Alternative testing for Malignant Hyperthermia

Kathryn Stowell
Massey University, Palmerston North

The in vitro contracture test (IVCT) remains the "gold standard" for diagnostic testing for Malignant Hyperthermia (MH) despite the identification of an associated gene in 1989. With the identification of causative mutations in first the ryanodine receptor (RYR1) and then the dihydropyridine receptor gene, the implementation of genetic tests for MH was envisaged. DNAbased diagnostic testing for MH was implemented first in New Zealand in 1998 and has since been introduced in other countries. Currently, this type of testing is limited to families where a causative mutation has been identified and must be implemented subject to EMHG guidelines. Wide-spread implementation of genetic testing is currently not possible due to both the heterogeneity of the disorder and discordance between genotype and phenotype within families. Nevertheless, MH susceptible (MHS) diagnoses can be made and the introduction of genetic testing has decreased the number of IVCTs carried out in selected families. The overall goal is to characterize causative mutations in all New Zealand families susceptible to MH. Because of the size of RYR1 (the major causative locus) screening for mutations is not trivial. This approach is also confounded by the observation that between 20 and 50% of MHS individuals do not exhibit linkage to RYR1. Current methods for genetic testing and their utility will be discussed and compared to other non-invasive methods. Novel approaches for the identification of candidate genes and screening for causative mutations associated with MH will also be presented. This work is supported by a grant from the New Zealand Lottery Grants Board.

Time of Presentation
Sunday 8 May 2005 - 1330-1500