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Study Description

Charcot Marie Tooth disease (CMT) is an umbrella term that covers any inherited peripheral neuropathy. People with CMT have a problem with the nerves that go to the feet and hands that cause muscle and sensation loss, as well as difficulty with balance. There are at least forty genes that, when mutated, cause CMT. The purpose of this study is to look at the natural history of CMT to see how it changes over time. Particular emphasis will be put on studying people with CMT1B, CMT2A, CMT4A, and CMT4C, though all people with CMT are encouraged to participate. Participants are invited back on a yearly basis to determine how the changes are occurring.

Objectives:

  • Determine the natural history and genotype-phenotype correlations of disease-causing mutations in CMT1B, CMT2A, CMT4A and CMT4C as well as other forms of CMT
  • Determine the capability of the newly developed CMTPeds score and the Minimal Dataset to measure impairment and perform longitudinal measurements in patients with multiple forms of CMT over a ten-year window

This is a longitudinal study of individuals with CMT. Study participants will be invited to be re-evaluated every year. Evaluations will consist of neurological histories and examinations, selected nerve conduction studies (NCS) as well as completion of assorted clinical outcome measures including the CMTNS, Minimal Dataset, and Peds CMT Scale. Selected CMT patients and controls will also receive glabrous skin biopsies.

  • Study Weblinks:
  • Study Type:
    • Longitudinal
  • Number of study subjects that have individual-level data available through Authorized Access:
Authorized Access
Publicly Available Data (Public ftp)

Connect to the public download site. The site contains release notes and manifests. The site also contains data dictionaries, variable summaries, documents, and truncated analyses, whenever available.

Study Inclusion/Exclusion Criteria

Inclusion Criteria - CMT1B and CMT2A

  1. Patient has documented, disease causing mutation in the MPZ gene (for CMT1B) or in MFN2 (for CMT2A)
    OR
  2. Patient has a first or second degree family member (parent, child, sibling, half-sibling, aunt, uncle, grandparent, or grandchild) with a documented disease causing mutation AND a clear link between that family member and the affected patient AND a phenotype consistent with the diagnosis
    1. A clear link is necessary for a second-degree relative. For example, if a grandparent is affected and has a disease causing mutation, and the parent does not have any signs, symptoms, or electrophysiology consistent with the diagnosis, there is no clear link.
    2. In cases where clear links are not available, genetic testing is required for the patient or the family member who is not clearly affected.
  3. Patients who have a variant of uncertain significance, as determined by the laboratory performing the testing may still be included if one of the following circumstances applies:
    1. Variant is categorized as disease causing per the ACMG variant interpretation guidelines.
    2. Variant has been found in multiple affected people in a family and has not been found in unaffected family members. (Note - both affected and unaffected family members must be tested in this situation to be included).
  4. Patient has understood and signed an IRB approved consent form for the study. Teenagers (age 13 - 17 years) must sign an assent form (depending on local ethics committee requirements).

Inclusion Criteria - CMT4A and CMT4C

  1. Patient has two documented, disease causing mutations in the GDAP1 gene (for CMT4A) or two mutations in the SH3TC2 gene (for CMT4C)
    OR
  2. Patients who have variants of uncertain significance, as determined by the laboratory performing the testing, may still be included if one of the following circumstances applies:
    1. Patient has one known disease causing mutation and one variant that is listed as disease causing per the ACMG variant interpretation guidelines.
      OR
    2. Patient has two variants listed as disease causing mutations at the above guidelines.
      OR
    3. Patient is homozygous for a variant with or without consanguineous parents.
      OR
    4. The principal investigator and the site investigator agree that the variant(s) is (are) most likely disease causing.
  3. Patient has understood and signed an IRB approved consent form for the study. Teenagers (age 13 - 17 years) must sign an assent form (depending on local ethics committee requirements).

Inclusion Criteria - Controls

  1. Person does not have a peripheral neuropathy, as determined by the investigator.
  2. Person has understood and signed an IRB approved consent form for the study. Teenagers (age 13-17 years) must sign an assent form (depending on local ethics committee requirements).

Exclusion Criteria

  1. Patient has a variant of uncertain significance that cannot be further classified following methods listed in the Inclusion Criteria.
  2. Patient does not wish to be a part of the study or has not signed an informed consent form.
  3. Patient is deemed inappropriate by the Site PI.

Study History

  • Study Activated: March 19, 2010

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Diseases/Traits Related to Study (MeSH terms)
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