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Malignant hyperthermia, susceptibility to, 3

MedGen UID:
418956
•Concept ID:
C2930982
•
Finding
Synonyms: Malignant hyperpyrexia susceptibility type 3; Malignant hyperthermia susceptibility type 3; MHS3-Related Malignant Hyperthermia Susceptibility
 
Monarch Initiative: MONDO:0007940
OMIM®: 154276

Authors:

Additional description

From OMIM
Malignant hyperthermia susceptibility (MHS) is an autosomal dominant disorder of skeletal muscle which manifests as a potentially fatal hypermetabolic crisis triggered by commonly used anaesthetic agents (summary by Iles et al., 1994). For a phenotypic description and a discussion of genetic heterogeneity of malignant hyperthermia susceptibility, see MHS1 (145600).  http://www.omim.org/entry/154276

Clinical features

From HPO
Hypertonia
MedGen UID:
10132
•Concept ID:
C0026826
•
Finding
A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move.
See: Feature record | Search on this feature
Myopathy
MedGen UID:
10135
•Concept ID:
C0026848
•
Disease or Syndrome
A disorder of muscle unrelated to impairment of innervation or neuromuscular junction.
See: Feature record | Search on this feature
Exercise-induced rhabdomyolysis
MedGen UID:
867168
•Concept ID:
C4021526
•
Finding
Rhabdomyolysis induced by exercise.
See: Feature record | Search on this feature
Alcohol-induced rhabdomyolysis
MedGen UID:
868941
•Concept ID:
C4023355
•
Finding
Rhabdomyolysis induced by intake of alcohol.
See: Feature record | Search on this feature
Anesthetic-induced rhabdomylosis
MedGen UID:
868942
•Concept ID:
C4023356
•
Disease or Syndrome
Rhabdomyolysis induced by anesthesia.
See: Feature record | Search on this feature
Viral infection-induced rhabdomyolysis
MedGen UID:
871126
•Concept ID:
C4025595
•
Disease or Syndrome
Rhabdomyolysis induced by a viral infection.
See: Feature record | Search on this feature
Lactic acidosis
MedGen UID:
1717
•Concept ID:
C0001125
•
Disease or Syndrome
An abnormal buildup of lactic acid in the body, leading to acidification of the blood and other bodily fluids.
See: Feature record | Search on this feature
Fever
MedGen UID:
5169
•Concept ID:
C0015967
•
Sign or Symptom
Body temperature elevated above the normal range.
See: Feature record | Search on this feature
Hyperkalemia
MedGen UID:
5691
•Concept ID:
C0020461
•
Finding
An abnormally increased potassium concentration in the blood.
See: Feature record | Search on this feature
Hyperphosphatemia
MedGen UID:
39326
•Concept ID:
C0085681
•
Disease or Syndrome
An abnormally increased phosphate concentration in the blood.
See: Feature record | Search on this feature
Elevated circulating creatine kinase concentration
MedGen UID:
69128
•Concept ID:
C0241005
•
Finding
An elevation of the level of the enzyme creatine kinase (also known as creatine phosphokinase (CK; EC 2.7.3.2) in the blood. CK levels can be elevated in a number of clinical disorders such as myocardial infarction, rhabdomyolysis, and muscular dystrophy.
See: Feature record | Search on this feature
Malignant hyperthermia
MedGen UID:
1830388
•Concept ID:
C5779784
•
Pathologic Function
Malignant hyperthermia is characterized by a rapid increase in temperature to 39-42 degrees C. Malignant hyperthermia may occur in response to either inhalational anesthetics such as halothane, to muscle relaxants such as succinylcholine, or to exercise.
See: Feature record | Search on this feature
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Professional guidelines

PubMed

Physician-directed genetic screening to evaluate personal risk for medically actionable disorders: a large multi-center cohort study.
Haverfield EV, Esplin ED, Aguilar SJ, Hatchell KE, Ormond KE, Hanson-Kahn A, Atwal PS, Macklin-Mantia S, Hines S, Sak CW, Tucker S, Bleyl SB, Hulick PJ, Gordon OK, Velsher L, Gu JYJ, Weissman SM, Kruisselbrink T, Abel C, Kettles M, Slavotinek A, Mendelsohn BA, Green RC, Aradhya S, Nussbaum RL
BMC Med 2021 Aug 18;19(1):199. doi: 10.1186/s12916-021-01999-2. PMID: 34404389Free PMC Article
Consensus Statement of the Malignant Hyperthermia Association of the United States on Unresolved Clinical Questions Concerning the Management of Patients With Malignant Hyperthermia.
Litman RS, Smith VI, Larach MG, Mayes L, Shukry M, Theroux MC, Watt S, Wong CA
Anesth Analg 2019 Apr;128(4):652-659. doi: 10.1213/ANE.0000000000004039. PMID: 30768455
Malignant hyperthermia. Preoperative assessment of risk factors.
Smith RJ
Br J Anaesth 1988 Feb;60(3):317-9. doi: 10.1093/bja/60.3.317. PMID: 3279992

