Clinical geneticists' views of VACTERL/VATER association

Abstract

VACTERL association (sometimes termed "VATER association" depending on which component features are included) is typically defined by the presence of at least three of the following congenital malformations, which tend to statistically co-occur in affected individuals: Vertebral anomalies, Anal atresia, Cardiac malformations, Tracheo-Esophageal fistula, Renal anomalies, and Limb abnormalities. Although the clinical criteria for VACTERL association may appear to be straightforward, there is wide variability in the way clinical geneticists define the disorder and the genetic testing strategy they use when confronted with an affected patient. In order to describe this variability and determine the most commonly used definitions and testing modalities, we present the results of survey responses by 121 clinical geneticists. We discuss the results of the survey responses, provide a literature review and commentary from a group of physicians who are currently involved in clinical and laboratory-based research on VACTERL association, and offer an algorithm for genetic testing in patients with this association.

Figure 1

Suggested algorithm for the molecular work-up of patients with features of VACTERL association seen in the postnatal setting (see also Table V). The first step involves thorough medical and family history and a detailed physical examination, as well as imaging studies, in order to determine the presence and type of congenital malformations. Clinicians must keep in mind the differential diagnosis, especially those conditions for which testing is available. If there is no evidence for a specific overlapping condition (see Table V for a list of conditions and features), and the features of VACTERL association are classic, the two tests that might be performed for all patients are a microarray and Fanconi anemia testing (to be clear, ruling-out cytogenetic disorders and Fanconi anemia might also be better considered to be part of a thorough differential-diagnosis related work-up). A positive result would lead to familial testing, counseling, and further referrals as necessary. In the instance of a negative test, referral to an appropriate research center for discussion of further research-based testing may be considered.