Malignant Hyperthermia (MH) is a hypermetabolic crisis consisting of elevated carbon dioxide, hyperthermia, tachycardia, acidosis, rhabdomyolysis, and hyperkalemia. MH-susceptibility is a diagnostic challenge because the clinical phenotype presents only after exposure to halogenated inhalational anesthetics or succinylcholine. The majority of patients with MH have genetic linkage to the RYR1 gene, encoding the ryanodine receptor. RYR1 mutations can also lead to various myopathies including central core disease, multiminicore disease, and centronuclear myopathy.

A 67-year-old female presented with urosepsis requiring intubation. Succinylcholine was administered at the time of intubation. Shortly afterwards, the patient developed tachycardia, increased end tidal CO₂, and hyperthermia with peak fever 107.2 ºF. She was started on dantrolene with significant improvement in her vital signs. Her neurologic exam revealed areflexia and flaccid weakness in all extremities, requiring intensive physical rehabilitation for recovery.  

Nerve conduction study (NCS) revealed severe axonal sensorimotor neuropathy with completely absent sensory responses. Muscle biopsy revealed type II fiber atrophy without central cores. Although myopathic conditions are linked to MH-susceptibility, our patient’s weakness was more likely related to criticial illness polyneuropathy (CIP). Genetic testing revealed a previously unreported variant of uncertain significance in the RYR1 gene on exon 49 with glycine replacing valine at codon 2627.

In patients with vital instability following inhalational anesthetic or succinylcholine use, suspicion for MH should remain high. Disruption at codon 2627 with leucine or methionine has previously been reported as pathogenic for MH-susceptibility. Similar mutations at the same codon as well as our patient’s clinical presentation indicate that her novel missense mutation may also be pathogenic. Associated RYR1-linked myopathic conditions should also be considered in patients with weakness and MH-susceptibility. Further studies are needed to help differentiate which genetic mutations are pathogenic.