Prospects for the diagnosis of malignant hyperthermia susceptibility using molecular genetic approaches

Abstract

MHS is a heterogeneous pharmacogenetic disorder in the human that is likely to be caused by one of a variety of genetic defects, in one of a number of genes. Direct molecular methods will provide a rapid, efficient, noninvasive, and low-cost screening test once the causative genetic mutations have been identified. However, until this objective is met, indirect molecular genetic methods can be used to demonstrate the inheritance of an abnormal gene in certain family members at risk. This requires localizing the gene that produces the abnormal phenotype to a subchromosomal segment by linkage analysis and showing the coinheritance of MHS and DNA markers in a number of family members. Indirect molecular genetic methods are likely to be particularly useful in the diagnostic evaluation of children too small to be biopsied in families where others have been biopsied or their phenotypes are known. It appears likely that molecular genetic methods will not eliminate the usefulness of the muscle biopsy and caffeine-halothane contracture test in the near future. Rather, these diagnostic tests will complement one another and significantly improve our understanding of the complexity of this disorder.