Details of Disease

General Information of Disease (ID: DISYC9XI)

• Disease Name: Malignant hyperthermia of anesthesia
• Synonyms: anaesthesia related hyperthermia; malignant hyperpyrexia; malignant hyperthermia of anesthesia; malignant hyperthermia syndrome; malignant hyperpyrexia due to anesthesia; malignant hyperpyrexia due to anaesthesia; hyperthermia of anaesthesia; anesthesia related hyperthermia; hyperthermia of anesthesia; malignant hyperthermia
• Definition: A pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anesthetic gasses such as halothane, sevoflurane, desflurane and the depolarizing muscle relaxant succinylcholine, and rarely, to stresses such as vigorous exercise and heat.
• Disease Hierarchy:
  DISLG2RO: Hereditary neuromuscular disease
  DISI6CLK: Muscular channelopathy
  DISYC9XI: Malignant hyperthermia of anesthesia
• Disease Identifiers:
  MONDO ID: MONDO_0018493
  MESH ID: D008305
  UMLS CUI: C0024591
  MedGen ID: 9867
  Orphanet ID: 423
  SNOMED CT ID: 213026003

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 8 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
SCN4A	TT84DRB	Limited	Genetic Variation	[1]
CACNA1S	TT94HRF	Disputed	Genetic Variation	[2]
RYR1	TTU5CIX	Supportive	Autosomal dominant	[3]
CACNA2D1	TTFK1JQ	Strong	Biomarker	[4]
EPHA3	TTHS2LR	Strong	Genetic Variation	[5]
HAL	TTXQOZW	Strong	Genetic Variation	[6]
HTR3A	TTPC4TU	Strong	Biomarker	[7]
KCNA1	TTS3DIK	Strong	Genetic Variation	[8]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC24A3	DTO18LP	Strong	Biomarker	[9]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
PRODH	DEVJIHS	Strong	Genetic Variation	[10]

This Disease Is Related to 12 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ATP2A1	OT959A3A	Limited	Altered Expression	[11]
RYR1	OTWUB65S	Supportive	Autosomal dominant	[3]
CASQ1	OTAY8WOO	Strong	Biomarker	[12]
EIF3K	OTGTKVGO	Strong	Genetic Variation	[13]
GYPB	OTESHUIX	Strong	Genetic Variation	[14]
GYPE	OTBHAG6A	Strong	Genetic Variation	[14]
MEPE	OTXJRUW0	Strong	Genetic Variation	[15]
QDPR	OTSKOIUX	Strong	Genetic Variation	[16]
RYR2	OT0PF19E	Strong	Genetic Variation	[17]
SELENON	OTSGKO5M	Strong	Genetic Variation	[18]
SNRNP27	OTNWI55E	Strong	Genetic Variation	[19]
STAC3	OTPY3BGK	Strong	Biomarker	[20]

References

• [1] Linkage of malignant hyperthermia and hyperkalemic periodic paralysis to the adult skeletal muscle sodium channel (SCN4A) gene in a large pedigree.Am J Med Genet. 1998 Feb 26;76(1):21-7.
• [2] Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for the Use of Potent Volatile Anesthetic Agents and Succinylcholine in the Context of RYR1 or CACNA1S Genotypes.Clin Pharmacol Ther. 2019 Jun;105(6):1338-1344. doi: 10.1002/cpt.1319. Epub 2019 Jan 24.
• [3] Malignant Hyperthermia Susceptibility. 2003 Dec 19 [updated 2020 Jan 16]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
• [4] Genomic structure and functional expression of a human alpha(2)/delta calcium channel subunit gene (CACNA2).Genomics. 1999 Oct 15;61(2):201-9. doi: 10.1006/geno.1999.5941.
• [5] Ca2+ signaling in HEK-293 and skeletal muscle cells expressing recombinant ryanodine receptors harboring malignant hyperthermia and central core disease mutations.J Biol Chem. 2005 Apr 15;280(15):15380-9. doi: 10.1074/jbc.M410421200. Epub 2005 Feb 2.
• [6] The human ryanodine receptor gene: its mapping to 19q13.1, placement in a chromosome 19 linkage group, and exclusion as the gene causing myotonic dystrophy.Am J Hum Genet. 1990 Jun;46(6):1082-9.
• [7] Ondansetron-induced muscular contractures in malignant hyperthermia-susceptible individuals.Anesth Analg. 2012 Oct;115(4):925-8. doi: 10.1213/ANE.0b013e31825d3749. Epub 2012 Jun 13.
• [8] A novel KCNA1 mutation in a family with episodic ataxia and malignant hyperthermia.Neurogenetics. 2016 Oct;17(4):245-249. doi: 10.1007/s10048-016-0486-0. Epub 2016 Jun 8.
• [9] Overactivation of the sodium-calcium exchanger and transient receptor potential in anesthesia-induced malignant hyperthermia.IUBMB Life. 2019 Dec;71(12):2048-2054. doi: 10.1002/iub.2138. Epub 2019 Aug 5.
• [10] Malignant hyperthermia: a pharmacogenetic disease of Ca++ regulating proteins.Curr Mol Med. 2002 Jun;2(4):347-69. doi: 10.2174/1566524023362429.
• [11] Measurement of resting cytosolic Ca2+ concentrations and Ca2+ store size in HEK-293 cells transfected with malignant hyperthermia or central core disease mutant Ca2+ release channels.J Biol Chem. 1999 Jan 8;274(2):693-702. doi: 10.1074/jbc.274.2.693.
• [12] Estrogens Protect Calsequestrin-1 Knockout Mice from Lethal Hyperthermic Episodes by Reducing Oxidative Stress in Muscle.Oxid Med Cell Longev. 2017;2017:6936897. doi: 10.1155/2017/6936897. Epub 2017 Sep 10.
• [13] Exclusion of defects in the skeletal muscle specific regions of the DHPR alpha 1 subunit as frequent causes of malignant hyperthermia.J Med Genet. 1995 Nov;32(11):913-4. doi: 10.1136/jmg.32.11.913.
• [14] A linkage study of malignant hyperthermia (MH).Clin Genet. 1990 Mar;37(3):221-5. doi: 10.1111/j.1399-0004.1990.tb03506.x.
• [15] Polymorphisms and deduced amino acid substitutions in the coding sequence of the ryanodine receptor (RYR1) gene in individuals with malignant hyperthermia.Genomics. 1992 Aug;13(4):1247-54. doi: 10.1016/0888-7543(92)90042-q.
• [16] Dynamic alterations in myoplasmic Ca2+ in malignant hyperthermia and central core disease.Biochem Biophys Res Commun. 2004 Oct 1;322(4):1256-66. doi: 10.1016/j.bbrc.2004.08.031.
• [17] Reduced threshold for store overload-induced Ca(2+) release is a common defect of RyR1 mutations associated with malignant hyperthermia and central core disease.Biochem J. 2017 Aug 7;474(16):2749-2761. doi: 10.1042/BCJ20170282.
• [18] Multi-minicore Disease.Orphanet J Rare Dis. 2007 Jul 13;2:31. doi: 10.1186/1750-1172-2-31.
• [19] The differential effect of halothane and 1,2-dichlorohexafluorocyclobutane on in vitro muscle contractures of patients susceptible to malignant hyperthermia.Anesth Analg. 2002 Apr;94(4):1028-33, table of contents. doi: 10.1097/00000539-200204000-00048.
• [20] Genetic epidemiology of malignant hyperthermia in the UK.Br J Anaesth. 2018 Oct;121(4):944-952. doi: 10.1016/j.bja.2018.06.028. Epub 2018 Aug 17.