Charcot-Marie-Tooth disease (CMT) is named after the three doctors who first described the disease in 1886: Jean-Martin Charcot (shar-coh), Pierre Marie, and Howard Henry Tooth. Today, CMT refers to any peripheral neuropathy with a genetic cause, whether or not the specific genetic change is known.
CMT is a rare, multisystem, multiorgan disease that causes lifelong, progressive symptoms, including muscle weakness and atrophy in the arms and legs, sensory loss, and other complications. These symptoms often lead to challenges with balance, walking, hand use, and other daily activities.
Genetics plays a central role in CMT. Every type of CMT is caused by a change in a gene. Genetic testing can help identify these changes and provide important information about a person’s diagnosis, subtype, and inheritance pattern. This page is designed to help you understand what genetic testing is, what it can (and can’t) tell you, and how to have an informed conversation with your healthcare provider.
What Causes CMT?
CMT is caused by changes, or variants, in genes that affect the peripheral nerves. The peripheral nerves carry signals between the brain, spinal cord, and the rest of the body. When the genes responsible for peripheral nerve function are altered, the nerves can’t send signals properly, leading to CMT symptom onset. More than 130 genes have been linked to CMT, and this number grows every year.
What Is Genetic Testing for CMT?
Genetic testing is a medical test that looks for changes in your DNA. In CMT, it’s used to find out which genetic change is responsible for your symptoms. This can confirm your clinical CMT diagnosis, guide family planning, and support eligibility for research or clinical trials.
Should Everyone With CMT Get Genetic Testing?
Genetic testing is a personal decision, and there’s no one-size-fits-all answer. Some people pursue testing to confirm a diagnosis, identify their subtype, or plan for the future. Others may choose not to test for various reasons. A qualified healthcare provider can help you discuss your options and decide what makes the most sense for you.
What Types of Genetic Tests are Used for CMT?
Different types of genetic tests can be used to look for the cause of CMT. Each test works a little differently, and your healthcare provider will order the test they feel is best for you.
- Single-gene testing: Looks for changes in one specific gene. This may be used when symptoms strongly suggest a certain subtype linked to a known gene or when another family member has genetic confirmation for their CMT.
- Multi-gene panel testing: Looks at many genes known to be associated with CMT, all at once. These panels vary by lab and may not include every possible gene.
- Whole-exome sequencing (WES): Examines the parts of your DNA that provide instructions for making proteins. These are the “coding regions” of all genes. WES can sometimes find rare changes that panel tests miss, but it doesn’t catch everything.
- Whole-genome sequencing (WGS): Examines all parts of all genes, including coding and non-coding regions. This test is used in research studies and is not typically ordered in clinical settings.
What Can the Results of Genetic Testing Tell Me?
Genetic testing can provide different types of information, depending on your situation. Results may help:
- Confirm a clinical CMT diagnosis
- Identify your specific genetic subtype, which may inform eligibility for research or clinical trials
- Provide insight into medical management
- Support informed family planning
- Help identify the inheritance pattern and provide information for at-risk family members
While genetic test results can explain the underlying cause of CMT, they cannot reliably predict how the disease will progress or how severe it will become. CMT symptoms vary widely, even among individuals with the same genetic change.
What Are the Benefits and Limitations of Genetic Testing?
The main benefit of genetic testing is confirming a clinical diagnosis. A positive result identifies the subtype and can help with family planning decisions. In some cases, testing may not find the genetic cause. This doesn’t rule out CMT; it simply means the responsible gene wasn’t included in the test or hasn’t been discovered yet.
How Can I Get Genetic Testing for CMT?
Genetic testing for CMT starts with a conversation with a qualified healthcare provider. This may be your family doctor, a neurologist, a geneticist, or a certified genetic counselor. They can help you decide if testing makes sense for you, explain what the process involves, and walk you through the results. CMTA Centers of Excellence are multidisciplinary clinics that have CMT genetic testing expertise. Each CMTA Center of Excellence provides comprehensive specialty care and can help navigate the genetic testing landscape.
