Dear Dr Weisel
We wish to thank Dr Protopapas for his thoughtful comments on our manuscript “Major adverse cardiac events in children with Williams syndrome undergoing cardiovascular surgery: An analysis of the Society of Thoracic Surgeons Congenital Heart Surgery Database.” The hypothesis brought forward that elastin pathology is at the source of the abnormal vascular development seen in some patients with Williams syndrome appears well-founded and worthy of continued study 1.
The promise of genetic information driving clinical decision making in congenital heart disease is appealing, particularly in high risk patients with variable outcomes, such as those with Williams syndrome 2. Turning this promise into reality first requires establishing strong genotype-phenotype relationships. This will best be accomplished by routinely collecting and analyzing genetic data from large patient cohorts 3. In a subsequent step, the identified genetic information will need to be linked to a clinical outcome. While the routine collection of genetic information is undoubtedly complex and requires a strong infrastructure, the overall task may be simplified by using existing clinical outcomes data sources. The Society of Thoracic Surgeons Congenital Heart Surgery Database, as the largest and most comprehensive congenital heart surgery data repository in the world, is an excellent source of such data 4.
Given the variability in clinical outcomes described in our study, and the potential genetic mechanism hypothesized by Dr Protopapas and others, Williams syndrome patients may be an ideal population in which to study prospectively genetic sample collection combined with standard of care clinical outcomes data. If successful in identifying a genotype-phenotype relationship, such a study might demonstrate the feasibility and efficiency of a novel mechanism to help advance the causation model of congenital heart disease.
Footnotes
Disclosures: Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under award number UL1TR001117 (Hornik and Hill) and by the National Heart, Lung, and Blood Institute under award number K08HL103631 (Pasquali). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, which had no role in study design; the collection, analysis, and interpretation of data; the writing of the report; or the decision to submit the manuscript for publication. The authors have no potential conflicts of interest to report.
References
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