Genomic Screening for Malignant Hyperthermia Susceptibility

Leslie G. Biesecker, M.D.; Robert T. Dirksen, Ph.D.; Thierry Girard, M.D.; Philip M. Hopkins, M.D.; Sheila Riazi, M.D.; Henry Rosenberg, M.D.; Kathryn Stowell, Ph.D.; James Weber, Ph.D.

Disclosures

Anesthesiology. 2020;133(6):1277-1282. 

In This Article

Conclusions

None of these approaches alone will accomplish our objective. Instead, we recognize that it will be essential that research, screening, education, and management are integrated into a functional whole systems–based approach to end deaths from MH. This proposal is centered on a genomics-centered approach to MH susceptibility. This is not to say that a major, disruptive advance in muscle physiologic testing could not occur that would change this assessment entirely—disruptive advances are by their nature unpredictable. We propose a model for organizing the necessary genetic and anesthetic activities needed to build an integrated system that will capture all events, maximize knowledge, and reduce death and disability from this disease. We propose a flow diagram that incorporates all of these activities and builds data and expertise into the future (Figure 1).

Figure 1.

A model for the future management of malignant hyperthermia susceptibility risk through genomic screening. The blue boxes represent the current phenotypic ascertainment approach to malignant hyperthermia susceptibility, where neither contracture tests nor DNA testing is practical, and the purple boxes represent the proposed future approach, supplementing the present approach. "Abnormal testing" means the presence of a variant that is likely to cause malignant hyperthermia susceptibility. "Not abnormal testing" is the converse of that result. Boxes with an asterisk indicate steps that contracture testing should be considered to assess malignant hyperthermia risk. Note that contracture testing may be done before DNA testing or reserved for those who show no abnormality on sequencing. The phrase "history of malignant hyperthermia" should be considered as at least a reasonably strong history and "malignant hyperthermia reaction" should be considered as at least reasonably strong evidence of a malignant hyperthermia reaction.

Population screening for genetic disease is not risk-free. There will be false-positive and false-negative results. The risk of false positives would be that individuals would be offered nontriggering agents unnecessarily. False negatives could lead to very rare occurrences of MH. There is also a risk that by reducing the incidence of MH, anesthesiologists would be become less familiar with the recognition and management of a reaction. While the United States' Genetic Information Nondiscrimination Act should be protective in most cases, it is possible that some individuals who are diagnosed by screening (true or false positive) could be, for example, denied entry to the Armed Forces.

We recognize that these goals are grand and challenging. We also recognize, and indeed hope, that others will debate and help us to refine our proposals and weigh in with different approaches that could help us work toward the goal of ending deaths from MH.

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