Curated

Orphanet Emergency Guidelines: Malignant hyperthermia

Recent clinical studies

Etiology

Idiopathic hyperCKemia and malignant hyperthermia susceptibility.
Santos JM, Andrade PV, Galleni L, Vainzof M, Sobreira CFR, Schmidt B, Oliveira ASB, Amaral JLG, Silva HCA
Can J Anaesth 2017 Dec;64(12):1202-1210. Epub 2017 Sep 26 doi: 10.1007/s12630-017-0978-x. PMID: 28952030
Malignant hyperthermia.
Rosenberg H, Davis M, James D, Pollock N, Stowell K
Orphanet J Rare Dis 2007 Apr 24;2:21. doi: 10.1186/1750-1172-2-21. PMID: 17456235Free PMC Article
Safety of amide local anesthetics in patients susceptible to malignant hyperthermia.
Dershwitz M, Ryan JF, Guralnick W
J Am Dent Assoc 1989 Mar;118(3):276, 278, 280. doi: 10.14219/jada.archive.1989.0099. PMID: 2646341
Malignant hyperthermia. Preoperative assessment of risk factors.
Smith RJ
Br J Anaesth 1988 Feb;60(3):317-9. doi: 10.1093/bja/60.3.317. PMID: 3279992
Malignant hyperthermia.
Rosenberg H
Hosp Pract (Off Ed) 1985 Mar 15;20(3):139, 144-5, 148 passim. doi: 10.1080/21548331.1985.11703021. PMID: 3932397

Diagnosis

Functional characterization of RYR1 variants identified in malignant hyperthermia susceptible individuals.
Noda Y, Miyoshi H, Benucci S, Gonzalez A, Bandschapp O, Girard T, Treves S, Zorzato F
Neuromuscul Disord 2023 Dec;33(12):951-963. Epub 2023 Nov 3 doi: 10.1016/j.nmd.2023.10.019. PMID: 37996280
Malignant hyperthermia.
Rosenberg H, Davis M, James D, Pollock N, Stowell K
Orphanet J Rare Dis 2007 Apr 24;2:21. doi: 10.1186/1750-1172-2-21. PMID: 17456235Free PMC Article
Malignant hyperthermia. Preoperative assessment of risk factors.
Smith RJ
Br J Anaesth 1988 Feb;60(3):317-9. doi: 10.1093/bja/60.3.317. PMID: 3279992
Diagnosis of susceptibility to malignant hyperthermia in man.
Ording H
Br J Anaesth 1988 Feb;60(3):287-302. doi: 10.1093/bja/60.3.287. PMID: 3279989
Malignant hyperthermia.
Rosenberg H
Hosp Pract (Off Ed) 1985 Mar 15;20(3):139, 144-5, 148 passim. doi: 10.1080/21548331.1985.11703021. PMID: 3932397

Therapy

Pre-operative exercise and pyrexia as modifying factors in malignant hyperthermia (MH).
Riazi S, Bersselaar LRVD, Islander G, Heytens L, Snoeck MMJ, Bjorksten A, Gillies R, Dranitsaris G, Hellblom A, Treves S, Kunst G, Voermans NC, Jungbluth H
Neuromuscul Disord 2022 Aug;32(8):628-634. Epub 2022 Jun 11 doi: 10.1016/j.nmd.2022.06.003. PMID: 35738978
PharmGKB summary: very important pharmacogene information for RYR1.
Alvarellos ML, Krauss RM, Wilke RA, Altman RB, Klein TE
Pharmacogenet Genomics 2016 Mar;26(3):138-44. doi: 10.1097/FPC.0000000000000198. PMID: 26709912Free PMC Article
Malignant hyperthermia.
Rosenberg H, Davis M, James D, Pollock N, Stowell K
Orphanet J Rare Dis 2007 Apr 24;2:21. doi: 10.1186/1750-1172-2-21. PMID: 17456235Free PMC Article
Malignant hyperthermia.
Rosenberg H
Hosp Pract (Off Ed) 1985 Mar 15;20(3):139, 144-5, 148 passim. doi: 10.1080/21548331.1985.11703021. PMID: 3932397
Drug treatment of malignant hyperpyrexia.
Austin KL, Denborough MA
Anaesth Intensive Care 1977 Aug;5(3):207-13. doi: 10.1177/0310057X7700500303. PMID: 900461

