Malignant Hyperthermia: A Silent Genetic Disorder

Malignant hyperthermia is a rare genetic disorder that affects 1 in 2,000-3,000 individuals.

Malignant hyperthermia (MH) is an uncommon, genetic pharmacogentic skeletal muscle disorder affecting about 1 in 2000 to 3000 individuals.1-3 So why even be concerned with this disorder if the incidence is rare? Well, the only way to discover a patient has malignant hyperthermia is if they’ve had genetic profiling performed ahead of time. Even with proper treatment of MH crisis, it can cause death. A patient may have the genetic trait for MH and never know due to lack of exposure to any triggering agents. Anesthetic agents such as halothane, isoflurane, and methoyflurane are known triggering agents for MH.2,4 Use of succinylcholine may also carry the risk of MH occurrence.4 A patient unknowingly susceptible to MH may undergo anesthesia numerous times with no event of MH before an episode occurs.1 MH is an autosomally dominant trait, so only 1 parent has to have the trait to transfer it to the offspring, causing susceptibility.1 MH can occur to any individual at any age. The earliest reaction confirmed by testing was in a 6-month-old child.

Patients susceptible to MH have skeletal muscle receptor abnormalities that cause accumulation of calcium when exposed to certain anesthetic trigger agents.2 Every second, the body is making adjustments to maintain homeostasis. In MH, calcium homeostasis is lost, and there’s an uncontrolled release of calcium leading to an increase in myoplasmic calcium.1 This increase in calcium causes constant muscle contraction leading to death and leakage of muscle cell contents (electrolytes and proteins). Sustained muscle contractions increase metabolism and generate excessive heat leading to vital organ dysfunction.2 Patients may suffer from rhabdomyolysis due to depletion of adenosine triphosphate from continual contractions. Rhabdomyolysis and cell death may lead to hyperkalemia, which potentially may cause cardiac arrhythmias.2,4

Early signs of MH may include hypercarbia, sinus tachycardia, and muscle rigidity.2 The type of muscle rigidity may present as masseter or generalized muscle rigidity (MMR or GMR). MMR causes the inability of a patient to open their mouth; GMR more commonly presents as one of the first few signs of MH. Later signs of MH include hyperthermia, ventricular tachycardia, myoglobinuria, and excessive bleeding.2

Pediatric patients present differently depending on the age. Study results have shown that patients younger than 18 years presented with sinus tachycardia, hypercarbia, and aggressive temperature increase compared to children aged 0 to 24 months who present with lower likelihood of muscle rigidity.2

If MH is left untreated, cell death and deviation from homeostasis may lead to cardiac arrests, kidney and liver failure, brain injury, and death. It’s important to recognize patients with a family history of MH because it’s an autosomal dominant trait that’s likely passed on from generation to generation.

Once signs and symptoms of MH are detected, it’s important to discontinue the triggering agents and optimize oxygenation. The only antidote available is dantrolene.1-3 Dantrolene interferes with calcium release, reducing concentration of calcium in the myoplasm, which decreases metabolism and contractions associated with MH.

Although MH is a very rare genetic disorder, its severity is deadly. Detection often occurs after the fact, once signs and symptoms have already started developing. Research into family history allows for awareness of susceptibility. MH can occur at any age with exposure to triggering agents. It’s important to recognize the possibilities of MH occurring and appropriate measures should be taken to prevent lifetime complications and possibly death.


1. Kim D-C. Malignant hyperthermia. Korean J Anesthesiol. 2012;63(5):391-401.

2. Litman RS, et al. Malignant hyperthermia: Clinical diagnosis and management of acute crisis. UpToDate website.

3. Malignant hyperthermia. MedlinePlus website.

4. Safe and unsafe anethetics. Malignant Hyperthermia Association of the United States website.