CMTR Research Resources

Charcot-Marie-Tooth and Related Neuropathies Consortium

Introduction

The CMTR consortium seeks to promote basic science and clinical research to understand healthy peripheral nerve function and mechanisms of CMT and related neuropathies, with an end goal of developing novel therapeutics for patients.

The following resources* are intended to support CMTR research:

Disease Background
Diagnosis, Management and Treatment
Research Resources
Career Resources

*The CMTR has discussed but does not endorse the listed validated measures.

Please reach out with additional resources that should be included and ideas for resources that need to be developed. Contact information may be found on the CMTR Board of Directors page.

Disease Background

Charcot Marie Tooth disease (CMT) is the most common genetic neuromuscular disorder and refers to all primary inherited disorders of the peripheral nervous system. CMT causes slowly progressive disability affecting the sensory and motor nerves, and over 130 causative genes have been found so far. There are axonal and demyelinating forms. Inheritance can be autosomal dominant, autosomal recessive or X-linked. CMT is sometimes referred to as Hereditary Sensory and Motor Neuropathy (HSMN). Hereditary motor neuropathy (HMN), hereditary sensory neuropathy (HSN), and hereditary sensory and autonomic neuropathy (HSAN) are closely related disorders characterized by the neuronal populations affected.

Although CMTR members primarily study and treat CMT due to its prevalence, all other hereditary neuropathies and multisystem genetic disorders with neuropathy fall under the umbrella of CMTR. Please reference the diagram below for a complete list of CMTR diseases.

For more background information on CMTR diseases please see the following resources:

Disease Background Resources

Diagnosis, Management and Treatment

In general, hereditary neuropathies are usually diagnosed by neurological exam, nerve conduction studies and genetic testing. Resources to guide genetic testing and gene classification can be found below.

Management recommendations are available through GeneReviews. Search by disease or gene to find tailored management recommendations or browse the CMT Overview page.

hATTR is one of the first CMTR diseases with emerging treatment guidelines. A CMTR taskforce is currently working to establish guidelines for treating neuropathy associated with hATTR which will be posted here upon completion. Guidelines for additional CMTR diseases will be established when treatments become available.

Genetic Testing Resources

Research Resources

The CMTR has discussed but does not endorse the listed validated measures.

National and Regional Inherited Neuropathy Registries

Several patient registries have been established to facilitate natural history studies and clinical trials. Please access them through the links below.

Inherited Neuropathy Registries

Clinical Outcome Measures and Biomarkers

Measures of disease severity are required for clinical trials. Several disability scales have been established to measure disease progression and biomarker identification is ongoing.

Clinical Outcome Assessments

www.ClinicalOutcomeMeasures.org contains scoring algorithms, language translations and training materials for several Clinical Outcome Assessments for infants, children and adults with Charcot-Marie-Tooth disease and related peripheral neuropathies, as well as items from the 1000 Norms Project. Many of these instruments were funded by the Inherited Neuropathies Consortium—all are available to the CMT research community free of charge.

Clinical Outcome Assessments on ClinicalOutcomeMeasures.org include:

- CMT Pediatric Scale (CMTPedS) (ages 3-20 years) a reliable and valid clinical outcome assessment to measure disability in children with CMT. Validation of the CMTPedS is published here.
- CMT Infant Scale (CMTInfS) (ages 0-4 years) is a reliable and valid clinical outcome assessment to measure disability in infants with CMT. Validation of the CMTInfS is published here.
- CMT Functional Outcome Measure (CMT-FOM) (ages 18-75 years) a reliable and valid clinical outcome assessment to measure disability in adults with CMT. Validation of the CMT-FOM is published here.
- CMTNSv2 second version, using Rasch analysis (ages 3-99 years), a simple and efficient tool to measure disability in people with CMT. Validation of the CMTNSv2-R is published here.
- Riboflavin Transporter Deficiency Pediatric Scale (RTDPedS) (ages 3-20) is a reliable and valid clinical outcome assessment to measure disability in children with RTD. Validation of the RTDPedS is published here.
- Pediatric Charcot-Marie-Tooth Disease Quality of Life Outcome Measure (pCMT-QOL Child Version)(ages 8-18) is a reliable, valid, and sensitive measure of health-related QOL for children with CMT. Validation is published here.
- Parent-Proxy Pediatric Charcot-Marie-Tooth Disease Quality of Life Outcome Measure (pCMT-QOL Parent-Proxy Version) (ages 8-18), is a reliable, valid, and sensitive proxy measure of health-related QOL for children ages 8 to 18 with CMT. Validation is published here.
- Parent-Proxy Pediatric Charcot-Marie-Tooth Disease Quality of Life Outcome Measure (pCMT-QOL Parent-Proxy Version) (ages 0-7). is a reliable, valid, and sensitive proxy measure of health-related QOL for children ages 8 to 18 with CMT. Validation is published here.

The CMT-Health Index (CMT-HI) (ages 18 years and over) is a reliable, valid, and sensitive measure of health-related QQL for adults with CMT. Validation is published here.

Disease Mutation Databases

Over 130 genes are associated with CMT and related disorders and new genes continue to be discovered. The below databases help facilitate the search for disease-causing mutations.