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.

Proteases are important biomarkers for many biological processes and are popular targets for therapeutics investigations. A protease can be detected by monitoring changes in the paramagnetic chemical exchange saturation transfer (PARACEST) effect of a MRI contrast agent that serves as a substrate for the protease. To translate this type of responsive PARACEST MRI contrast agent to in vivo applications, the sensitivity, timing, specificity and validation of the response of the agent must be evaluated. This report demonstrates that PARACEST MRI contrast agents can be used to detect nanomolar concentrations of proteases, can be designed to preferentially detect the protease caspase-3 relative to caspase-8, and can be detected within the 15 min time frame of typical MRI studies. The response can be validated using an unresponsive PARACEST MRI contrast agent as a control. A survey of the MEROPS database shows that this approach may also be applied to detect other proteases, and therefore may represent a new platform technology for studies of the proteasome.

VACTERL/VATER association is typically a sporadic disorder. We present data on inheritance in 78 probands with VACTERL association, and show that 9% of probands have a primary relative with at least one component feature of VACTERL association. The prevalence of component features in first-degree relatives is significantly higher than expected in the general population, which has implications for counseling of affected families and for research into possible etiologies.