Department of Neuromuscular Diseases, Medical Research Council Centre for Neuromuscular Diseases, University College London Queen Square Institute of Neurology, London, UK; National Hospital for Neurology and Neurosurgery, University College London Hospitals National Health Service Foundation Trust, London, UK.
Department of Clinical and Experimental Epilepsy, University College London Queen Square Institute of Neurology, London, UK; Chalfont Centre for Epilepsy, Buckinghamshire, UK; National Hospital for Neurology and Neurosurgery, University College London Hospitals National Health Service Foundation Trust, London, UK.
Lancet Child Adolesc Health. 2020 Jul;4(7):536-547. doi: 10.1016/S2352-4642(19)30425-0. Epub 2020 Mar 3.
Voltage-gated sodium channels are essential for excitability of skeletal muscle fibres and neurons. An increasing number of disabling or fatal paediatric neurological disorders linked to mutations of voltage-gated sodium channel genes are recognised. Muscle phenotypes include episodic paralysis, myotonia, neonatal hypotonia, respiratory compromise, laryngospasm or stridor, congenital myasthenia, and myopathy. Evidence suggests a possible link between sodium channel dysfunction and sudden infant death. Increasingly recognised phenotypes of brain sodium channelopathies include several epilepsy disorders and complex encephalopathies. Together, these early-onset muscle and brain phenotypes have a substantial morbidity and a considerable mortality. Important advances in understanding the pathophysiological mechanisms underlying these channelopathies have helped to identify effective targeted therapies. The availability of effective treatments underlines the importance of increasing clinical awareness and the need to achieve a precise genetic diagnosis. In this Review, we describe the expanded range of phenotypes of muscle and brain sodium channelopathies and the underlying knowledge regarding mechanisms of sodium channel dysfunction. We also outline a diagnostic approach and review the available treatment options.
电压门控钠离子通道对于骨骼肌纤维和神经元的兴奋性至关重要。越来越多的与电压门控钠离子通道基因突变相关的使人致残或致命的儿科神经疾病被识别。肌肉表型包括发作性瘫痪、肌强直、新生儿低张力、呼吸功能障碍、喉痉挛或喘鸣、先天性肌无力和肌病。有证据表明，钠离子通道功能障碍与婴儿猝死之间可能存在关联。越来越多被识别的脑钠通道病的表型包括几种癫痫疾病和复杂脑病。这些早发型的肌肉和脑表型具有较高的发病率和死亡率。对这些通道病的病理生理机制的理解的重要进展有助于确定有效的靶向治疗。有效的治疗方法的出现强调了提高临床认识的重要性，以及需要进行精确的基因诊断。在这篇综述中，我们描述了肌肉和脑钠通道病的扩展表型范围，以及关于钠离子通道功能障碍机制的相关知识。我们还概述了一种诊断方法，并回顾了现有的治疗选择。
