English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

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.

Ryanodine receptor 1-related disorders: an historical perspective and proposal for a unified nomenclature