Who is most susceptible to malignant hyperthermia?

September 24, 2025 •

4 min read

Malignant hyperthermia is a rare but life-threatening inherited genetic disorder that can cause a severe reaction to certain anesthetic drugs. It is not a common condition, but understanding who is most susceptible to malignant hyperthermia is critical for both patients and healthcare providers to ensure safety during surgical procedures.

Quick Summary

The individuals most at risk for malignant hyperthermia are those with a family history of the condition, as it is an inherited autosomal dominant trait caused by specific gene mutations. Other risk factors include a personal or family history of certain muscle diseases, unexplained rhabdomyolysis, or a prior suspicious anesthetic event.

Key Points

Family History is Crucial: A history of malignant hyperthermia in a close relative is the strongest indicator of susceptibility due to the autosomal dominant inheritance pattern.
Genetic Mutations Are the Cause: The condition is caused by genetic mutations, most commonly in the RYR1 gene, affecting calcium regulation in muscle cells.
Associated Muscle Disorders Increase Risk: Certain muscle diseases, including Central Core Disease and Multiminicore Disease, are associated with a higher risk of MHS.
Anesthetic Triggers Are the Main Concern: Exposure to specific inhaled anesthetics or the muscle relaxant succinylcholine is the classic trigger for a crisis.
Non-Anesthetic Triggers Exist: In rare cases, strenuous exercise in high heat or certain viral illnesses can also trigger a hypermetabolic reaction.
Identification and Screening are Vital: Proper screening through family history review, genetic testing, or muscle biopsy is essential for identifying and protecting at-risk individuals.
Pediatric and Male Risk: Malignant hyperthermia occurs more frequently in males and in patients under 19, making these populations a focus for vigilant monitoring.

Understanding the Genetics of Malignant Hyperthermia Susceptibility (MHS)

At its core, malignant hyperthermia susceptibility (MHS) is a genetic condition. It is inherited in an autosomal dominant pattern, meaning a person needs to inherit only one copy of the altered gene from one parent to be susceptible. The most common genetic mutation associated with MHS is in the RYR1 gene, which controls a calcium release channel in skeletal muscle cells.

When a susceptible individual is exposed to triggering agents, this abnormal channel can release an excessive amount of calcium, causing a hypermetabolic state in the muscle cells. This metabolic crisis leads to symptoms such as rapid heart rate, muscle rigidity, and a dangerously high body temperature. While a family history is the strongest indicator, not everyone with the gene mutation will experience an episode upon every exposure to a trigger.

Primary Risk Groups: Family History and Genetic Predisposition

The most critical risk factor for MHS is a family history of the condition.

Direct Relatives

First-degree relatives: Children of a person with confirmed MHS have a 50% chance of inheriting the susceptibility. This also applies to parents and siblings of an affected individual.
Other relatives: The risk extends to more distant relatives, although the chance decreases. Guidance from a genetic counselor or a specialist in MH is often recommended to determine the risk for more distant family members.

Genetic Variants and Associated Conditions

Certain genetic disorders are strongly linked with MHS. Some individuals with these myopathies may be unaware of their underlying susceptibility until they are exposed to a trigger. Key conditions include:

Central Core Disease
Multiminicore Disease
King-Denborough syndrome
STAC3 Disorder

Other Predisposing Risk Factors

Beyond genetics, several other factors can increase a person's risk or indicate a potential susceptibility to malignant hyperthermia. These findings warrant careful review of the patient's history.

A history of an anesthetic event: A personal history of a prior event suspected to be malignant hyperthermia during anesthesia, even if not officially diagnosed, is a major red flag.
Unexplained rhabdomyolysis: Recurrent episodes of muscle tissue breakdown (rhabdomyolysis), particularly when triggered by strenuous exercise in extreme heat or humidity, can indicate an underlying susceptibility.
Idiopathic elevated creatine kinase (CK): Unexplained and persistently high levels of creatine kinase, an enzyme found in muscle tissue, may suggest an underlying muscle abnormality associated with MHS.
Masseter muscle rigidity (MMR): This is a rare, but significant sign, particularly in children, involving jaw muscle rigidity after administering succinylcholine.
Pediatric patients: Reactions occur more frequently in males and in patients under 19 years of age. While the reasons are not fully understood, children, especially young men, are a recognized at-risk demographic.

Comparison of Malignant Hyperthermia Triggers

The classic triggers for malignant hyperthermia are anesthetic agents used during surgery. However, non-anesthetic factors can also induce a hypermetabolic state in susceptible individuals.


