CMT2C
CMT2C is a rarer axonal form caused by changes in the TRPV4 gene. What sets it apart is that it can affect more than the limbs: the voice box, the breathing muscles, and hearing can be involved, so it calls for a broader eye than most forms of CMT.
What CMT2C is
CMT2C is caused by changes in the TRPV4 gene, which makes a channel that lets calcium and other ions flow in and out of cells and helps them sense pressure, stretch, and temperature. The same gene is linked to a group of related conditions affecting nerves, muscles, and bone.
In its neuropathy form, TRPV4 causes an axonal CMT, damaging the nerve fibers themselves. But unlike most forms of CMT, which stay in the arms and legs, CMT2C can also involve the nerves to the voice box and the diaphragm, and sometimes hearing.
This broader reach is the defining feature. Alongside the usual distal weakness, some people have vocal cord weakness (a hoarse or breathy voice), breathing difficulty, hearing loss, or skeletal differences such as scoliosis, and weakness of the shoulder girdle as well as the lower legs (a scapuloperoneal pattern).
How common it is. CMT2C is a rare form of CMT, notable less for its frequency than for its ability to affect the voice, breathing, and hearing.
Common signs and symptoms
Reported symptoms and their severity vary from person to person, even within the same family. This is a general picture, not a prediction for any one person.
- Weakness and wasting in the lower legs, and often the shoulder-girdle muscles (a scapuloperoneal pattern)
- Vocal cord weakness causing a hoarse, weak, or breathy voice in some people
- Breathing difficulty when the diaphragm is involved, which needs monitoring
- Hearing loss in some people
- Skeletal differences such as scoliosis or contractures, and sometimes short stature
Onset and how it changes over time
CMT2C is highly variable. It can be present from birth with breathing or vocal cord problems, or begin later and more mildly. Because the voice box and breathing muscles can be involved, some presentations are more serious than the typical limb-only forms of CMT.
The wide range means CMT2C really calls for a care team that looks beyond the feet and hands, including attention to voice, breathing, and hearing where needed. Severity differs greatly from person to person, so an experienced team is the best guide.
How it is inherited
CMT2C is inherited in an autosomal dominant pattern, so a single changed copy of TRPV4 is enough to cause it, and an affected parent has about a 1 in 2 (50 percent) chance of passing it to each child. Even within one family, though, how it shows up can vary widely. New changes also occur. A genetic counselor can help you understand the range and what to watch for.
Autosomal dominant inheritance
One changed copy of the gene is enough to cause CMT. A parent who has it passes it to about half of their children, on average, sons and daughters alike.
- Affected
- Carrier
- Unaffected
- Male
- Female
This diagram shows a typical family. Real families vary, and it does not predict any specific outcome. A genetic counselor can walk through what it means for yours.
Frequently asked questions
What is CMT2C?
CMT2C is a rarer axonal form of Charcot-Marie-Tooth disease caused by changes in the TRPV4 gene. What sets it apart is that it can affect more than the limbs: the voice box, the breathing muscles, and hearing can be involved, so it calls for a broader eye than most forms of CMT. To confirm which subtype you have, genetic testing is the way to know for certain.
What gene causes CMT2C?
CMT2C is caused by changes in the TRPV4 gene, which makes a channel that lets calcium and other ions flow in and out of cells and helps them sense pressure, stretch, and temperature. The same gene is linked to a group of related conditions affecting nerves, muscles, and bone. In its neuropathy form, it causes an axonal CMT that damages the nerve fibers themselves.
What are the symptoms of CMT2C?
Alongside the usual weakness and wasting in the lower legs, CMT2C often involves the shoulder-girdle muscles as well (a scapuloperoneal pattern). Its defining feature is a broader reach: some people have vocal cord weakness causing a hoarse or breathy voice, breathing difficulty when the diaphragm is involved, or hearing loss. Skeletal differences such as scoliosis, contractures, or short stature can also occur.
How is CMT2C inherited, and will my children get it?
CMT2C is inherited in an autosomal dominant pattern, so a single changed copy of TRPV4 is enough to cause it, and an affected parent has about a 1 in 2 (50 percent) chance of passing it to each child. Even within one family, though, how it shows up can vary widely, and new changes also occur. A genetic counselor can help you understand the range and what to watch for.
Is CMT2C serious?
CMT2C is highly variable. It can be present from birth with breathing or vocal cord problems, or begin later and more mildly, and because the voice box and breathing muscles can be involved, some presentations are more serious than the typical limb-only forms of CMT. The wide range means CMT2C really calls for a care team that looks beyond the feet and hands, including attention to voice, breathing, and hearing where needed.
Confirm your subtype
If you have a clinical CMT diagnosis but no confirmed gene, genetic testing is how you learn your subtype. CMT Genie helps you and your provider get tested and connects you with telehealth genetic counseling.
Clinical information on this page is based on GeneReviews (Autosomal Dominant TRPV4 Disorders, NBK201366) and OMIM 606071. Verified 2026-07-08.