Prognosis

Evaluation of Malignant Hyperthermia Features in Patients with Pathogenic or Likely Pathogenic RYR1 Variants Disclosed through a Population Genomic Screening Program.
Yu KD, Betts MN, Urban GM, Schwartz MLB, Robinson TO, Moyer RJ, Taddonio SW, Vasudevan A, Johns A, Sturm AC, Kelly MA, Williams MS, Poler SM, Buchanan AH
Anesthesiology 2024 Jan 1;140(1):52-61. doi: 10.1097/ALN.0000000000004786. PMID: 37787745
Prevalence of malignant hyperthermia diagnosis in obstetric patients in the United States, 2003 to 2014.
Guglielminotti J, Rosenberg H, Li G
BMC Anesthesiol 2020 Jan 20;20(1):19. doi: 10.1186/s12871-020-0934-0. PMID: 31959119Free PMC Article
Malignant hyperthermia in Canada: characteristics of index anesthetics in 129 malignant hyperthermia susceptible probands.
Riazi S, Larach MG, Hu C, Wijeysundera D, Massey C, Kraeva N
Anesth Analg 2014 Feb;118(2):381-387. doi: 10.1213/ANE.0b013e3182937d8b. PMID: 23842196
Hereditary vulnerabilities to post-operative cognitive dysfunction and dementia.
Hogan KJ
Prog Neuropsychopharmacol Biol Psychiatry 2013 Dec 2;47:128-34. Epub 2013 Apr 3 doi: 10.1016/j.pnpbp.2013.02.018. PMID: 23562862
Exertional rhabdomyolysis: a clinical review with a focus on genetic influences.
Landau ME, Kenney K, Deuster P, Campbell W
J Clin Neuromuscul Dis 2012 Mar;13(3):122-36. doi: 10.1097/CND.0b013e31822721ca. PMID: 22538307

Clinical prediction guides

Fatigue, depression, and physical activity in patients with malignant hyperthermia: a cross-sectional observational study.
Andrade PMV, Valim LÍM, Santos JMD, Castro I, Amaral JLGD, Silva HCAD
Braz J Anesthesiol 2023 Mar-Apr;73(2):132-137. Epub 2021 Oct 6 doi: 10.1016/j.bjane.2021.07.038. PMID: 34626754Free PMC Article
Pre-operative exercise and pyrexia as modifying factors in malignant hyperthermia (MH).
Riazi S, Bersselaar LRVD, Islander G, Heytens L, Snoeck MMJ, Bjorksten A, Gillies R, Dranitsaris G, Hellblom A, Treves S, Kunst G, Voermans NC, Jungbluth H
Neuromuscul Disord 2022 Aug;32(8):628-634. Epub 2022 Jun 11 doi: 10.1016/j.nmd.2022.06.003. PMID: 35738978
The histopathological spectrum of malignant hyperthermia and rhabdomyolysis due to RYR1 mutations.
Knuiman GJ, Küsters B, Eshuis L, Snoeck M, Lammens M, Heytens L, De Ridder W, Baets J, Scalco RS, Quinlivan R, Holton J, Bodi I, Wraige E, Radunovic A, von Landenberg C, Reimann J, Kamsteeg EJ, Sewry C, Jungbluth H, Voermans NC
J Neurol 2019 Apr;266(4):876-887. Epub 2019 Feb 20 doi: 10.1007/s00415-019-09209-z. PMID: 30788618Free PMC Article
Idiopathic hyperCKemia and malignant hyperthermia susceptibility.
Santos JM, Andrade PV, Galleni L, Vainzof M, Sobreira CFR, Schmidt B, Oliveira ASB, Amaral JLG, Silva HCA
Can J Anaesth 2017 Dec;64(12):1202-1210. Epub 2017 Sep 26 doi: 10.1007/s12630-017-0978-x. PMID: 28952030
Insulin secretion in malignant hyperpyrexia.
Denborough MA, Warne GL, Moulds RF, Martin FI
Br Med J 1974 Aug 24;3(5929):493-5. doi: 10.1136/bmj.3.5929.493. PMID: 4413915Free PMC Article

Recent systematic reviews

Preclinical model systems of ryanodine receptor 1-related myopathies and malignant hyperthermia: a comprehensive scoping review of works published 1990-2019.
Lawal TA, Wires ES, Terry NL, Dowling JJ, Todd JJ
Orphanet J Rare Dis 2020 May 7;15(1):113. doi: 10.1186/s13023-020-01384-x. PMID: 32381029Free PMC Article

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