CMT6
CMT6 is a rare form defined by the combination of CMT with optic atrophy, a thinning of the nerve to the eye. It is caused by changes in the MTRFR gene, formerly called C12orf65, which the mitochondria need to make energy.
What CMT6 is
CMT6 is caused by changes in the MTRFR gene, once known as C12orf65. This gene helps mitochondria, the cell energy factories, finish making their own proteins. When it does not work, energy production stalls in the cells that need it most, including the long nerves of the limbs and the optic nerve to the eye.
What sets CMT6 apart is that it usually affects vision as well as the limbs. In many people the first sign is childhood-onset optic atrophy, a fading of the optic nerve that reduces the sharpness of vision, followed by the weakness and sensory loss of an axonal neuropathy.
Because it comes from a mitochondrial energy problem, some people also develop other features over time, such as unsteadiness (ataxia), and at the more severe end of the spectrum, spasticity or learning difficulty. The combination of nerve and eye involvement is the defining clue.
How common it is. CMT6 is rare, and it is distinguished within CMT by the combination of peripheral neuropathy and optic atrophy.
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.
- Optic atrophy, a thinning of the optic nerve that reduces vision, often the first sign in childhood
- Weakness and wasting of the feet and lower legs, with reduced reflexes and glove-and-stocking sensory loss
- Progressive loss of visual sharpness over time
- In some people, unsteadiness (ataxia) or, at the more severe end, spasticity or learning difficulty
Onset and how it changes over time
CMT6 often begins in childhood, and vision changes from optic atrophy are frequently the first thing noticed, sometimes before the limb weakness. Both the neuropathy and the visual loss tend to be progressive, and the visual impairment can become significant.
CMT6 sits on a spectrum, from a neuropathy-plus-optic-atrophy picture to more complex, more severe presentations. Because vision is involved, care benefits from including eye specialists alongside the neuromuscular team, and severity varies from person to person.
How it is inherited
CMT6 is inherited in an autosomal recessive pattern: it takes two changed copies of the MTRFR gene, one from each parent, who are usually unaffected carriers. When both parents carry a change, each child has about a 1 in 4 (25 percent) chance of being affected. A genetic counselor can explain what this means for siblings and family planning.
Autosomal recessive inheritance
It takes two changed copies, one from each parent, to cause CMT. When both parents are unaffected carriers, each child has about a 1 in 4 chance of being affected and a 1 in 2 chance of being a carrier.
- 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.
Faces of CMT
Real families living with CMT6, in their own words.
Jaxson Flynt · Jaxson's Crusaders
Diagnosed with an MTRFR gene defect as a toddler, Jaxson keeps meeting milestones doctors thought impossible.
Read their story ›
Zach Houliares · Zach's Team
After 14 years without answers, Zach was diagnosed with CMT6 and MTRFR mitochondrial disease.
Read their story ›Frequently asked questions
What is CMT6?
CMT6 is a rare form of CMT defined by the combination of peripheral neuropathy and optic atrophy, a thinning of the nerve to the eye. It is caused by changes in the MTRFR gene, formerly called C12orf65, which helps mitochondria, the cell energy factories, finish making their own proteins. When it does not work, energy production stalls in the cells that need it most, including the long nerves of the limbs and the optic nerve. If you want to confirm your subtype, genetic testing can identify it.
What gene causes CMT6?
CMT6 is caused by changes in the MTRFR gene, once known as C12orf65. The gene helps mitochondria complete the making of their own proteins, and when it fails, energy production stalls in the long nerves of the limbs and in the optic nerve to the eye. This is why CMT6 usually affects vision as well as the limbs.
How is CMT6 inherited?
CMT6 is inherited in an autosomal recessive pattern, meaning it takes two changed copies of the MTRFR gene, one from each parent, who are usually unaffected carriers. When both parents carry a change, each child has about a 1 in 4 (25 percent) chance of being affected. A genetic counselor can explain what this means for siblings and family planning.
What are the symptoms of CMT6?
What sets CMT6 apart is that the first sign is often childhood-onset optic atrophy, a fading of the optic nerve that reduces the sharpness of vision, followed by the weakness and sensory loss of an axonal neuropathy. People typically develop weakness and wasting of the feet and lower legs, reduced reflexes, and glove-and-stocking sensory loss. Some people also develop unsteadiness (ataxia) or, at the more severe end, spasticity or learning difficulty.
Is CMT6 progressive?
CMT6 often begins in childhood, and both the neuropathy and the visual loss tend to be progressive, with the visual impairment sometimes becoming significant. It sits on a spectrum, from a neuropathy-plus-optic-atrophy picture to more complex, more severe presentations, and severity varies from person to person. Because vision is involved, care benefits from including eye specialists alongside a neuromuscular team.
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 peer-reviewed literature (C12orf65 / MTRFR neuropathy with optic atrophy) and OMIM 613559. Verified 2026-07-08.