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<span>Malignant hyperthermia</span>
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<span class="page-url print-only">URL of this page: https://medlineplus.gov/genetics/condition/malignant-hyperthermia/</span>
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<article>
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<h1>Malignant hyperthermia</h1>
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<div class="mp-exp exp-full" data-bookmark="description">
<h2>Description</h2>
<section><div class="mp-content"><p>Malignant hyperthermia is a severe reaction to particular anesthetic drugs that are often used during surgery and other invasive procedures. Specifically, this reaction occurs in response to some anesthetic gases, which are used to block the sensation of pain, either given alone or in combination with a muscle relaxant that is used to temporarily paralyze a person during a surgical procedure. If given these drugs, people at risk of malignant hyperthermia may experience a rapid increase in heart rate and body temperature (hyperthermia), abnormally fast breathing, muscle rigidity, breakdown of <a class="image-modal" data-alt="The components of the muscle fiber, which is made up of multiple myofibrils." data-caption="" data-credit="Designua/Shutterstock.com" data-filepath="images/PX0000Y4_PRESENTATION.jpeg" data-imgtype="genetics" data-pix="PX0000Y4" data-sourceurl="" data-title="Skeletal muscle fiber" href="https://medlineplus.gov/images/PX0000Y4_PRESENTATION.jpeg" id="PX0000Y4_1" title="Show image">muscle fibers<img alt="" aria-hidden="true" class="image-modal-icon" src="https://medlineplus.gov/css/img/icon_camera_small.png"/></a> (rhabdomyolysis), and increased acid levels in the blood and other tissues (acidosis). Without prompt treatment and cessation of the drugs, the body's reaction can cause multiple organs to be unable to function, including the heart (cardiac arrest) and kidneys (renal failure), and it can cause a blood clotting abnormality called disseminated intravascular coagulation. These complications may be life-threatening. (In medicine, the term malignant refers to conditions that are dangerous to one's health.)</p><p>People at increased risk of this disorder are said to have malignant hyperthermia susceptibility. Affected individuals may never know they have the condition unless they have a severe reaction to anesthesia during a surgical procedure or they undergo testing (for instance, if susceptibility is suspected because a family member had a severe reaction). Malignant hyperthermia may not occur every time anesthesia is used. Many individuals who develop a severe reaction have previously been exposed to a triggering drug and not had a reaction.</p><p>Affected individuals may be at increased risk for "awake" malignant hyperthermia, in which the severe reaction occurs in response to physical activity, often while sick, rather than in reaction to exposure to a triggering drug.</p><p>While malignant hyperthermia often occurs in people without other serious medical problems, certain inherited muscle diseases (including <a data-pid="14861" href="https://medlineplus.gov/genetics/condition/central-core-disease/">central core disease</a>, <a data-pid="14865" href="https://medlineplus.gov/genetics/condition/multiminicore-disease/">multiminicore disease</a>, and <a data-pid="17005" href="https://medlineplus.gov/genetics/condition/stac3-disorder/">STAC3 disorder</a>) are associated with malignant hyperthermia susceptibility.</p></div>
</section>
</div>
<div class="mp-exp exp-full" data-bookmark="frequency">
<h2>Frequency</h2>
<section><div class="mp-content"><p>Malignant hyperthermia occurs in 1 in 5,000 to 50,000 instances in which people are given anesthetic gases. Susceptibility to malignant hyperthermia is probably more frequent, because many people with an increased risk of this condition are never exposed to drugs that would trigger a reaction and bring them to medical attention.</p></div>
</section>
</div>
<div class="mp-exp exp-full" data-bookmark="causes">
<h2>Causes</h2>
