U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Malignant hyperthermia, susceptibility to

MedGen UID:
1728755
Concept ID:
C5437603
Finding
Synonym: Malignant hyperthermia susceptibility
SNOMED CT: Malignant hyperthermia genetic susceptibility (890189007); Genetic susceptibility to malignant hyperthermia (890189007)
 
Related genes: RYR1, CACNA1S
 
Monarch Initiative: MONDO:0800188
OMIM® Phenotypic series: PS145600

Disease characteristics

Excerpted from the GeneReview: Malignant Hyperthermia Susceptibility
Malignant hyperthermia susceptibility (MHS) is a pharmacogenetic disorder of skeletal muscle calcium regulation associated with uncontrolled skeletal muscle hypermetabolism. Manifestations of malignant hyperthermia (MH) are precipitated by certain volatile anesthetics (i.e., halothane, isoflurane, sevoflurane, desflurane, enflurane), either alone or in conjunction with a depolarizing muscle relaxant (specifically, succinylcholine). The triggering substances cause uncontrolled release of calcium from the sarcoplasmic reticulum and may promote entry of extracellular calcium into the myoplasm, causing contracture of skeletal muscles, glycogenolysis, and increased cellular metabolism, resulting in production of heat and excess lactate. Affected individuals experience acidosis, hypercapnia, tachycardia, hyperthermia, muscle rigidity, compartment syndrome, rhabdomyolysis with subsequent increase in serum creatine kinase (CK) concentration, hyperkalemia with a risk for cardiac arrhythmia or even cardiac arrest, and myoglobinuria with a risk for renal failure. In nearly all cases, the first manifestations of MH (tachycardia and tachypnea) occur in the operating room; however, MH may also occur in the early postoperative period. There is mounting evidence that some individuals with MHS will also develop MH with exercise and/or on exposure to hot environments. Without proper and prompt treatment with dantrolene sodium, mortality is extremely high. [from GeneReviews]
Authors:
Henry Rosenberg  |  Nyamkhishig Sambuughin  |  Sheila Riazi, et. al.   view full author information

Additional descriptions

From PharmGKB
Malignant hyperthermia susceptibility (MHS) is a predisposition to a potentially life-threatening, hypermetabolic reaction triggered by potent volatile anesthetics (i.e. desflurane, enflurane, halothane, isoflurane, methoxyflurane, and sevoflurane) or the depolarizing muscle relaxant succinylcholine. These agents are relatively contraindicated in persons with MHS. MHS is diagnosed either by a positive response to the in vitro contracture test (IVCT) or the caffeine-halothane contracture test (CHCT), or by the presence of a pathogenic variant in RYR1 or CACNA1S that has been identified as causative for MHS (PMID: 30499100). Absence of pathogenetic variants in RYR1 or CACNA1S does not eliminate the chance of MHS based on findings that the genetic cause remains unknown for about half of all MH survivors, with contracture test-confirmed MHS (PMID: 28902675). Both genes are included on the list of actionable secondary findings by the American College of Medical Genetics and Genomics. MHS is inherited in an autosomal dominant manner and a positive result for a patient has familial ramifications. In addition to potential variations in RYR1 or CACNA1S, personal or family history of a reaction to these drugs or agents needs to be considered. Therapeutic guidelines for the use of potent volatile anesthetic agents and succinylcholine in the context of RYR1 or CACNA1S genotypes have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC).  https://www.pharmgkb.org/guidelineAnnotation/PA166180457
From OMIM
Susceptibility to malignant hyperthermia (MHS), a skeletal muscle disorder most often inherited as an autosomal dominant trait, is one of the main causes of death due to anesthesia. In susceptible people, a malignant hyperthermia episode is triggered by exposure to commonly used volatile anesthetic agents such as halothane or depolarizing muscle relaxants such as succinyl choline. A fulminant MH crisis is characterized by any combination of hyperthermia, skeletal muscle rigidity, tachycardia or arrhythmia, respiratory and metabolic acidosis, and rhabdomyolysis. Except for this susceptibility to triggering agents, MHS patients are not clinically distinguishable from the general population (summary by Monnier et al., 1997). Genetic Heterogeneity of Susceptibility to Malignant Hyperthermia Other MHS loci include MHS2 (154275) on chromosome 17q; MHS3 (154276) on chromosome 7q; MHS4 (600467) on chromosome 3q; MHS5 (601887), caused by mutation in the CACNA1S gene (114208) on chromosome 1q32; and MHS6 (601888) on chromosome 5p.  http://www.omim.org/entry/145600

Professional guidelines

Recent clinical studies

Etiology

Islander G, Twetman ER
Anesth Analg 1999 May;88(5):1155-60. doi: 10.1097/00000539-199905000-00035. PMID: 10320187
Larach MG, Landis JR, Bunn JS, Diaz M
Anesthesiology 1992 Jan;76(1):16-27. doi: 10.1097/00000542-199201000-00003. PMID: 1729931

Diagnosis

Islander G, Twetman ER
Anesth Analg 1999 May;88(5):1155-60. doi: 10.1097/00000539-199905000-00035. PMID: 10320187
Larach MG, Landis JR, Bunn JS, Diaz M
Anesthesiology 1992 Jan;76(1):16-27. doi: 10.1097/00000542-199201000-00003. PMID: 1729931
Mitsumoto H
Cleve Clin J Med 1989 Nov-Dec;56(8):754-5. doi: 10.3949/ccjm.56.8.754. PMID: 2605774

Therapy

Larach MG, Landis JR, Bunn JS, Diaz M
Anesthesiology 1992 Jan;76(1):16-27. doi: 10.1097/00000542-199201000-00003. PMID: 1729931

Prognosis

Larach MG, Landis JR, Bunn JS, Diaz M
Anesthesiology 1992 Jan;76(1):16-27. doi: 10.1097/00000542-199201000-00003. PMID: 1729931

Clinical prediction guides

Larach MG, Landis JR, Bunn JS, Diaz M
Anesthesiology 1992 Jan;76(1):16-27. doi: 10.1097/00000542-199201000-00003. PMID: 1729931

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • ACMG ACT, 2019
      American College of Medical Genetics and Genomics, Genomic Testing (Secondary Findings) ACT Sheet, RYR1 and CACNA1S Pathogenic Variants (Malignant Hyperthermia), 2019
    • Orphanet, 2013
      Orphanet Emergency Guidelines: Malignant hyperthermia

    Consumer resources

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...