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.
TO THE INC RDCRC Developing outcome instruments that measure disease progression in a manner that is relevant to people afflicted with inherited peripheral neuropathies is one of the main goals of the Inherited Neuropathy Consortium (INC). Because these disorders are rare these studies can only be performed in a consortium of trained expert clinical investigators such as those in the INC.
| Jerath, Nivedita U; Mankodi, Ami; Crawford, Thomas O et al. (2018) Charcot-Marie-Tooth Disease type 4C: Novel mutations, clinical presentations, and diagnostic challenges. Muscle Nerve 57:749-755 |
| Tomaselli, Pedro J; Horga, Alejandro; Rossor, Alexander M et al. (2018) IGHMBP2 mutation associated with organ-specific autonomic dysfunction. Neuromuscul Disord 28:1012-1015 |
| Johnson, Nicholas E; Heatwole, Chad; Creigh, Peter et al. (2018) The Charcot-Marie-Tooth Health Index: Evaluation of a Patient-Reported Outcome. Ann Neurol 84:225-233 |
| Davies, Jenny L; Engelstad Sr.,, Janean K; E Gove, Linde et al. (2018) Somatotopic heat pain thresholds and intraepidermal nerve fibers in health. Muscle Nerve 58:509-516 |
| Saghira, Cima; Bis, Dana M; Stanek, David et al. (2018) Variant pathogenicity evaluation in the community-driven Inherited Neuropathy Variant Browser. Hum Mutat 39:635-642 |
| Shy, Michael; Rebelo, Adriana P; Feely, Shawna Me et al. (2018) Mutations in BAG3 cause adult-onset Charcot-Marie-Tooth disease. J Neurol Neurosurg Psychiatry 89:313-315 |
| Laurá, Matilde; Singh, Dishan; Ramdharry, Gita et al. (2018) Prevalence and orthopedic management of foot and ankle deformities in Charcot-Marie-Tooth disease. Muscle Nerve 57:255-259 |
| Hu, Bo; McCollum, Megan; Ravi, Vignesh et al. (2018) Myelin abnormality in Charcot-Marie-Tooth type 4J recapitulates features of acquired demyelination. Ann Neurol 83:756-770 |
| Dankwa, Lois; Richardson, Jessica; Motley, William W et al. (2018) A mutation in the heptad repeat 2 domain of MFN2 in a large CMT2A family. J Peripher Nerv Syst 23:36-39 |
| Bai, Yunhong; Wu, Xingyao; Brennan, Kathryn M et al. (2018) Myelin protein zero mutations and the unfolded protein response in Charcot Marie Tooth disease type 1B. Ann Clin Transl Neurol 5:445-455 |
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