<section><div class="mp-content"><p>Certain variations of the <i><a data-pid="17775" href="https://medlineplus.gov/genetics/gene/ryr1/">RYR1</a></i> and <i><a data-pid="17687" href="https://medlineplus.gov/genetics/gene/cacna1s/">CACNA1S</a></i> genes increase the risk of developing malignant hyperthermia. Mutations in the <i>RYR1</i> gene account for most cases of malignant hyperthermia susceptibility, while mutations in the <i>CACNA1S</i> gene cause less than 1 percent of all cases of malignant hyperthermia susceptibility.</p><p>The <i>RYR1</i> and <i>CACNA1S</i> genes provide instructions for making proteins that play essential roles in muscles used for movement (<a class="image-modal" data-alt="Diagram showing structure of skeletal muscles" data-caption="" data-credit="sciencepics/Shutterstock.com" data-filepath="images/PX00019C_PRESENTATION.jpeg" data-imgtype="genetics" data-pix="PX00019C" data-sourceurl="" data-title="Skeletal muscle anatomy" href="https://medlineplus.gov/images/PX00019C_PRESENTATION.jpeg" id="PX00019C_3" title="Show image">skeletal muscles<img alt="" aria-hidden="true" class="image-modal-icon" src="https://medlineplus.gov/css/img/icon_camera_small.png"/></a>). For the body to move normally, these muscles must tense (contract) and relax in a coordinated way. Muscle contractions are triggered by the flow of certain charged atoms (ions) in muscle cells. The proteins produced from the <i>RYR1</i> and <i>CACNA1S</i> genes are involved in the movement of calcium ions within muscle cells. In response to certain signals, the CACNA1S protein helps turn on (activate) the RYR1 channel. When the RYR1 channel is active, it releases calcium ions from storage into the fluid-filled space inside muscle cells. The resulting increase in calcium ion concentration inside the cells stimulates muscles to contract.</p><p>Mutations in the <i>RYR1</i> or <i>CACNA1S</i> gene cause the RYR1 channel to open more easily and close more slowly in response to certain drugs. As a result, abnormally large amounts of calcium ions are released from storage within muscle cells. The abnormal increase in calcium ion concentration within muscle cells activates processes that generate heat (leading to increased body temperature) and produce excess acid (leading to acidosis). An overabundance of calcium ions also causes skeletal muscles to contract, which leads to muscle rigidity.</p><p>Up to half of people with malignant hyperthermia susceptibility do not have a mutation in one of the known genes. The causes of these cases are still under study.</p></div>
</section>
<section>
<div class="related-genes mp-exp exp-full">
<h3>Learn more about the genes associated with Malignant hyperthermia</h3>
<ul class="relatedmp">
<li><a href="https://medlineplus.gov/genetics/gene/cacna1s/">CACNA1S</a></li>
<li><a href="https://medlineplus.gov/genetics/gene/ryr1/">RYR1</a></li>
</ul>
</div>
</section>
</div>
<div class="mp-exp exp-full" data-bookmark="inheritance">
<h2>Inheritance</h2>
<section><div class="mp- mp-content"><p>Malignant hyperthermia susceptibility is inherited in an <a class="image-modal" data-alt="A parent with an autosomal dominant condition passes the altered gene to two affected children. Two other children do not receive the altered gene, and are unaffected." data-caption="" data-credit="U.S. National Library of Medicine" data-filepath="images/PX00009C_PRESENTATION.jpeg" data-imgtype="genetics" data-pix="PX00009C" data-sourceurl="" data-title="Autosomal dominant inheritance" href="https://medlineplus.gov/images/PX00009C_PRESENTATION.jpeg" id="PX00009C_1" title="Show image">autosomal dominant pattern<img alt="" aria-hidden="true" class="image-modal-icon" src="https://medlineplus.gov/css/img/icon_camera_small.png"/></a>, which means one copy of the altered gene in each cell is sufficient to increase the risk of a severe reaction to certain drugs used during surgery. In most cases, an affected person inherits the altered gene from a parent who is also at risk for the condition.</p></div>
</section>
</div>
<div class="mp-exp exp-full" data-bookmark="synonyms">
<h2>Other Names for This Condition</h2>
<section>
<ul class="bulletlist">
<li>Anesthesia related hyperthermia</li> <li>Hyperpyrexia, malignant</li> <li>Hyperthermia, malignant</li> <li>Malignant hyperpyrexia</li> <li>MHS</li>
</ul>
</section>
</div>
<div class="mp-exp exp-full" data-bookmark="resources">
<h2>Additional Information & Resources</h2>
<section>
<div class="mp-content">
<h2>Genetic Testing Information</h2>
<ul>
<li><a href="https://www.ncbi.nlm.nih.gov/gtr/conditions/C2930980/" target="TheNewWin">Genetic Testing Registry: Malignant hyperthermia, susceptibility to, 1</a> <span class="desc-text"><img alt="From the National Institutes of Health" title="From the National Institutes of Health" src="https://medlineplus.gov/images/nih.png" class="imgdesc" width="25" height="16"></span></li>
