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

Participation Requirements

• Sex:

  ALL

• Eligible Ages:

  0 and up

Participation Criteria

Inclusion Criteria:

All patients must be seen in-person at a participating center for the initial visit.

Inclusion Criteria - patients with CMT (all subtypes)

1. Patient has documented, pathogenic or likely pathogenic CMT-causing variant(s)

OR
2. Patient has a first- or second-degree family member (parent, child, sibling, half-sibling, aunt, uncle, grandparent, or grandchild) with a documented pathogenic or likely pathogenic CMT-causing variant AND a clear link between that family member and the affected patient AND a phenotype consistent with the diagnosis

i. A clear link is necessary for a second-degree relative. For example, if a grandparent is affected and has a pathogenic or likely pathogenic variant, and the parent does not have any signs, symptoms, or electrophysiology consistent with the diagnosis, there is no clear link unless the parent has also been found to have the pathogenic or likely pathogenic variant such as in cases with reduced penetrance

ii. 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:

i. Variant is categorized as pathogenic or likely pathogenic per the ACMG variant interpretation guidelines. \[80, 81\]

ii. 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).

iii. The principal investigator and the site investigator agree that the variant(s) is (are) most likely pathogenic.
4. Patients whose clinical presentation is suggestive of CMT, but CMT type and variant are unknown will be characterized by the following categories:

1. Nerve conduction velocities: demyelinating, axonal, intermediate
2. Inheritance: dominant, recessive, X-linked, or unknown
5. Patient or patient's legally authorized representative has understood and signed an IRB approved consent form for the study. Teenagers (age 13 - 17 years) and cognitively impaired adults who are able to read and write 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.