Continuum (Minneap Minn). 2020 Oct;26(5):1224-1256. doi: 10.1212/CON.0000000000000927.
This article provides an overview of Charcot-Marie-Tooth disease (CMT) and other inherited neuropathies. These disorders encompass a broad spectrum with variable motor, sensory, autonomic, and other organ system involvement. Considerable overlap exists, both phenotypically and genetically, among these separate categories, all eventually exhibiting axonal injury and neurologic impairment. Depending on the specific neural and non-neural localizations, patients experience varying morbidity and mortality. Neurologic evaluations, including neurophysiologic testing, can help diagnose and predict patient disabilities. Diagnosis is often complex, especially when genetic and acquired components overlap.
Next-generation sequencing has greatly improved genetic diagnosis, with many third-party reimbursement parties now embracing phenotype-based panel evaluations. Through the advent of comprehensive gene panels, symptoms previously labeled as idiopathic or atypical now have a better chance to receive a specific diagnosis. A definitive molecular diagnosis affords patients improved care and counsel. The new classification scheme for inherited neuropathies emphasizes the causal gene names. A specific genetic diagnosis is important as considerable advances are being made in gene-specific therapeutics. Emerging therapeutic approaches include small molecule chaperones, antisense oligonucleotides, RNA interference, and viral gene delivery therapies. New therapies for hereditary transthyretin amyloidosis and Fabry disease are discussed.
Comprehensive genetic testing through a next-generation sequencing approach is simplifying diagnostic algorithms and affords significantly improved decision-making processes in neuropathy care. Genetic diagnosis is essential for pathogenic understanding and for gene therapy development. Gene-targeted therapies have begun entering the clinic. Currently, for most inherited neuropathy categories, specific symptomatic management and family counseling remain the mainstays of therapy.
本文概述了夏科-马里-图思病（CMT）和其他遗传性神经病。这些疾病具有广泛的谱，其特征为运动、感觉、自主神经和其他器官系统受累的多变性。这些独立分类在表型和遗传上都存在相当大的重叠，最终都表现为轴索性损伤和神经功能障碍。根据特定的神经和非神经定位，患者的发病率和死亡率存在差异。神经学评估，包括神经生理学检查，可以帮助诊断和预测患者的残疾。诊断通常很复杂，尤其是遗传和获得性因素重叠时。
下一代测序极大地提高了遗传诊断的能力，许多第三方报销机构现在接受基于表型的小组评估。通过综合基因小组的出现，以前被标记为特发性或非典型的症状现在更有可能得到明确的诊断。明确的分子诊断为患者提供了更好的护理和咨询。遗传性神经病的新分类方案强调了因果基因名称。明确的基因诊断很重要，因为针对特定基因的治疗方法正在取得重大进展。新兴的治疗方法包括小分子伴侣、反义寡核苷酸、RNA 干扰和病毒基因传递疗法。还讨论了遗传性转甲状腺素蛋白淀粉样变性和法布里病的新治疗方法。
通过下一代测序方法进行全面的基因检测正在简化诊断算法，并为神经病治疗提供了显著改进的决策过程。遗传诊断对于发病机制的理解和基因治疗的发展至关重要。基因靶向治疗已开始进入临床。目前，对于大多数遗传性神经病类别，特定的对症治疗和家庭咨询仍然是治疗的主要方法。
