Natural History Studies on the Inherited Neuropathies

夏可玛丽牙病（CMT）是遗传性周围神经病变的代名词。CMT影响约1 / 2500人，可分为三个大的亚组；CMT1（显性遗传性脱髓鞘神经病），CMT2（显性遗传性轴突神经病）和CMT4（隐性遗传性神经病）。CMT1、CMT2和CMT4是由70多个基因突变引起的。这些疾病的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，由于缺乏自然史数据，缺乏对短期变化敏感的结果测量，以及缺乏对患有CMT的幼儿的结果测量，临床试验受到限制。在RDCRN的第一个周期中，我们已经招募了超过4200名患者加入遗传性神经病变联盟（INC）的方案。我们的患者权益组织（PAGs）的支持使我们能够在INC内从6个站点扩展到15个站点。来自NINDS的额外支持使我们能够开发CMT-国际数据库（CMT- id），这是一组国家CMT登记处，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变患者。

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.