シャルコー・マリー・トゥース病—疾患概念の確立と現況

Charcot-Marie-Tooth Disease: Historical Evolution and Present Understanding

シャルコー・マリー・トゥース病は遺伝性運動感覚性ニューロパチーであり，筋力低下や感覚障害を主徴とする。本論ではシャルコー，マリー，トゥースによる原典を基に，本疾患がいかにして疾患概念として確立されたかを述べた。さらに，その後の分類や遺伝子研究の進展，最新の診断・治療の現況を概説し，今後の課題と展望を述べた。

Abstract

Charcot-Marie-Tooth disease is a hereditary motor and sensory neuropathy characterized by progressive distal muscle weakness, atrophy, and sensory impairment. In this article, we review the original reports published in 1886 by Charcot, Marie, and Tooth, analyzing the clinical features they used to distinguish Charcot-Marie-Tooth disease from other forms of muscle atrophy. We then trace the historical development of the disease concept and examine evolving classification systems based on clinical, electrophysiological, and genetic findings. The identification of more than 140 causative genes has complicated traditional classifications based on nerve conduction studies and inheritance patterns. Thus, we also provide an overview of the current diagnostic strategies that combine clinical evaluation with genetic testing. Although no curative treatment is currently available, advances in molecular biology have introduced new avenues for pharmacological and gene-based interventions. Accordingly, we present emerging therapeutic approaches, including siRNA and CRISPR-Cas9 targeting PMP22 for CMT1A, as well as other nucleic acid-based drugs under development.