Malignant hyperthermia and central core disease causative mutations in Swedish patients

Broman, Marcus; Islander, Gunilla; Müller, C. R.; Ranklev-Twetman, Eva

doi:10.1111/j.1399-6576.2006.01165.x

Cited by 9 publications

(8 citation statements)

References 21 publications

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“…A few families demonstrate autosomal recessive inheritance. Histological examination of affected muscles shows a predominance of type I fibres containing clearly defined areas (cores) lacking oxidative enzyme activity [ 34 – 36 ].…”

Section: Reviewmentioning

confidence: 99%

Malignant hyperthermia: a review

Rosenberg

Pollock

Schiemann

et al. 2015

Orphanet J Rare Dis

435

529

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Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anesthetic gases such as halothane, sevoflurane, desflurane, isoflurane and the depolarizing muscle relaxant succinylcholine, and rarely, in humans, to stressors such as vigorous exercise and heat. The incidence of MH reactions ranges from 1:10,000 to 1: 250,000 anesthetics. However, the prevalence of the genetic abnormalities may be as great as one in 400 individuals. MH affects humans, certain pig breeds, dogs and horses. The classic signs of MH include hyperthermia, tachycardia, tachypnea, increased carbon dioxide production, increased oxygen consumption, acidosis, hyperkalaemia, muscle rigidity, and rhabdomyolysis, all related to a hypermetabolic response. The syndrome is likely to be fatal if untreated. An increase in end-tidal carbon dioxide despite increased minute ventilation provides an early diagnostic clue. In humans the syndrome is inherited in an autosomal dominant pattern, while in pigs it is autosomal recessive. Uncontrolled rise of myoplasmic calcium, which activates biochemical processes related to muscle activation leads to the pathophysiologic changes. In most cases, the syndrome is caused by a defect in the ryanodine receptor. Over 400 variants have been identified in the RYR1 gene located on chromosome 19q13.1, and at least 34 are causal for MH. Less than 1 % of variants have been found in CACNA1S but not all of these are causal. Diagnostic testing involves the in vitro contracture response of biopsied muscle to halothane, caffeine, and in some centres ryanodine and 4-chloro-m-cresol. Elucidation of the genetic changes has led to the introduction of DNA testing for susceptibility to MH. Dantrolene sodium is a specific antagonist and should be available wherever general anesthesia is administered. Increased understanding of the clinical manifestation and pathophysiology of the syndrome, has lead to the mortality decreasing from 80 % thirty years ago to <5 % in 2006.

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Section: Reviewmentioning

confidence: 99%

Malignant hyperthermia: a review

Rosenberg

Pollock

Schiemann

et al. 2015

Orphanet J Rare Dis

435

529

View full text Add to dashboard Cite

show abstract

“…For a number of patients in whom a mutation in the family is known, a genetic mutation analysis test is available (4). In the majority of Scandinavian families, the mutation is not known (5).…”

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confidence: 99%

Male preponderance of patients testing positive for malignant hyperthermia susceptibility

Islander

Rydenfelt

Ranklev

et al. 2007

Acta Anaesthesiol Scand

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“…1 ). 11 All of the RYR1 variants that were pathogenic or likely pathogenic were missense variants, and they included two novel variants: c.5915A>T and c.12250C>T. Four patients (ID25, ID37, ID131, and ID185) carried previously reported pathogenic variants, 12 13 14 among which ID131 carried compound heterozygous variants (c.2287G>A and c.10817T>C). The proband's parents were both clinically healthy.…”

Section: Resultsmentioning

confidence: 99%

Clinical and Pathologic Findings of Korean Patients with RYR1-Related Congenital Myopathy

et al. 2018

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Background and PurposeThis study was designed to investigate clinical and pathologic characteristics of five Korean patients with RYR1-related congenital myopathy (CM).MethodsFive patients from unrelated families were diagnosed with RYR1-related CM via direct or targeted sequencing of RYR1. Their clinical, mutational, and pathologic findings were then analyzed.ResultsSeven different mutations were identified, including two novel mutations: c.5915A>T and c.12250C>T. All of the patients presented at infancy with proximal dominant weakness and delayed motor milestones. Other clinical findings were scoliosis in three patients, winged scapula in two, hip dislocation in one, and pectus excavatum in one. Ophthalmoplegia was observed in one patient with a novel recessive mutation. Two of three muscle specimens revealed a myopathic pattern with core.ConclusionsWe have identified a novel compound heterozygous RYR1 mutation and demonstrated clinical and pathologic findings in five Korean patients with RYR1-related CM.

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Malignant hyperthermia and central core disease causative mutations in Swedish patients

Cited by 9 publications

References 21 publications

Malignant hyperthermia: a review

Malignant hyperthermia: a review

Male preponderance of patients testing positive for malignant hyperthermia susceptibility

Clinical and Pathologic Findings of Korean Patients with RYR1-Related Congenital Myopathy

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