It is caused by variants in the MME gene, which makes the enzyme neprilysin.

Genetic Testing for Charcot-Marie-Tooth Type 2T: What the MME Gene Shows

Q: How is it inherited?

CMT2T is usually autosomal recessive: a person inherits an altered copy of MME from each parent, and carrier parents typically have no symptoms. Rare MME variants have also been linked to late-onset neuropathy in a dominant pattern, where one altered copy may be enough. A genetic counselor can explain what a specific result means for relatives.

Medically reviewed by Brandon Colby, MD, last reviewed Jan 27, 2026

Charcot-Marie-Tooth disease axonal type 2T (CMT2T) is an adult-onset neuropathy caused by pathogenic variants in the MME gene. It is usually inherited in an autosomal recessive pattern, although rare MME variants have also been linked to late-onset autosomal dominant neuropathy. Genetic testing can help confirm the diagnosis.

Understanding Charcot-Marie-Tooth Disease Axonal Type 2T

Charcot-Marie-Tooth disease (CMT) is a group of inherited conditions that damage the peripheral nerves. Type 2 forms mainly damage the axon, the long fiber that carries the nerve signal.

CMT2T is caused by pathogenic variants in the MME gene, which provides instructions for making neprilysin, an enzyme on the surface of cells that breaks down small proteins called peptides. It is usually inherited in an autosomal recessive pattern, although rare MME variants have also been linked to late-onset autosomal dominant neuropathy.

Symptoms usually begin in adulthood, often between the 30s and 50s, and include weakness, muscle wasting and reduced sensation in the feet and lower legs. Because symptoms can be subtle at first, CMT2T may be mistaken for other causes of neuropathy.

Diagnosing Charcot-Marie-Tooth Disease Axonal Type 2T

A neurological exam and nerve conduction studies can help identify an axonal neuropathy. MME is one of the more common genetic causes of recessive CMT2 in some populations and is included on many CMT gene panels. Finding pathogenic variants in both copies of the MME gene can help confirm autosomal recessive CMT2T, while a single pathogenic variant may be relevant in late-onset autosomal dominant neuropathy.

Uses of Genetic Testing for Charcot-Marie-Tooth Disease Axonal Type 2T

Genetic testing for CMT2T can be helpful in several ways:

Confirming the diagnosis: Finding pathogenic variants in the MME gene can help clarify the diagnosis and may provide answers after a long search.
Separating CMT subtypes: Several forms of CMT cause similar symptoms. A genetic result can help identify the subtype and guide discussions about care and possible symptoms.
Family screening and counseling: Genetic results can help clarify the inheritance pattern and guide testing for relatives. A genetic counselor can explain the results, discuss risks to family members and review family planning options.
Research and clinical trials: Some research studies and trials enroll people by gene. A confirmed genetic diagnosis can make it easier to find studies that fit.

Advancements in Genetic Research for Charcot-Marie-Tooth Disease

Neprilysin helps break down amyloid beta in the brain and is also a target of some heart failure medicines that block its activity. Researchers are still learning how reduced neprilysin function affects peripheral nerves, and genetic findings from families with CMT2T help guide this work.

Get Tested With Whole Genome Sequencing

Whole genome sequencing reads 100% of your DNA, which includes the genes linked to Charcot-Marie-Tooth disease. Sequencing's Kit Bundles include a Whole Genome Sequencing kit and Next Gen Disease Screening, which analyzes your genome for more than 15,000 conditions. Bring your results to your doctor or a genetic counselor to help guide next steps.

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Frequently Asked Questions About Charcot-Marie-Tooth Disease Axonal Type 2T

What is CMT axonal type 2T?

It is an inherited axonal neuropathy that usually begins in adulthood and causes weakness, muscle wasting and sensory loss that start in the feet and lower legs.

What causes it?

It is caused by pathogenic variants in the MME gene, which makes the enzyme neprilysin.

What are the symptoms?

Symptoms include weakness and wasting in the lower legs, foot drop, trouble walking, reduced reflexes and numbness or tingling in the feet. Symptoms often start in mid-adulthood and progress slowly.

How is it inherited?

CMT2T is usually inherited in an autosomal recessive pattern: a person inherits a pathogenic variant in the MME gene from each parent, and carrier parents typically have no symptoms. Rare MME variants have also been linked to late-onset neuropathy in an autosomal dominant pattern, although not everyone with a single variant develops symptoms. A genetic counselor can explain what a specific result means for relatives.

How is it diagnosed?

A neurologist usually starts with a medical and family history and an exam of strength, reflexes and sensation. Nerve conduction studies and electromyography (EMG) show how well nerves carry signals and whether the problem mainly affects the myelin coating or the nerve fiber (axon). Genetic testing can then confirm the specific cause.

Is there a treatment?

There is currently no cure, but care can help people stay active and independent. Physical and occupational therapy, ankle-foot orthoses (braces), supportive footwear, orthopedic surgery for foot deformities and pain management are commonly used. A neuromuscular specialist can build a care plan with you.

Does Sequencing test for this condition?

Whole genome sequencing reads 100% of your DNA, which includes the MME gene discussed in this article. Sequencing's Kit Bundles include Next Gen Disease Screening, which analyzes your genome for more than 15,000 conditions. You can also upload DNA data from another test for free and search it in Genome Explorer. Results describe variants, not a diagnosis.

Where can I find support or a specialist?

Patient organizations such as the Charcot-Marie-Tooth Association, Hereditary Neuropathy Foundation and Muscular Dystrophy Canada offer education and support for people and families affected by CMT, and several publish directories of CMT clinics or specialists. They are listed in the resources below, along with an expert written overview from GeneReviews.

Resources

These organizations and resources are provided for education and support. They are not endorsements or medical advice.

Charcot-Marie-Tooth Association (United States): a patient and family organization for all types of CMT.
CMTA: Find a specialist: the organization's directory of clinics or specialists.
CMTA: Advisory Board: the medical and scientific advisors who guide the organization.
Hereditary Neuropathy Foundation (United States): a patient organization for people and families affected by CMT and other inherited neuropathies.
HNF: Find a specialist: the organization's directory of clinics or specialists.
HNF: Scientific Advisory Board: the medical and scientific advisors who guide the organization.
Muscular Dystrophy Canada (Canada): a neuromuscular disease organization that supports people with CMT in Canada.
Muscular Dystrophy Canada: Medical and Scientific Advisory Committee (MSAC): the medical and scientific advisors who guide the organization.
GeneReviews: Charcot-Marie-Tooth Hereditary Neuropathy Overview (NCBI Bookshelf): an expert written clinical overview of CMT and its genetics.

References

Higuchi Y, Hashiguchi A, Yuan J, et al. Mutations in MME cause an autosomal-recessive Charcot-Marie-Tooth disease type 2. Ann Neurol. 2016;79(4):659-672. doi:10.1002/ana.24612
Auer-Grumbach M, Toegel S, Schabhüttl M, et al. Rare variants in MME, encoding metalloprotease neprilysin, are linked to late-onset autosomal-dominant axonal polyneuropathies. Am J Hum Genet. 2016;99(3):607-623. doi:10.1016/j.ajhg.2016.07.008

This article is for education and is not a substitute for professional medical advice, diagnosis, or treatment. Talk to a qualified healthcare provider about your own health.