Table 4.

Individuals with Two Genetic Variants

RYR1	RYR1	CACNA1 S	CHCT (g)		Clinical History
Amino Acid Substitution			Caffeine 2mM	Halothane 3%
Arg2248Gln	Ile2358Leu	—	0.3	2.3	MH episode CGS 15
Glu3583Gln	Val4849Ile	—	1.0	2.6	MH episode CGS 18, sibling was reported to have died of MH
Arg614Cys	Thr3711Arg	—	na	na	MH episode, no details available muscle cramps & rhabdomyolysis after exercise sibling had positive CHCT
Arg3283Gln	—	Val875Met	na	na	MH death, CGS 76
Val518Ala	Tyr3933Cys	—	1.0	1.3	possible MH episode with postop rhabdomyolysis CGS 5 *
Arg1043Cys	Arg2336His	—	3.3	5.7	MH episode CGS 18, FH possible MH death, sibling had positive CHCT

Of 120 subjects, 4 were found to have 2 variants in RYR1 that could be associated with MH and one had a variant in both RYR1 and CACNA1S. The compound heterozygote with R614C and T3711R was found in a subject, who after study entry was found to be related to the subject with only the novel T3711R finding. Therefore this compound heterozygote was not included in the count of total cases in Tables 1 or 2, but it was included here.

^*Indicates the subject described in McKenney KA, Holman SJ. Delayed postoperative rhabdomyolysis in a patient subsequently diagnosed as malignant hyperthermia susceptible. Anesthesiology 2002; 96:764–5. For more clinical details see Web Supplement.

CHCT = caffeine-halothane contracture test; na = not available; MH = malignant hyperthermia; CGS = Clinical Grading Scale; FH = Family History.