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

Inclusion Criteria

General Criteria

1\. All patients must agree to take part in the study and sign a consent form. Teenagers (age 13-17 years) must sign an assent form (depending on local ethics committee requirements).

Patients:

1. Must have a documented, disease-causing variant(s) in a gene with a known or preliminary association with CMT gene as per Strande et al. 2017 AND consistent with the inheritance pattern associated with the genetic subtype (heterozygous in autosomal dominant, biallelic in autosomal recessive, hemizygous males with X-linked).
2. OR have a first- or second-degree family member (parent, child, sibling, half-sibling, aunt, uncle, grandparent, or grandchild) with a documented disease-causing variant(s) as above AND a clear link between that family member and the affected patient AND a phenotype consistent with the diagnosis.
3. In cases where clear links are not available, genetic confirmation is required.
4. Patients who have a variant(s) of uncertain significance on clinical laboratory reports may still be included if:
5. The variant is categorized as pathogenic or likely pathogenic per the "Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology." (Richards et al., 2015)
6. OR the variant has been found in multiple affected people in a family and has not been found in unaffected family members per "ClinGen guidance for use of the PP1/BS4 co-segregation and PP4 phenotype specificity criteria for sequence variant pathogenicity classification." (Biesecker et al. 2023)
7. OR the principal investigator and the site investigator agree that the variant(s) is (are) likely disease-causing.

Controls

1. Must not have a peripheral neuropathy, as determined by the site investigator.
2. Must have 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

Patients:

1. Patient does not wish to participate or does not sign a consent form.
2. Patient has a different potential cause for their neuropathy AND no disease-causing variant(s).
3. Deemed inappropriate by the Site PI.