Atypical periodic paralysis and myalgia: A novel RYR1 phenotype.
Atypical periodic paralysis and myalgia: A novel RYR1 phenotype.
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DOI：
10.1212/wnl.0000000000004894
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发表时间：
2018-01-30
期刊：
影响因子：
9.9
通讯作者：
Hanna MG
中科院分区：
文献类型：
--
作者：
Matthews E;Neuwirth C;Jaffer F;Scalco RS;Fialho D;Parton M;Raja Rayan D;Suetterlin K;Sud R;Spiegel R;Mein R;Houlden H;Schaefer A;Healy E;Palace J;Quinlivan R;Treves S;Holton JL;Jungbluth H;Hanna MG
目的研究周期性麻痹(PP)和兰尼定受体(RYR1)基因突变患者的表型特征。可能被诊断为PP，但有其他临床病理结果与RYR1相关疾病相关的病例被转至第三级神经肌肉临床评估，在该临床评估中，他们接受了详细的临床评估，包括神经生理学评估、肌肉活检和肌肉MRI。用下一代测序和/或靶向Sanger测序进行遗传分析。三个发作性肌肉麻痹或虚弱的病例以及与RYR1相关的肌病相关的其他发现被确认。用于诊断PP的McManis试验3例中2例阳性。已知PP基因的遗传分析为阴性。RyR1分析在所有3例病例中都证实了可能的致病变异。RyR1突变可导致晚发性非典型PP，并伴有或不伴有相关的肌病。肌肉酸痛和抽筋是其显著特征。McManis试验可能是诊断RYR1相关PP的有用工具。我们建议，在基因未明确的PP病例中，应寻找RYR1相关疾病的临床病理特征，而在SCN4A、CACNA1S和KCNJ2突变已被排除的病例中，应考虑进行RYR1基因检测。
To characterize the phenotype of patients with symptoms of periodic paralysis (PP) and ryanodine receptor (RYR1) gene mutations. Cases with a possible diagnosis of PP but additional clinicopathologic findings previously associated with RYR1-related disorders were referred for a tertiary neuromuscular clinical assessment in which they underwent detailed clinical evaluation, including neurophysiologic assessment, muscle biopsy, and muscle MRI. Genetic analysis with next-generation sequencing and/or targeted Sanger sequencing was performed. Three cases with episodic muscle paralysis or weakness and additional findings compatible with a RYR1-related myopathy were identified. The McManis test, used in the diagnosis of PP, was positive in 2 of 3 cases. Genetic analysis of known PP genes was negative. RYR1 analysis confirmed likely pathogenic variants in all 3 cases. RYR1 mutations can cause late-onset atypical PP both with and without associated myopathy. Myalgia and cramps are prominent features. The McManis test may be a useful diagnostic tool to indicate RYR1-associated PP. We propose that clinicopathologic features suggestive of RYR1-related disorders should be sought in genetically undefined PP cases and that RYR1 gene testing be considered in those in whom mutations in SCN4A, CACNA1S, and KCNJ2 have already been excluded.