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.

中文翻译：

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Ryanodine 受体 1 相关疾病：统一命名的历史观点和建议

RYR1 基因编码肌浆网钙释放通道或骨骼肌的 1 型兰尼碱受体 (RyR1)，于 1988 年进行测序，1991 年首次发现损害钙稳态和增加对恶性高热易感性的 RYR1 变异。从那时起， RYR1 相关肌病 (RYR1-RM) 已被描述为罕见、组织病理学和临床异质性、进展缓慢的神经肌肉疾病。RYR1 变体可导致功能失调的 RyR1 介导的钙释放、恶性高热易感性、氧化应激升高、有害的翻译后修饰和 RyR1 表达降低。受 RYR1-RM 影响的个体可能出现运动里程碑延迟、挛缩、脊柱侧弯、眼肌麻痹和呼吸功能不全。从历史上看，受 RYR1-RM 影响的个体根据在肌肉活检中观察到的形态学特征进行诊断，包括中央核、核心和棒、中央核、纤维类型不对称和多微核。然而，这些组织病理学特征并不总是特定于 RYR1-RM，并且经常随着时间而改变。由于其他表型与 RYR1 变异相关（包括 King-Denborough 综合征、运动诱发的横纹肌溶解症、致死性多发性翼状胬肉综合征、成人发病的远端肌病、伴有或不伴有肌痛的非典型周期性麻痹、轻度小腿为主的肌病和灰质核心病）诊断类别之间的重叠不断增加。随着 RYR1 疾病谱中新临床亚型的不断出现和成人发病表型的报告，已经报道了细微的命名法（RYR1- [相关，相关的先天性，先天性]肌病）。在这篇叙述性综述中，我们提供了 RYR1 研究的历史亮点、主要诊断疾病亚型的说明，并提出了 RYR1 相关疾病 (RYR1-RD) 作为描述这种复杂且不断演变的疾病谱的统一命名法。