Analysis of component findings in 79 patients diagnosed with VACTERL association

Abstract

VACTERL association is a relatively common condition, though the causes remain poorly understood. We present data on 79 patients diagnosed with VACTERL association and perform statistical analysis on a selected subset of 60 patients with at least three component features, and who, after review, did not meet criteria for a likely alternate diagnosis. Considered individually, no two component features are significantly associated, but several multivariate statistical techniques suggest novel patterns of the co-occurrence of component features, and latent class cluster analysis demonstrates the presence of five major subgroups of patients. These findings have implications for both our understanding of VACTERL association and for the approach to research involving this condition.

Fig. 1

Inclusion characteristics of patients in this study.

Fig. 2

Six-set Edwards-Venn diagram showing overlap of features in patients included in the full analysis. V: vertebral defects; A: anal atresia; C: cardiac malformations; TE: tracheo-esophageal fistula; R: renal abnormalities; L: Limb anomalies.

Fig. 3

A. Hierarchical cluster dendogram of component features with both AU (in red, on the left side of each pair of values) and BP (in green, on the right side of each pair of values) p-values. The vertical distance between component features indicates the likelihood that CFs will co-occur. Features that tend to co-occur are vertically closer. Only the cluster that includes vertebral defects, cardiac malformations, and renal anomalies (in the red box) tends to occur at a statistically significant level. B. Multidimensional scaling (MDS) shows results similar to the HC analysis. In this two-dimensional depiction, physical distance between CFs represents the likelihood that CFs will co-occur. Features that tend to co-occur are closer to each other. Again, vertebral defects, cardiac malformations, and renal anomalies cluster most closely together. V: vertebral defects; A: anal atresia; C: cardiac malformations; TE: tracheo-esophageal fistula; R: renal abnormalities; L: Limb anomalies.

Fig. 4

Profile plot of the clusters derived from Latent class cluster analysis (LCCA). In the plot, the X-axis represents each of the CFs of VACTERL association. The Y-axis represents the probability of having each of the CFs within each cluster. V: vertebral defects; A: anal atresia; C: cardiac malformations; TE: tracheo-esophageal fistula; R: renal abnormalities; L: Limb anomalies.