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Ryanodine receptor 1-related disorders: an historical perspective and proposal for a unified nomenclature.
Skelet Muscle. 2020 11 16; 10(1):32.SM

Abstract

The RYR1 gene, which encodes the sarcoplasmic reticulum calcium release channel or type 1 ryanodine receptor (RyR1) of skeletal muscle, was sequenced in 1988 and RYR1 variations that impair calcium homeostasis and increase susceptibility to malignant hyperthermia were first identified in 1991. Since then, RYR1-related myopathies (RYR1-RM) have been described as rare, histopathologically and clinically heterogeneous, and slowly progressive neuromuscular disorders. RYR1 variants can lead to dysfunctional RyR1-mediated calcium release, malignant hyperthermia susceptibility, elevated oxidative stress, deleterious post-translational modifications, and decreased RyR1 expression. RYR1-RM-affected individuals can present with delayed motor milestones, contractures, scoliosis, ophthalmoplegia, and respiratory insufficiency.Historically, RYR1-RM-affected individuals were diagnosed based on morphologic features observed in muscle biopsies including central cores, cores and rods, central nuclei, fiber type disproportion, and multi-minicores. However, these histopathologic features are not always specific to RYR1-RM and often change over time. As additional phenotypes were associated with RYR1 variations (including King-Denborough syndrome, exercise-induced rhabdomyolysis, lethal multiple pterygium syndrome, adult-onset distal myopathy, atypical periodic paralysis with or without myalgia, mild calf-predominant myopathy, and dusty core disease) the overlap among diagnostic categories is ever increasing. With the continuing emergence of new clinical subtypes along the RYR1 disease spectrum and reports of adult-onset phenotypes, nuanced nomenclatures have been reported (RYR1- [related, related congenital, congenital] myopathies). In this narrative review, we provide historical highlights of RYR1 research, accounts of the main diagnostic disease subtypes and propose RYR1-related disorders (RYR1-RD) as a unified nomenclature to describe this complex and evolving disease spectrum.

Authors+Show Affiliations

Tissue Injury Branch, National Institute of Nursing Research, National Institutes of Health, Bethesda, MD, USA. Tokunbor.lawal@nih.gov.Tissue Injury Branch, National Institute of Nursing Research, National Institutes of Health, Bethesda, MD, USA.Tissue Injury Branch, National Institute of Nursing Research, National Institutes of Health, Bethesda, MD, USA.Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.Departments of Paediatrics and Molecular Genetics, Hospital for Sick Children and University of Toronto, Toronto, Canada.Molecular Physiology & Biophysics, Baylor College of Medicine, Houston, TX, USA.Tissue Injury Branch, National Institute of Nursing Research, National Institutes of Health, Bethesda, MD, USA.Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, NY, USA.

Pub Type(s)

Journal Article
Review
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural

Language

eng

PubMed ID

33190635

Citation

Lawal, Tokunbor A., et al. "Ryanodine Receptor 1-related Disorders: an Historical Perspective and Proposal for a Unified Nomenclature." Skeletal Muscle, vol. 10, no. 1, 2020, p. 32.
Lawal TA, Todd JJ, Witherspoon JW, et al. Ryanodine receptor 1-related disorders: an historical perspective and proposal for a unified nomenclature. Skelet Muscle. 2020;10(1):32.
Lawal, T. A., Todd, J. J., Witherspoon, J. W., Bönnemann, C. G., Dowling, J. J., Hamilton, S. L., Meilleur, K. G., & Dirksen, R. T. (2020). Ryanodine receptor 1-related disorders: an historical perspective and proposal for a unified nomenclature. Skeletal Muscle, 10(1), 32. https://doi.org/10.1186/s13395-020-00243-4
Lawal TA, et al. Ryanodine Receptor 1-related Disorders: an Historical Perspective and Proposal for a Unified Nomenclature. Skelet Muscle. 2020 11 16;10(1):32. PubMed PMID: 33190635.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ryanodine receptor 1-related disorders: an historical perspective and proposal for a unified nomenclature. AU - Lawal,Tokunbor A, AU - Todd,Joshua J, AU - Witherspoon,Jessica W, AU - Bönnemann,Carsten G, AU - Dowling,James J, AU - Hamilton,Susan L, AU - Meilleur,Katherine G, AU - Dirksen,Robert T, Y1 - 2020/11/16/ PY - 2020/05/05/received PY - 2020/08/18/accepted PY - 2020/11/16/entrez PY - 2020/11/17/pubmed PY - 2020/11/17/medline KW - Clinical neurology KW - History KW - Ion channel defects KW - Myopathy KW - Neuromuscular disease KW - Skeletal muscle SP - 32 EP - 32 JF - Skeletal muscle JO - Skelet Muscle VL - 10 IS - 1 N2 - The RYR1 gene, which encodes the sarcoplasmic reticulum calcium release channel or type 1 ryanodine receptor (RyR1) of skeletal muscle, was sequenced in 1988 and RYR1 variations that impair calcium homeostasis and increase susceptibility to malignant hyperthermia were first identified in 1991. Since then, RYR1-related myopathies (RYR1-RM) have been described as rare, histopathologically and clinically heterogeneous, and slowly progressive neuromuscular disorders. RYR1 variants can lead to dysfunctional RyR1-mediated calcium release, malignant hyperthermia susceptibility, elevated oxidative stress, deleterious post-translational modifications, and decreased RyR1 expression. RYR1-RM-affected individuals can present with delayed motor milestones, contractures, scoliosis, ophthalmoplegia, and respiratory insufficiency.Historically, RYR1-RM-affected individuals were diagnosed based on morphologic features observed in muscle biopsies including central cores, cores and rods, central nuclei, fiber type disproportion, and multi-minicores. However, these histopathologic features are not always specific to RYR1-RM and often change over time. As additional phenotypes were associated with RYR1 variations (including King-Denborough syndrome, exercise-induced rhabdomyolysis, lethal multiple pterygium syndrome, adult-onset distal myopathy, atypical periodic paralysis with or without myalgia, mild calf-predominant myopathy, and dusty core disease) the overlap among diagnostic categories is ever increasing. With the continuing emergence of new clinical subtypes along the RYR1 disease spectrum and reports of adult-onset phenotypes, nuanced nomenclatures have been reported (RYR1- [related, related congenital, congenital] myopathies). In this narrative review, we provide historical highlights of RYR1 research, accounts of the main diagnostic disease subtypes and propose RYR1-related disorders (RYR1-RD) as a unified nomenclature to describe this complex and evolving disease spectrum. SN - 2044-5040 UR - https://www.unboundmedicine.com/medline/citation/33190635/Ryanodine_receptor_1-related_disorders:_an_historical_perspective_and_proposal_for_a_unified_nomenclature L2 - https://skeletalmusclejournal.biomedcentral.com/articles/10.1186/s13395-020-00243-4 DB - PRIME DP - Unbound Medicine ER -