Investigation of a family following fulminant malignant hyperthermia.

UNLABELLED:Malignant hyperthermia (MH) is a pharmacogenetic neuromuscular disorder triggered by inhalational anesthetics or succinylcholine. We studied in detail 24 relatives of a patient who died after experiencing MH. All steps of the screening procedure follow developments in testing for the diagnosis of MH susceptibility from 1984 until 2002. PATIENTS AND METHODS:: The screening procedure contained a general assessment and a clinical examination; creatine kinase (CK) measurement; genomic DNA isolation for linkage analysis and mutation screening; muscle samples were tested according to the in vitro contracture test protocol (IVCT) and examined histologically; and cultured skeletal muscle cells were used to examine the effect of halothane on the intracellular calcium concentration. RESULTS:: No correlation was found between IVCT results, serum CK, or abnormal findings after histologic examination, although CK elevation and the observation of cores seemed indicative for MH susceptibility in this family. Linkage analysis implicated RYR1 on chromosome 19q13.1 as the disease susceptibility locus in the family. The calcium response was found to be significantly different. CONCLUSION:: Following 3 decades of screening for MH, the gold standard for diagnosis remains the IVCT for detection of susceptibility to MH.