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.


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

In This Article

Develop a Robust and Practical Physiologic Diagnostic Test

Accurate phenotyping is essential in the genetic investigation of any trait. Singly, none of the clinical signs of an MH reaction is specific, but a nascent reaction can be recognized by an astute clinician, and the management imperative is to abort a reaction as soon as it is suspected. It is now rare for a reaction to reach such a fulminant stage that the diagnosis is unequivocal. Even when the proband's diagnosis could be made on the basis of their clinical reaction, clinical phenotyping for other family members is challenging. Scientific advances in the genetics of MH have substantially been founded on the use of the MH susceptibility phenotype determined using contracture testing. Indeed, the original identification of the RYR1 and CACNA1S susceptibility loci, and many other large genetic studies of MH have come from countries where contracture testing of affected families is quality-controlled and practicable.

While it might be ideal that contracture testing is universally available, there are numerous barriers to this goal that are beyond the scope of this commentary. Therefore, the development of a physiologic diagnostic confirmation test that is analytically robust, but which can use tissue that can be sampled locally (ideally less invasively) and transported to the testing center, would greatly improve accessibility to MH testing. The challenge here is daunting—although we would be eager to work toward an alternative clinical phenotyping test, there are no existing data to our knowledge that point to a ready path to such an assay.