Trigger Category	Anesthetic Triggers	Non-Anesthetic Triggers
Mechanism	Specific inhaled gases and succinylcholine directly activate the abnormal calcium channels in muscle cells.	Environmental heat or strenuous exercise can stress the system and induce a hypermetabolic response.
Common Examples	Halothane, Sevoflurane, Desflurane, Isoflurane, and Succinylcholine.	Intense physical activity in hot climates, high ambient temperatures, and certain viral illnesses.
Effect on Susceptible Individuals	Causes an uncontrolled release of calcium, leading to severe muscle rigidity, fever, and metabolic crisis.	Can cause exertional rhabdomyolysis and heat illness due to similar physiological stressors.
Associated Medications	Only specific inhaled gases and the muscle relaxant succinylcholine are definitive triggers.	Some statin drugs have been reported to trigger myopathic symptoms in susceptible individuals, suggesting a potential link.

Prevention and Screening for Malignant Hyperthermia Susceptibility

Preventing a malignant hyperthermia episode starts with identifying at-risk individuals. The screening process involves a combination of gathering family history, clinical evaluation, and specific diagnostic tests.

Detailed Family History: An anesthesiologist or genetic counselor will take a thorough family history, specifically asking about any complications during anesthesia or unexplained anesthetic deaths.
Genetic Testing: A blood sample can be used to test for known genetic mutations, such as in the RYR1 gene, which are linked to MHS.
Muscle Biopsy: The gold standard for diagnosis is the In Vitro Contracture Test (IVCT), which involves a muscle biopsy to test the muscle tissue's reaction to triggering agents in a controlled lab setting. This is typically done at specialized centers.

Conclusion: Recognizing the Risk is Key

While malignant hyperthermia is a rare occurrence, its potential consequences make it crucial to identify susceptible individuals before a surgical procedure. Genetic predisposition, evidenced by a family history of MHS, is the most significant risk factor. However, associated muscle diseases and unexplained episodes of rhabdomyolysis also point to an increased risk. By understanding the risk factors and undergoing appropriate screening, individuals with MHS can be protected by using alternative, non-triggering anesthetic agents. Awareness, and clear communication with healthcare providers, are essential for preventing a life-threatening episode. For more information, the Malignant Hyperthermia Association of the United States (MHAUS) provides comprehensive resources and support for patients and healthcare professionals at their website.

Prevention Strategies for At-Risk Individuals

Individuals identified as susceptible to malignant hyperthermia should take several precautions:

Medical Alert Identification: Wearing a medical alert bracelet or necklace that specifies MHS is vital for alerting healthcare providers in an emergency.
Inform Medical Team: Always inform your surgeon, anesthesiologist, and any medical personnel of your MHS status prior to any procedure involving anesthesia.
Emergency Preparedness: Confirm with your surgical facility that they have dantrolene, the specific antidote for an MH crisis, readily available.
Avoid Triggers: Avoid known triggering agents, and be aware of non-anesthetic triggers like intense exercise in high heat.
Review Anesthetic Plan: Discuss the use of non-triggering anesthetics with your care team well before any surgery.
Educate Family Members: Because of the hereditary nature, it is important to inform close relatives of their potential risk so they can be screened as well.

Frequently Asked Questions

No, malignant hyperthermia is not an allergy. It is an inherited genetic disorder of the muscle cells that causes an abnormal reaction to certain medications, most commonly specific anesthetic gases and the muscle relaxant succinylcholine.

Malignant hyperthermia susceptibility (MHS) is inherited in an autosomal dominant pattern. If one parent has the gene mutation, their children have a 50% chance of inheriting the gene and being susceptible.

No. Not every person with a gene mutation linked to MHS will have a reaction upon every exposure to a trigger. Some susceptible individuals may have had previous uneventful surgeries with triggering agents before experiencing a crisis.

Diagnosis is typically confirmed through genetic testing for mutations in genes like RYR1, or through a more invasive muscle biopsy and contracture test, which is considered the gold standard.

Yes, although it's rare, some susceptible individuals can experience a hypermetabolic state (awake malignant hyperthermia) triggered by non-anesthetic factors such as intense physical exertion in high heat or humidity.

Before surgery, a susceptible individual must inform their entire medical team of their MHS status. They should also wear a medical alert bracelet and confirm that the facility has the antidote, dantrolene, readily available.

Anesthesiologists can use alternative, non-triggering anesthetic agents for susceptible individuals. This includes total intravenous anesthetic techniques and regional anesthesia options like epidurals or nerve blocks.