Spontaneous occurrence of the disposition to malignant hyperthermia.

ONE characteristic of malignant hyperthermia (MH) is the autosomal-dominant mode of inheritance. This implies that at least one parent of an affected patient should be predisposed to MH. In this report, we describe two families in which MH susceptibility developed spontaneously through a neomutation. These families attracted attention because both parents of an MH-susceptible individual were diagnosed as MH-negative in the in vitro contracture test (IVCT). The IVCT was performed with halothane and caffeine according to the protocol of the European MH Group. This test may provide the following diagnoses: MH-susceptible (MH-positive), MH-negative, or MH-equivocal (possible MH-positive). Cluster regions of the skeletal ryanodine receptor gene (RYR1), in which MH-related mutations have been identified, were amplified by polymerase chain reaction and subsequently analyzed by the direct sequencing technique previously described. Chromosome 19 microsatellite markers were amplified by polymerase chain reaction using labeled fluorescent-tag primers (D19S228, 19S421, RYR.PCR1, D19S422, D19S223, as recommended by the European MH Group, genetic section§) and were checked by fragment gel analysis in the ABI PRISM 377 DNA sequencer (Applied Biosystems, Foster City, CA).