The CMT Name Game
Updated: Jan 18
Did you know that there is a method behind the madness of the naming of the various CMT subtypes? It’s fairly straightforward, too. Whether you’re brand new to CMT, a seasoned pro, or you’re somewhere in the middle, this is an article for you, and it might help to shed some light on the why’s of the CMT name game.
There are 4 basic Type categories/classifications, currently, as of this writing. They are 1, 2, 4, and X-Linked. Additionally, there is Dominant Intermediate and Recessive Intermediate. Things in the CMT world move and change rapidly. New gene associations are being discovered almost daily. The names are subject to change at any moment. However, there is still a general method to the madness of the CMT name game that seems to be generally followed.
The names, as you know, have a number, followed by a letter. There are exceptions to that rule, but this is the general rule. What do they mean though? What is this secret? There’s no secret, and it’s surprisingly straightforward.
The Type 1s, or CMT 1, are all a demyelinating subtype that are each autosomal dominant in inheritance, with one exception. I’ll explain that exception in a moment.
The Type 2s, or CMT 2, are all an axon related subtype that are also autosomal dominant. The European classification includes a few exceptions for the Type 2s, and I’ll explain those in a moment.
The Type 4s, or CMT 4, are each autosomal recessive in inheritance, and the subtype can be demyelinating or it can be axon related.
The X-Linked Types, or CMTX, are each caused by a mutation in a gene that is found on the X Chromosome. These, thus far, are each a demyelinating subtype. They can be either dominant or recessive, and are termed X-Linked Dominant or X-Linked Recessive. With the X-Linked subtypes, the letter comes before the number, but the letter is always “X” to signify X-Linked CMT. Now that we know what the 4 basic groups are, what do the letters represent? That’s even easier to explain.
The letter that appears after the number, i.e., 1A, 2D, 4J, correlates with the order in which the associated gene mutation was identified. A is the first, B is the second, and so on. In the example, CMT1A, it’s a demyelinating subtype whose gene mutation was the first to be identified for this type, and it has a dominant inheritance pattern. In the example, CMT2Z, it’s an axon related subtype whose gene mutation was the 26th to be identified for this type, and it has a dominant inheritance pattern.
Basically, the number denotes whether it’s demyelinating and dominant, axon related and dominant; or demyelinating or axon related and recessive. The letter tells us the order (first, second, third) that the causative gene mutation was discovered for that number. And, then, there’s the X-Linked types.
In X-Linked CMT, or CMTX, the X is first and is followed by a number (1, 2, 3, etc.). In the example, CMTX1, it’s an X-Linked subtype whose gene mutation was the first to be identified for the X-Linked types. Easy-peasy.
Remember the exceptions I mentioned? Here’s the exceptions to the rule. Remembering that the CMT 1’s are each demyelinating and dominant in inheritance, 1F is caused by a gene mutation that can be dominant or recessive. You’ll sometimes see 1F expressed as 1F/2E (2E/1F, depending on the author) because they share the same gene. Researchers have not yet been able to nail down a clarification. Also, HNPP (Hereditary Neuropathy with liability to Pressure Palsy) is a subtype that is included in the Type 1s.
In the European classification, there are several (7) recessive subtypes included in the Type 2’s because they are each axon related. There are an additional 2 subtypes in the group that are known to be either dominant or recessive in inheritance.
There are 2 groups that don’t have a number. They are grouped according to their Nerve Conduction characteristics. Subtypes in these 2 groups cross the boundary and overlap between that which is seen in demyelinating subtypes and that which is seen in axon related subtypes. These are the Intermediate CMT subtypes.
The Intermediate Types are classified according to their respective inheritance pattern, followed by a letter, starting with, “A,” that denotes the order in which the responsible gene mutation was identified, just as in the other groups. Subtypes in these groups are either dominant or recessive, and they are divided accordingly.
The Dominant Intermediate subtypes are named CMTDI, and then the respective letter. They are expressed as CMTDIA, CMTDIB, etc. The Recessive Intermediate subtypes, in turn, are expressed as CMTRIA, CMTRIB, etc.
As with everything else that is CMT, there is always an exception to the rule with even the names of the subtypes. I used the reference to the European classification system because I’m in the States, and, as a patient, I don’t necessarily follow the classifications outside of the States. However, I don’t want to leave anybody out.
What I described here is essentially widely accepted for the various subtypes of CMT, but there may be differences where you live. I’m not a physician or a clinician, and translating differences into what I described and know the classifications to be is not something I’m qualified for.
The Intermediate subtype classifications are somewhat newer. The CMTA website does not list these, and the MDA website gives only a two-sentence description. Because people are diagnosed with these, I couldn't leave them out. The genetics and diagnostics of CMT, ergo the naming of subtypes, is moving at a breakneck speed. New causative gene mutations are being discovered almost daily. These new discoveries have a tendency to jostle subtype names around in a confusing manner. It’s almost impossible for any one individual or organization to keep up.
To add some confusion and chaos to the mix, there are some who have been diagnosed with more than one CMT subtype. Albeit rare, this can happen because it's possible to have more than one causative gene mutation. My question when this happens: does having more than one causative gene mutation constitute its own subtype, or is this really two individual known subtypes that are complicating each other? I would love to know your thoughts. I invite you to share your view in the comments below.
I hope that, in the very least, I’ve been able to shed a little light on the CMT name game and to maybe provide a little bit of insight into why yours is called 2B, or 4C, or X1, or CMTDIB. While the name your subtype has might be confusing, I hope I’ve been able to remove some of that confusion.
For an in-depth discussion and explanation of the inheritance patterns of CMT, I invite you to join The Inheritance Patterns of CMT discussion.