<li><a href="https://www.ncbi.nlm.nih.gov/gtr/conditions/C1838102/" target="TheNewWin">Genetic Testing Registry: Malignant hyperthermia, susceptibility to, 4</a> <span class="desc-text"><img alt="From the National Institutes of Health" title="From the National Institutes of Health" src="https://medlineplus.gov/images/nih.png" class="imgdesc" width="25" height="16"></span></li>
<li><a href="https://www.ncbi.nlm.nih.gov/gtr/conditions/C1866077/" target="TheNewWin">Genetic Testing Registry: Malignant hyperthermia, susceptibility to, 5</a> <span class="desc-text"><img alt="From the National Institutes of Health" title="From the National Institutes of Health" src="https://medlineplus.gov/images/nih.png" class="imgdesc" width="25" height="16"></span></li>
<li><a href="https://www.ncbi.nlm.nih.gov/gtr/conditions/C1866076/" target="TheNewWin">Genetic Testing Registry: Malignant hyperthermia, susceptibility to, 6</a> <span class="desc-text"><img alt="From the National Institutes of Health" title="From the National Institutes of Health" src="https://medlineplus.gov/images/nih.png" class="imgdesc" width="25" height="16"></span></li>
</ul>
</div>
</section>
<section>
<div class="mp-content">
<h2>Genetic and Rare Diseases Information Center</h2>
<ul>
<li><a href="https://rarediseases.info.nih.gov/diseases/8433/index" target="TheNewWin">King-Denborough syndrome</a> <span class="desc-text"><img alt="From the National Institutes of Health" title="From the National Institutes of Health" src="https://medlineplus.gov/images/nih.png" class="imgdesc" width="25" height="16"></span></li>
<li><a href="https://rarediseases.info.nih.gov/diseases/6964/index" target="TheNewWin">Malignant hyperthermia of anesthesia</a> <span class="desc-text"><img alt="From the National Institutes of Health" title="From the National Institutes of Health" src="https://medlineplus.gov/images/nih.png" class="imgdesc" width="25" height="16"></span></li>
</ul>
</div>
</section>
<section>
<div class="mp-content">
<h2>Patient Support and Advocacy Resources</h2>
<ul>
<li><a href="https://rarediseases.org/" target="TheNewWin">National Organization for Rare Disorders (NORD)</a></li>
</ul>
</div>
</section>
<section>
<div class="mp-content">
<h2>Clinical Trials</h2>
<ul>
<li><a href="https://clinicaltrials.gov/search?cond=%22Malignant hyperthermia%22" target="TheNewWin">ClinicalTrials.gov</a> <span class="desc-text"><img alt="From the National Institutes of Health" title="From the National Institutes of Health" src="https://medlineplus.gov/images/nih.png" class="imgdesc" width="25" height="16"></span></li>
</ul>
</div>
</section>
<section>
<div class="mp-content">
<h2>Catalog of Genes and Diseases from OMIM</h2>
<ul>
<li><a href="https://omim.org/entry/145600" target="TheNewWin">MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 1; MHS1</a></li>
<li><a href="https://omim.org/entry/154275" target="TheNewWin">MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 2</a></li>
<li><a href="https://omim.org/entry/154276" target="TheNewWin">MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 3</a></li>
<li><a href="https://omim.org/entry/601887" target="TheNewWin">MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 5; MHS5</a></li>
<li><a href="https://omim.org/entry/601888" target="TheNewWin">MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 6</a></li>
<li><a href="https://omim.org/entry/600467" target="TheNewWin">MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 4</a></li>
</ul>
</div>
</section>
<section>
<div class="mp-content">
<h2>Scientific Articles on PubMed</h2>
<ul>
<li><a href="https://pubmed.ncbi.nlm.nih.gov/?term=%28Malignant+Hyperthermia%5BMAJR%5D%29+AND+%28malignant+hyperthermia%5BTIAB%5D%29+AND+english%5Bla%5D+AND+human%5Bmh%5D+AND+%22last+720+days%22%5Bdp%5D" target="TheNewWin">PubMed</a> <span class="desc-text"><img alt="From the National Institutes of Health" title="From the National Institutes of Health" src="https://medlineplus.gov/images/nih.png" class="imgdesc" width="25" height="16"></span></li>
</ul>
</div>
</section>
</div>
<div class="mp-exp exp-full" data-bookmark="references">
<h2>References</h2>
<section>
<div class="mp-content">
<ul>
<li>Ellinas H, Albrecht MA. Malignant Hyperthermia Update. Anesthesiol Clin. 2020
Mar;38(1):165-181. doi: 10.1016/j.anclin.2019.10.010. <a href="https://pubmed.ncbi.nlm.nih.gov/32008650" target="TheNewWin">Citation on PubMed</a></li>
<li>Kraeva N, Sapa A, Dowling JJ, Riazi S. Malignant hyperthermia susceptibility
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