RYR1相关肌病是最常见的先天性肌病，但长期自然病史数据仍然较为匮乏。我们的目的是描述显性和隐性RYR1相关肌病的自然病史。通过对1992年至2019年期间在两个英国大型中心接受治疗的RYR1相关肌病儿童病例进行横断面和纵向回顾性数据分析。患者通过个人病历进行识别和数据收集。共有69名患者纳入研究，其中63名患者同时参与了横断面和纵向研究，6名患者仅参与了横断面分析。发病时间从出生到7岁不等。29名患者患有常染色体显性RYR1相关肌病，31名为隐性，6名为新生显性，3名遗传方式不确定。首次和最后就诊的中位年龄分别为4.0岁和10.8岁。超过2岁的患者中，有15%从未行走过（其中包括5名隐性、4名新生显性和1名显性患者），7%在随访期间丧失了行走能力。脊柱侧弯和脊柱僵硬分别在30%和17%的患者中存在。22%的患者存在呼吸系统受累，12%从7岁的中位年龄开始需要呼吸支持。30%的患者存在进食困难，其中57%需要胃造瘘或管饲。在这个研究中没有报道麻醉相关的恶性高热症发作。我们观察到在隐性患者中出生前/新生儿特征的患病率较高，尤其是低张力和呼吸困难。临床表现、呼吸和进食结果在隐性组中一直较为严重。相反，纵向分析表明隐性患者的运动和呼吸功能病程较为不进展。隐性患者的每年强迫 vitals 容量变化为-0.2%/年，而显性患者为-1.4%/年。本临床研究提供了RYR1相关肌病疾病进展的长期数据，有助于指导治疗并为未来的治疗干预提供重要的里程碑。©2023美国神经学会。

RYR1-related myopathies are the most common congenital myopathies, but long term natural history data is still scarce. We aim to describe the natural history of dominant and recessive RYR1-related myopathies.Cross-sectional and longitudinal retrospective data analysis of pediatric cases with RYR1-related myopathies seen between 1992-2019 in two large UK centres. Patients were identified and data collected from individual medical records.69 patients were included in the study, 63 in both cross-sectional and longitudinal studies, and 6 in the cross-sectional analysis only. Onset ranged from birth to 7 years. Twenty-nine patients had an autosomal dominant RYR1-related myopathy, 31 recessive, 6 de novo dominant and 3 uncertain inheritance. Median age at first and last appointment was 4.0 and 10.8 years, respectively. Fifteen% of patients older than 2 years never walked (5 recessive, 4 de novo dominant and 1 dominant patient) and 7% lost ambulation during follow up. Scoliosis and spinal rigidity were present in 30% and 17% of patients, respectively. Respiratory involvement was observed in 22% of patients, and 12% needed ventilatory support from a median age of 7 years. Feeding difficulties were present in 30% of patients and 57% of those needed gastrostomy or tube feeding. There were no anaesthetic-induced malignant hyperthermia episodes reported in this cohort. We observed a higher prevalence of prenatal/neonatal features in recessive patients, in particular hypotonia and respiratory difficulties. Clinical presentation, respiratory and feeding outcomes were consistently more severe at presentation and in the recessive group. Conversely, longitudinal analysis suggested a less progressive course for motor and respiratory function in recessive patients. Annual change in forced vital capacity was -0.2%/year in recessive vs -1.4%/year in dominant patients.This clinical study provides long-term data on disease progression in RYR1-related myopathies that may inform management and provide essential milestones for future therapeutic interventions.© 2023 American Academy of Neurology.