Are Myotonias and Periodic Paralyses Associated With Susceptibility to Malignant Hyperthermia?

Lehmann‐Horn, Frank; Iaizzo, Paul A.

doi:10.1093/bja/65.5.692

Cited by 87 publications

(37 citation statements)

References 28 publications

(46 reference statements)

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“…Interestingly, mutations linked to hypokalemic periodic paralysis have been reported in the same gene, 71,133 although the disorder is not thought to be associated to MH susceptibility. 87 For the MHS-6 locus, no causative gene has been identified to date.…”

Section: Secondary Locimentioning

confidence: 99%

“…It seems very likely that the molecular mechanisms underlying these MH-like events differ from those of true MH susceptibility, i.e., increased sensitivity of skeletal muscle to the triggering agents by an increased resting calcium level 158 or increased myotonic reactions to anesthetic agents. 87 This, of course, does not obviate the need for caution when considering general anesthesia in these disorders.…”

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confidence: 99%

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Genetics and pathogenesis of malignant hyperthermia

2000

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Malignant hyperthermia (MH) is a potentially life-threatening event in response to anesthetic triggering agents, with symptoms of sustained uncontrolled skeletal muscle calcium homeostasis resulting in organ and systemic failure. Susceptibility to MH, an autosomal dominant trait, may be associated with congenital myopathies, but in the majority of the cases, no clinical signs of disease are visible outside of anesthesia. For diagnosis, a functional test on skeletal muscle biopsy, the in vitro contracture test (IVCT), is performed. Over 50% of the families show linkage of the IVCT phenotype to the gene encoding the skeletal muscle ryanodine receptor and over 20 mutations therein have been described. At least five other loci have been defined implicating greater genetic heterogeneity than previously assumed, but so far only one further gene encoding the main subunit of the voltage-gated dihydropyridine receptor has a confirmed role in MH. As a result of extensive research on the mechanisms of excitation-contraction coupling and recent functional characterization of several disease-causing mutations in heterologous expression systems, much is known today about the molecular etiology of MH.

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Section: Secondary Locimentioning

confidence: 99%

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confidence: 99%

Genetics and pathogenesis of malignant hyperthermia

2000

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“…The question of the association of hypoPP and malignant hyperthermia arose from the difficulty of interpreting unambiguously in vitro contracture tests in muscle disorders caused by ion channel mutations. 71 We now know that malignant hyperthermia and hypoPP are different diseases caused by distinct mutations in the same gene; the voltage-gated calcium channel CACNA1S. 72,73 Some precautions should be taken during anesthetic procedures in hypoPP patients: intravenous glucose should be avoided and the temperature of fluids and their ionic composition should be carefully monitored.…”

Section: Treatment and Care Of Hypopp Patientsmentioning

confidence: 99%

Hypokalemic Periodic Paralysis: A Model for a Clinical and Research Approach to a Rare Disorder

et al. 2007

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Summary:Rare diseases have attracted little attention in the past from physicians and researchers. The situation has recently changed for several reasons. First, patient associations have successfully advocated their cause to institutions and governments. They were able to argue that, taken together, rare diseases affect approximately 10% of the population in developed countries. Second, almost 80% of rare diseases are of genetic origin. Advances in genetics have enabled the identification of the causative genes. Unprecedented financial support has been dedicated to research on rare diseases, as well as to the development of referral centers aimed at improving the quality of care. This expenditure of resources is justified by the experience in cystic fibrosis, which demonstrated that improved care delivered by specialized referral centers resulted in a dramatic increase of life expectancy. Moreover, clinical referral centers offer the unique possibility of developing high quality clinical research studies, not otherwise possible because of the geographic dispersion of patients. This is the case in France where national referral centers for rare diseases were created, including one for muscle channelopathies. The aim of this center is to develop appropriate care, clinical research, and teaching on periodic paralysis and myotonia. In this review, we plan to demonstrate how research has improved our knowledge of hypokalemic periodic paralysis and the way we evaluate, advise, and treat patients. We also advocate for the establishment of international collaborations, which are mandatory for the follow-up of cohorts and conduct of definitive therapeutic trials in rare diseases.

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“…The mutation is located in an intracellular loop of the protein, whose functional significance for EC coupling is under debate (57). Although mutations in the same gene cause hypokalemic PP type 1, this disorder is not thought to be associated with MH susceptibility (58,59).…”

Section: Figurementioning

confidence: 99%

“…Apparently some of the families had a muscle Na + channelopathy (98,99), which could explain the anesthesia-related events as exaggerated myotonic reactions. The generalized muscle spasms and resulting systemic alterations are usually triggered by succinylcholine in patients with a Na + channelopathy and can resemble MH; as further evidence for the myotonic origin of the crises, susceptibility to MH was excluded in such patients by the European in vitro contracture test (32,58,(100)(101)(102). Suggestions of 4 further MH loci, made each in a single pedigree, still await confirmation.…”

Section: Genetic Linkage Studies Within Familiesmentioning

confidence: 99%

Muscle channelopathies and critical points in functional and genetic studies

Jurkat‐Rott

Lehmann‐Horn²

2005

Journal of Clinical Investigation

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Muscle channelopathies are caused by mutations in ion channel genes, by antibodies directed against ion channel proteins, or by changes of cell homeostasis leading to aberrant splicing of ion channel RNA or to disturbances of modification and localization of channel proteins. As ion channels constitute one of the only protein families that allow functional examination on the molecular level, expression studies of putative mutations have become standard in confirming that the mutations cause disease. Functional changes may not necessarily prove disease causality of a putative mutation but could be brought about by a polymorphism instead. These problems are addressed, and a more critical evaluation of the underlying genetic data is proposed.

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Are Myotonias and Periodic Paralyses Associated With Susceptibility to Malignant Hyperthermia?

Cited by 87 publications

References 28 publications

Genetics and pathogenesis of malignant hyperthermia

Genetics and pathogenesis of malignant hyperthermia

Hypokalemic Periodic Paralysis: A Model for a Clinical and Research Approach to a Rare Disorder

Muscle channelopathies and critical points in functional and genetic studies

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