Status:

RECRUITING

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

Lead Sponsor:

Michael Shy

Collaborating Sponsors:

Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta

Johns Hopkins University

Conditions:

Charcot Marie Tooth Disease

Eligibility:

All Genders

Brief Summary

This is an observational longitudinal study to determine the natural history and genotype-phenotype correlations of disease causing mutations in Charcot Marie Tooth disease (CMT) type 1B (CMT1B), 2A (...

Detailed Description

The Inherited Neuropathies Consortium (INC) is a member of the Rare Disease Clinical Research Network (RDCRN) that is funded by the National Institutes of Health (NIH) through the Office of Rare Disea...

Eligibility Criteria

Inclusion

  • Inclusion Criteria:
  • All patients must be seen in-person at a participating center for the initial visit.
  • Inclusion Criteria - patients with CMT (all subtypes)
  • Patient has documented, pathogenic or likely pathogenic CMT-causing variant(s)
  • OR
  • 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.
  • 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.
  • Patients whose clinical presentation is suggestive of CMT, but CMT type and variant are unknown will be characterized by the following categories:
  • Nerve conduction velocities: demyelinating, axonal, intermediate
  • Inheritance: dominant, recessive, X-linked, or unknown
  • 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
  • Person does not have a peripheral neuropathy, as determined by the investigator.
  • 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
  • Patient has a variant of uncertain significance that cannot be further classified following methods listed in the Inclusion Criteria.
  • Patient does not wish to be a part of the study or has not signed an informed consent form.
  • Patient is deemed inappropriate by the Site PI.

Exclusion

    Key Trial Info

    Start Date :

    April 1 2010

    Trial Type :

    OBSERVATIONAL

    Allocation :

    ESTIMATED

    End Date :

    December 1 2026

    Estimated Enrollment :

    5000 Patients enrolled

    Trial Details

    Trial ID

    NCT01193075

    Start Date

    April 1 2010

    End Date

    December 1 2026

    Last Update

    October 7 2025

    Active Locations (22)

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    Page 1 of 6 (22 locations)

    1

    Cedars-Sinai Medical Center

    Los Angeles, California, United States, 90048

    2

    Stanford University

    Palo Alto, California, United States, 94305

    3

    University of Colorado Hospital

    Aurora, Colorado, United States, 80045

    4

    University of Connecticut/Connecticut Children's Medical Center

    Hartford, Connecticut, United States, 06106