Molecular genetic testing for malignant hyperthermia susceptibility

• Published in: Anesthesiology (Philadelphia) 2004-05, Vol.100 (5), p.1076-1080
• Main Authors: GIRARD, Thierry, TREVES, Susan, VORONKOV, Evgueni, SIEGEMUND, Martin, URWYLER, Albert
• Format: Article
• Language: English
• Subjects: Anesthesia; Anesthesia, Conduction - methods; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Confidence Intervals; Genetic Predisposition to Disease; Humans; Malignant Hyperthermia - diagnosis; Malignant Hyperthermia - genetics; Malignant Hyperthermia - physiopathology; Medical sciences; Molecular Diagnostic Techniques - methods; Muscle Contraction - genetics; Mutation; Polymerase Chain Reaction; Restriction Mapping
• ISSN: 0003-3022; 1528-1175
• DOI: 10.1097/00000542-200405000-00008

For more than 30 yr, the in vitro contracture test (IVCT) was the only appropriate diagnostic tool for malignant hyperthermia (MH). After the introduction of molecular genetics into MH research, guidelines for molecular genetic diagnosis of MH susceptibility were published. The aim of this study was to establish applicability of the guidelines, sensitivity, and specificity of genetic testing in MH and advantages for studied patients. The IVCT was performed following the guidelines of the European MH Group. Mutation analyses were performed by amplification of genomic DNA by polymerase chain reaction and restriction enzyme digestion. Two hundred eight individuals underwent MH testing between January 2001 and April 2003. In 32 of 67 initially genetic-tested patients, the familial mutation was identified, and they were diagnosed as MH susceptible. The IVCT followed negative genetic test results in 20 patients, and all but one had negative IVCT results. Three patients were scheduled to undergo elective surgery, and IVCT and genetic testing were performed simultaneously. All three had positive IVCT results and were carriers of their familial mutation. In families with known MH mutations, there is a 50% chance of reliably confirming MH susceptibility by noninvasive testing. The authors found the negative predictive value of genetic testing to be 0.95 (95% confidence interval, 0.75-0.99), but for patient safety, they still recommend following the guidelines for genetic testing in MH and therefore performing an IVCT in case of negative genetic results.