowledged the difficulty of controlling for possible bias in the way that patients are investigated which might tend to confirm some associations (oesophageal atresia, upper costo‐vertebral defects, cardiac defects), but not others where the anatomic locations are more disparate.
There are very few published series of VACTERL patients in which the clinical phenotypes have been carefully delineated, perhaps unsurprisingly in view of the difficulties of definition, and the risk of inadvertent inclusion of cases with a syndromic diagnosis. Weaver et al59
reported a series of 46 patients.
One of the key difficulties in studies of this nature is the evolving nature of our knowledge of syndromes which may overlap with or resemble the VACTERL association. Feingold syndrome, CHARGE syndrome, 22q11 deletion syndrome, Townes‐Brocks syndrome, and Pallister‐Hall syndrome (all discussed further below) show some phenotypic overlap with the VACTERL association, and most series of patients ascertained by epidemiological means are not divided into subgroups according to confirmed or possible syndromic diagnoses.
Individuals with the VACTERL association do not typically have facial dysmorphic features, learning disability, or abnormalities of growth, including head circumference. For these individuals, sibling and offspring recurrence risks are low, and are usually quoted as being around 1%. There are very few instances of recurrence of the VACTERL association in the literature. However, two examples are Nezarati and McLeod60
and Auchterlonie and White.61
Where dysmorphic features, growth abnormalities, and/or learning disability are present, a syndromic diagnosis or chromosomal abnormality may be the underlying cause, as discussed in the following section.