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Malignant hyperthermia susceptibility type 5(MHS5)

MedGen UID:
418958
Concept ID:
C2930984
Pathologic Function
Synonyms: CACNA1S-Related Malignant Hyperthermia Susceptibility; Malignant hyperpyrexia susceptibility type 5; MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 5; MHS5
 
Gene (location): CACNA1S (1q32.1)
OMIM®: 601887

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 release calcium stores from the sarcoplasmic reticulum and may promote entry of calcium from 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 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 affected individuals 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 description

From GHR
Malignant hyperthermia is a severe reaction to particular 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, and with a muscle relaxant that is used to temporarily paralyze a person during a surgical procedure. If given these drugs, people at risk for malignant hyperthermia may experience muscle rigidity, breakdown of muscle fibers (rhabdomyolysis), a high fever, increased acid levels in the blood and other tissues (acidosis), and a rapid heart rate. Without prompt treatment, the complications of malignant hyperthermia can be life-threatening.People at increased risk for this disorder are said to have malignant hyperthermia susceptibility. Affected individuals may never know they have the condition unless they undergo testing or have a severe reaction to anesthesia during a surgical procedure. While this condition often occurs in people without other serious medical problems, certain inherited muscle diseases (including central core disease and multiminicore disease) are associated with malignant hyperthermia susceptibility.  https://ghr.nlm.nih.gov/condition/malignant-hyperthermia

Recent clinical studies

Etiology

Gonsalves SG, Ng D, Johnston JJ, Teer JK, Stenson PD, Cooper DN, Mullikin JC, Biesecker LG; NISC Comparative Sequencing Program.
Anesthesiology 2013 Nov;119(5):1043-53. doi: 10.1097/ALN.0b013e3182a8a8e7. PMID: 24195946Free PMC Article
von Breunig F, Wappler F, Hagel C, von Richthofen V, Fiege M, Weisshorn R, Stavrou D, Schulte am Esch J
Anesthesiology 2004 Apr;100(4):789-94. PMID: 15087612
Fiege M, Wappler F, Scholz J, Weisshorn R, von Richthofen V, Schulte am Esch J
J Clin Anesth 2000 Mar;12(2):123-8. PMID: 10818326
Figarella-Branger D, Kozak-Ribbens G, Rodet L, Aubert M, Borsarelli J, Cozzone PJ, Pellissier JF
Neuromuscul Disord 1993 Sep-Nov;3(5-6):553-6. PMID: 8186710
Fishbein WN, Muldoon SM, Deuster PA, Armbrustmacher VW
Biochem Med 1985 Dec;34(3):344-54. PMID: 4096721

Diagnosis

Gonsalves SG, Ng D, Johnston JJ, Teer JK, Stenson PD, Cooper DN, Mullikin JC, Biesecker LG; NISC Comparative Sequencing Program.
Anesthesiology 2013 Nov;119(5):1043-53. doi: 10.1097/ALN.0b013e3182a8a8e7. PMID: 24195946Free PMC Article
Brandom BW, Bina S, Wong CA, Wallace T, Visoiu M, Isackson PJ, Vladutiu GD, Sambuughin N, Muldoon SM
Anesth Analg 2013 May;116(5):1078-86. Epub 2013 Apr 4 doi: 10.1213/ANE.0b013e31828a71ff. PMID: 23558838Free PMC Article
Tammaro A, Di Martino A, Bracco A, Cozzolino S, Savoia G, Andria B, Cannavo A, Spagnuolo M, Piluso G, Aurino S, Nigro V
Clin Genet 2011 May;79(5):438-47. doi: 10.1111/j.1399-0004.2010.01493.x. PMID: 20681998
Islander G, Rydenfelt K, Ranklev E, Bodelsson M
Acta Anaesthesiol Scand 2007 May;51(5):614-20. doi: 10.1111/j.1399-6576.2007.01293.x. PMID: 17430325
Yang T, Riehl J, Esteve E, Matthaei KI, Goth S, Allen PD, Pessah IN, Lopez JR
Anesthesiology 2006 Dec;105(6):1164-75. PMID: 17122579

Therapy

Brandom BW, Bina S, Wong CA, Wallace T, Visoiu M, Isackson PJ, Vladutiu GD, Sambuughin N, Muldoon SM
Anesth Analg 2013 May;116(5):1078-86. Epub 2013 Apr 4 doi: 10.1213/ANE.0b013e31828a71ff. PMID: 23558838Free PMC Article
Labib S, Adnane Berdai M, Abourazzak S, Hida M, Harandou M
Pan Afr Med J 2011;9:33. Epub 2011 Jul 25 PMID: 22355435Free PMC Article
Fiege M, Wappler F, Scholz J, Weisshorn R, von Richthofen V, Schulte am Esch J
J Clin Anesth 2000 Mar;12(2):123-8. PMID: 10818326
Hogan K
Curr Opin Neurol 1998 Oct;11(5):469-76. PMID: 9847996

Prognosis

Gonsalves SG, Ng D, Johnston JJ, Teer JK, Stenson PD, Cooper DN, Mullikin JC, Biesecker LG; NISC Comparative Sequencing Program.
Anesthesiology 2013 Nov;119(5):1043-53. doi: 10.1097/ALN.0b013e3182a8a8e7. PMID: 24195946Free PMC Article
Islander G, Rydenfelt K, Ranklev E, Bodelsson M
Acta Anaesthesiol Scand 2007 May;51(5):614-20. doi: 10.1111/j.1399-6576.2007.01293.x. PMID: 17430325
Kindler CH, Girard T, Gong D, Urwyler A
Anesth Analg 2002 Apr;94(4):1028-33, table of contents. PMID: 11916818
Nagarajan K, Fishbein WN, Muldoon SM, Pezeshkpour G
Anesthesiology 1987 May;66(5):680-5. PMID: 3578882
Fishbein WN, Muldoon SM, Deuster PA, Armbrustmacher VW
Biochem Med 1985 Dec;34(3):344-54. PMID: 4096721

Clinical prediction guides

Gonsalves SG, Ng D, Johnston JJ, Teer JK, Stenson PD, Cooper DN, Mullikin JC, Biesecker LG; NISC Comparative Sequencing Program.
Anesthesiology 2013 Nov;119(5):1043-53. doi: 10.1097/ALN.0b013e3182a8a8e7. PMID: 24195946Free PMC Article
Brandom BW, Bina S, Wong CA, Wallace T, Visoiu M, Isackson PJ, Vladutiu GD, Sambuughin N, Muldoon SM
Anesth Analg 2013 May;116(5):1078-86. Epub 2013 Apr 4 doi: 10.1213/ANE.0b013e31828a71ff. PMID: 23558838Free PMC Article
Tammaro A, Di Martino A, Bracco A, Cozzolino S, Savoia G, Andria B, Cannavo A, Spagnuolo M, Piluso G, Aurino S, Nigro V
Clin Genet 2011 May;79(5):438-47. doi: 10.1111/j.1399-0004.2010.01493.x. PMID: 20681998
Islander G, Rydenfelt K, Ranklev E, Bodelsson M
Acta Anaesthesiol Scand 2007 May;51(5):614-20. doi: 10.1111/j.1399-6576.2007.01293.x. PMID: 17430325
von Breunig F, Wappler F, Hagel C, von Richthofen V, Fiege M, Weisshorn R, Stavrou D, Schulte am Esch J
Anesthesiology 2004 Apr;100(4):789-94. PMID: 15087612

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