Natural History Evaluation of Charcot Marie Tooth Disease (CMT) Types CMT1B, CMT2A, CMT4A, CMT4C, and Others (INC-6601)

Patients who present to a participating site and have Charcot Marie Tooth disease (CMT) will be recruited for participation.

Inclusion Criteria:

All patients MUST be seen in person at a participating clinical site to be enrolled in the study.

Inclusion Criteria - Charcot Marie Tooth disease type 1B (CMT1B) and type 2A (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

   • 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.
   • 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:

   • Variant is listed as disease causing at http://www.molgen.ua.ac.be/CMTMutations/Mutations/Default.cfm.
   • 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. See Appendix A for a sample consent form with HIPAA. See Appendix B for a sample assent form.

Inclusion Criteria - Charcot Marie Tooth disease type 4A (CMT4A) and 4C (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:

   • Patient has one known disease causing mutation and one variant that is listed as disease causing at http://www.molgen.ua.ac.be/CMTMutations/Mutations/Default.cfm.

   OR

   • Patient has two variants listed as disease causing mutations at the above website.

   OR

   • Patient is homozygous for a variant with or without consanguineous parents. OR
   • 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.

ADDITIONAL PARTICIPANTS

For patients with other forms of CMT than listed above, we will perform all assessments to prepare for further studies into the disease and the disease process. These patients will be characterized based on their type of CMT, if known, or by the following categories:

• Nerve conduction velocities: demyelinating , axonal, intermediate
• Inheritance: dominant, recessive, X-linked, or unknown

Exclusion Criteria:

1. Patient does not have a documented mutation in MPZ (for CMT1B) or MFN2 (for CMT2A), nor does a first or second degree family member. Patient does not have two documented mutations in GDAP1 (for CMT4A) or SH3TC2 (CMT4C).
2. Patient has a variant of uncertain significance that cannot be further classified following methods listed in the Inclusion Criteria.
3. Patient does not wish to be a part of the study or has not signed an informed consent form.
4. Patient is deemed inappropriate by the Site PI.