INC: Pediatric Study of Charcot-Marie-Tooth Disease

Brief Summary

The Inherited Neuropathies Consortium (INC) is an integrated group of medical centers that conducts clinical research in different forms of Charcot-Marie-Tooth Disease (CMT). Funded by the National Institutes of Health, the INC is part of the Rare Diseases Clinical Research Network. 

Using cohort data, INC scientists conduct projects to:

• Study how certain forms of CMT change over time
• Understand genetic modifiers to CMT1A
• Identify new genetic causes for axonal forms of CMT
• Standardize CMT scoring systems for the pediatric population

Although each INC center is expert in the evaluation and management of patients with CMT, the goal of the INC is not to provide care but to conduct research. However, physicians may refer patients for both clinical evaluation and potential research participation.

Primary:

• Determine the natural history and genotype-phenotype correlations of disease-causing mutations in CMT1B, CMT2A, CMT4A, CMT4C, and other forms of CMT

Secondary:

• 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 10-year window

Eligibility Criteria

Inclusion criteria include:
Patients with Charcot-Marie-Tooth disease type 1B (CMT1B) and type 2A (CMT2A) who have:

•  A disease-causing mutation in the MPZ gene (for CMT1B) or in MFN2 (for CMT2A) or
• A first- or second-degree family member with a:
  • Documented disease-causing mutation
  • Clear link between that family member and the affected patient
  • Phenotype consistent with the diagnosis
• A disease-causing variant of uncertain significance
• A variant of uncertain significance that has been found in multiple affected family members and that has not been found in unaffected family members

Patients with Charcot-Marie-Tooth disease type 4A (CMT4A) and 4C (CMT4C) must have one of the following:

• Two documented, disease-causing mutations in the GDAP1 gene (for CMT4A) or 2 mutations in the SH3TC2 gene (for CMT4C)
• Patient with variants of uncertain significance has 1 known disease-causing mutation and one known disease-causing variant
• Patient with variants of uncertain significance has 2 variants that are disease-causing mutations
• Patient with variants of uncertain significance is homozygous for a variant with or without parent

Study Sites

St. Jude Children’s Research Hospital and other centers in the U.S.

About This Study

This long-term research study will help scientists learn more about Charcot-Marie-Tooth disease (CMT). CMT is a hereditary disorder that affects the nerves.

This study takes place in many locations, and some of those treat adults. St. Jude focuses on children and young adults. If you enroll in the INC study, you will visit St. Jude once a year for physical exams and to answer questions. Scientists will measure changes in your strength, sensation, and how well the nerves going to the hands and feet conduct a signal over many years. You may also donate blood or skin samples for research testing if you choose.

St. Jude also invites family members who are not affected with CMT but are at the clinic to take part in certain aspects of this study.

Purpose of This Clinical Trial

This long-term study aims to better understand the genetic causes of Charcot-Marie-Tooth disease (CMT) and to learn how different forms of the rare hereditary disease affect people over time.

Eligibility Overview

• Patients with Charcot-Marie-Tooth disease
• Birth to 22 years