Abstract：
Brody disease is a rare autosomal recessive myopathy, caused by pathogenic variants in the ATP2A1 gene. It is characterized by an exercise-induced delay in muscle relaxation, often reported as muscle stiffness. Children may manifest with an abnormal gait and difficulty running. Delayed relaxation is commonly undetected, resulting in a long diagnostic delay. Almost all published cases so far were adults with childhood onset and adult diagnosis. With diagnostic next-generation sequencing, an increasing number of patients are diagnosed in childhood. We describe the clinical and genetic features of 9 children from 6 families with Brody disease. All presented with exercise-induced delayed relaxation, reported as difficulty running and performing sports. Muscle strength and mass was normal, and several children even had an athletic appearance. However, the walking and running patterns were abnormal. The diagnostic delay ranged between 2 and 7 years. Uniformly, a wide range of other disorders were considered before genetic testing was performed, revealing pathogenic genetic variants in ATP2A1. To conclude, this case series is expected to improve clinical recognition and timely diagnosis of Brody disease in children. We propose that ATP2A1 should be added to gene panels for congenital myopathies, developmental and movement disorders, and muscle channelopathies.
摘要：
Brody病是一种罕见的常染色体隐性肌病,由ATP2A1基因的致病变异引起。它的特点是运动引起的肌肉放松延迟，经常报告为肌肉僵硬。儿童可能表现为步态异常和跑步困难。延迟松弛通常是未被发现的，导致长时间的诊断延迟。到目前为止，几乎所有已发表的病例都是儿童发病和成人诊断的成年人。有了诊断下一代测序，越来越多的患者在儿童时期被诊断。我们描述了来自6个Brody病家庭的9名儿童的临床和遗传特征。都表现为运动引起的延迟放松，报告为跑步和表演运动困难。肌肉力量和质量正常，几个孩子甚至有运动的外表。然而,步行和跑步模式异常。诊断延迟在2至7年之间。均匀,在进行基因检测之前，还考虑了各种各样的其他疾病，揭示ATP2A1的致病性遗传变异。最后，该病例系列有望提高临床对儿童Brody病的认识和及时诊断。我们建议将ATP2A1添加到先天性肌病的基因面板中，发育和运动障碍，和肌肉信道病。
