Berciano J, Sevilla T, Casasnovas C, Sivera R, Vílchez J J, Infante J, Ramón C, Pelayo-Negro A L, Illa I
Servicio de Neurología, Hospital Universitario Marqués de Valdecilla (IFIMAV), Universidad de Cantabria, CIBERNED, Santander, España.
Neurologia. 2012 Apr;27(3):169-78. doi: 10.1016/j.nrl.2011.04.015. Epub 2011 Jun 23.
Charcot-Marie-Tooth disease (CMT) is the most frequent form of inherited neuropathy. In accordance with the inheritance pattern and degree of slowing of motor conduction velocity (MCV) of the median nerve, CMT encompasses five main forms: CMT1 (autosomal dominant [AD] or X-linked transmission and MCV < 38 m/s); CMT2 (AD or X-linked transmission and MCV > 38 m/s); CMT4 (autosomal recessive [AR] and severe slowing of MCV); AR-CMT2 (AR transmission and MCV > 38 m/s); and DI-CMT (intermediate form with AD transmission and MCV between 30 and 40 m/s). In spite of its stereotyped semiological repertoire (basically, symptoms and signs of sensory-motor polyneuropathy and pes cavus), CMT seems to be one of the most complex hereditary neurodegenerative syndromes, 31 causative genes having been cloned.
This paper is aimed at performing a nosological review of the disease, emphasising the guidelines for its molecular diagnosis. Genetic epidemiological studies and genotypes reported in Spanish patients are revised.
In the great majority of CMT cases, mutations involve a reduced number of genes, namely: for CMT1, PMP22, GJB1 and MPZ; for CMT2, MFN2 and GJB1; for CMT4, GDAP1, and NDRG1, HK1 and SH3TC2 (gypsies); for AR-CMT2, GDAP1; and for DI-CMT, GJB1 and MPZ. Given their low prevalence, mutations in other pathogenic genes should be investigated after discarding the previous ones. There is no place for the indiscriminate use of diagnostic CMT genetic panels.
夏科-马里-图斯病（CMT）是遗传性神经病最常见的形式。根据正中神经运动传导速度（MCV）减慢的遗传模式和程度，CMT主要包括五种类型：CMT1（常染色体显性遗传[AD]或X连锁遗传，MCV<38 m/s）；CMT2（AD或X连锁遗传，MCV>38 m/s）；CMT4（常染色体隐性遗传[AR]，MCV严重减慢）；AR-CMT2（AR遗传，MCV>38 m/s）；以及DI-CMT（AD遗传的中间型，MCV在30至40 m/s之间）。尽管CMT有其固定的症状表现（基本上是感觉运动性多神经病和高弓足的症状和体征），但它似乎是最复杂的遗传性神经退行性综合征之一，目前已克隆出31个致病基因。
本文旨在对该疾病进行分类学综述，重点强调其分子诊断指南。对西班牙患者的遗传流行病学研究和报告的基因型进行了修订。
在绝大多数CMT病例中，突变涉及的基因数量较少，即：对于CMT1，为PMP22、GJB1和MPZ；对于CMT2，为MFN2和GJB1；对于CMT4，为GDAP1、NDRG1、HK1和SH3TC2（吉普赛人）；对于AR-CMT2，为GDAP1；对于DI-CMT，为GJB1和MPZ。鉴于其他致病基因的患病率较低，在排除上述基因后应研究其突变情况。诊断CMT的基因检测不应随意使用。
