Natural History Studies on the Inherited Neuropathies

Charcot Marie Tooth(CMT)是遗传性周围神经病的代名词。CMT影响大约2500人中的1人，并可分为三大亚组：CMT1(显性遗传性脱髓鞘神经病)、CMT2(显性遗传性轴索神经病)和CMT4(隐性遗传性神经病)。70多个基因的突变导致CMT1、CMT2和CMT4。这些疾病中脱髓鞘和轴突变性的生物学基础使某些类型的CMT的合理治疗发展成为可能。然而，由于缺乏自然病史数据，缺乏对短期变化敏感的结果指标，以及缺乏针对患有CMT的幼儿的结果指标，临床试验一直受到限制。在RDCRN的第一个周期中，我们已经招募了4200多名患者加入遗传性神经病联盟(INC)的方案。在我们患者权益倡导团体(PAG)的支持下，我们已将Inc.内的6个站点扩展到15个站点。NINDS的额外支持使我们得以开发CMT-国际数据库(CMT-ID)，这是一组国家CMT注册机构，他们也使用CMT最小数据集，并将其数据存放在DMCC。综上所述，我们有一个独特的机会来获得和评估罕见形式的遗传性神经病患者。 我们建议在未来五年内延长我们的工作，具体目标如下： 目的1：拓展CMT1A型、CMT1B型、CMT1X型和CMT2A型的自然历史研究。 目的2：收集和评估罕见类型的CMT患者。 目的3：验证和测试成人CMT患者报告的残疾和生活质量量表。 目的4：验证CMT患儿的婴幼儿残疾和生活质量量表。

Charcot Marie Tooth disease (CMT) is the eponym for heritable peripheral neuropathy. CMT affects approximately 1 in 2500 people and is divisible into three large sub-groups; CMT1 (dominantly inherited demyelinating neuropathies), CMT2 (dominantly inherited axonal neuropathies), and CMT4 (recessively inherited neuropathies). Mutations in more than 70 genes cause CMT1, CMT2 and CMT4. The biological basis for demyelination and axonal degeneration in these disorders has enabled rational therapy development for some kinds of CMT. Clinical trials, however, have been limited by a combination of a lack of natural history data, a lack of outcome measures that are sensitive to change in a short period, and a lack of outcome measures for young children with CMT. We have enrolled over 4200 patients into the protocols of the Inherited Neuropathy Consortium (INC) during our first cycle in the RDCRN. Support from our patient advocacy groups (PAGs) has allowed us to expand from 6 to 15 sites within the INC. Additional support from NINDS allowed us to develop the CMT-lnternational Database (CMT-ID), a group of national CMT registries who also use the CMT Minimal Dataset and house their data at the DMCC. Taking these together, we have a unique opportunity to obtain and evaluate patients with rare forms of inherited neuropathy. We propose to extend our work over the next 5 years with the following Specific Aims: Aim 1: Expand natural history investigations on CMT1A, CMT1B, CMT1X and CMT2A. Aim 2: Accrue and evaluate patients with rare forms of CMT. Aim 3: Validate and test patient reported disability and QOL instruments in adults with CMT. Aim 4: Validate infant-toddler disability and QOL instruments in children with CMT.