Neuromuscular disorders are mostly rare diseases with autosomal dominant, recessive, or X-linked inheritance. Interestingly, among patients carrying the same mutations, a range of phenotypic severity is reported. This phenotypic variability in neuromuscular disorders is still not fully understood. This review will focus on genetic modifiers and will briefly describe metabolic pathways, in which they are involved. Genetic modifiers are variants in the same or other genes that modulate the phenotype. Proteins encoded by genetic modifiers in neuromuscular diseases are taking part in different metabolic processes, most commonly in inflammation, growth and regeneration, endoplasmic reticulum metabolism, and cytoskeletal activities. Recent advances in omics technologies, development of computational algorithms, and establishing large international consortia intensified discovery sped up investigation of genetic modifiers. As more individuals affected by neuromuscular disorders are tested, it is often suggested that classic models of genetic causation cannot explain phenotypic variability. There is a growing interest in their discovery and identifying shared metabolic pathways can contribute to design targeted therapies. We provide an update on variants acting as genetic modifiers in neuromuscular disorders and strategies used for their discovery.

神经肌肉疾病通常是罕见的疾病，具有常染色体显性遗传，隐性遗传或X连锁遗传。有趣的是，在携带相同突变的患者中，报道了一系列表型严重性。神经肌肉疾病的这种表型变异性仍未完全了解。这篇综述将侧重于遗传修饰剂，并将简要描述它们所参与的代谢途径。遗传修饰物是调节表型的相同或其他基因中的变异体。神经肌肉疾病中由遗传修饰剂编码的蛋白质参与不同的代谢过程，最常见的是炎症，生长和再生，内质网代谢和细胞骨架活动。组学技术的最新进展，计算算法的发展，建立大型国际财团加强发现，加快了对基因修饰剂的研究。随着对更多受神经肌肉疾病影响的个体进行测试，通常提示经典的遗传因果模型无法解释表型变异性。人们对它们的发现越来越感兴趣，识别共享的代谢途径可有助于设计靶向治疗。我们提供了有关神经肌肉疾病中作为遗传修饰物的变体的最新动态以及用于发现它们的策略。人们对它们的发现越来越感兴趣，识别共享的代谢途径可有助于设计靶向治疗。我们提供了有关神经肌肉疾病中作为遗传修饰物的变体的最新动态以及用于发现它们的策略。人们对它们的发现越来越感兴趣，确定共享的代谢途径可以有助于设计靶向治疗。我们提供了有关神经肌肉疾病中作为遗传修饰剂的变体的最新动态以及用于发现它们的策略。