Results of in vitro contracture testing of both parents of malignant hyperthermia susceptible probands.

BACKGROUND

Malignant Hyperthermia (MH) is regarded as a dominantly inherited condition. Therefore, most investigators do not test the second parent if the first parent is found to be MH susceptible (MHS). The purpose of this study was to validate this policy.

METHODS

In vitro contracture tests (IVCT) have been performed in both parents of 101 MH susceptible probands. Diagnoses were made according to the European MH group protocol and include MH susceptible (MHS), MH equivocal (MHE) and MH negative (MHN). Our control material consists of 60 patients without any personal or family history of MH.

RESULTS

Thirty-seven pairs of parents were MHS-MHN, 20 were MHE-MHN, 6 were MHS-MHS, 20 were MHS-MHE, 6 were MHE-MHE, and 12 were MHN-MHN. The frequency of MHE was greater in the parents than in the controls (26% versus 8%, P < 0.05). Several possible explanations exist: the IVCT produces false positive and/or false negative results; the MH genes may be more frequent in the population than previously expected; MH susceptibility may have more than one mode of inheritance; the mutation rate may not be negligible. Our test results in controls and fulminants point at a combination of these explanations.

CONCLUSIONS

We conclude that both parents should be tested whenever possible. For genetic research it is important that labelling any parent "presumed normal" may give misleading results.