CMT1X
CMT1X is one of the most common forms of CMT. It is caused by changes in the GJB1 gene on the X chromosome, and because of how X-linked conditions are passed down, it usually affects males more consistently than females.
What CMT1X is
CMT1X is caused by changes in the GJB1 gene, which makes a protein called connexin 32. Connexin 32 forms tiny channels that let Schwann cells, the cells that build and maintain myelin, pass nutrients and signals across the layers of insulation around a nerve.
When connexin 32 does not work, both the myelin and the underlying nerve fiber suffer, so CMT1X often shows a mix of demyelinating and axonal features on nerve testing, sitting between the classic type 1 and type 2 patterns.
GJB1 sits on the X chromosome, and that changes who is affected and how. Men, who have a single X, tend to have clearer, earlier, and more uniform symptoms. Women, who have two X chromosomes, range from having no symptoms to being as affected as men, so a family history can look almost dominant.
How common it is. CMT1X is generally considered the second or third most common form of CMT after CMT1A, accounting for about 10 to 13 percent of genetically confirmed cases in large patient cohorts.
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 muscle wasting starting in the feet and lower legs, usually more pronounced in men
- High arches, hammertoes, foot drop, and reduced or absent ankle reflexes
- Reduced sensation in the feet and, over time, the hands
- Symptoms in women that range from none to as severe as in men
- Occasionally, brief episodes of central nervous system symptoms (such as temporary trouble speaking or weakness), which typically resolve
Onset and how it changes over time
CMT1X often begins in childhood or the teenage years in men, with the familiar CMT picture of foot drop, high arches, and difficulty running. In women, onset is frequently later and milder, and some women only learn they carry the change when a male relative is diagnosed.
Like most forms of CMT, CMT1X is slowly progressive and does not shorten life expectancy for the great majority of people. Because women can be mildly affected or symptom-free yet still pass it on, understanding the inheritance is especially useful for families.
How it is inherited
CMT1X is inherited in an X-linked pattern, because the GJB1 gene sits on the X chromosome. A man passes his single X to all of his daughters (who will carry the change) and to none of his sons (who receive his Y instead). A woman who carries the change has about a 1 in 2 chance of passing it to each child, son or daughter. Unlike many X-linked conditions, women here are often affected, not just carriers, which is why a genetic counselor can help map what it means for your family.
X-linked inheritance
The changed gene sits on the X chromosome. A carrier mother passes it to about half of her sons, who are usually affected, and half of her daughters, who are carriers and may have milder symptoms.
- 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 CMT1X?
CMT1X is one of the most common forms of Charcot-Marie-Tooth disease. It is caused by changes in the GJB1 gene, which makes a protein called connexin 32 that forms tiny channels letting Schwann cells pass nutrients and signals across the layers of insulation around a nerve. When connexin 32 does not work, both the myelin and the underlying nerve fiber suffer, so CMT1X often shows a mix of demyelinating and axonal features, sitting between the classic type 1 and type 2 patterns.
What gene causes CMT1X?
CMT1X is caused by changes in the GJB1 gene, which makes connexin 32. GJB1 sits on the X chromosome, and that changes who is affected and how. A genetic test can confirm your subtype.
What are the symptoms of CMT1X?
CMT1X usually starts with weakness and muscle wasting in the feet and lower legs, along with high arches, hammertoes, foot drop, reduced or absent ankle reflexes, and reduced sensation in the feet and, over time, the hands. Symptoms are usually more pronounced in men, while women range from having no symptoms to being as severely affected as men. Occasionally people have brief episodes of central nervous system symptoms, such as temporary trouble speaking or weakness, which typically resolve.
How is CMT1X inherited, and will my children get it?
CMT1X is inherited in an X-linked pattern, because the GJB1 gene sits on the X chromosome. A man passes his single X to all of his daughters (who will carry the change) and to none of his sons. A woman who carries the change has about a 1 in 2 chance of passing it to each child, son or daughter. Unlike many X-linked conditions women here are often affected, not just carriers, which is why a genetic counselor can help map what it means for your family.
Does CMT1X affect men and women differently?
Yes. Because GJB1 sits on the X chromosome, men, who have a single X, tend to have clearer, earlier, and more uniform symptoms, often beginning in childhood or the teenage years. Women, who have two X chromosomes, range from having no symptoms to being as affected as men, so onset is frequently later and milder and some women only learn they carry the change when a male relative is diagnosed. Like most forms of CMT, CMT1X is slowly progressive and does not shorten life expectancy for the great majority of people.
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 (Charcot-Marie-Tooth overview, NBK1358) and OMIM 302800. Verified 2026-07-08.