What is Dominant Intermediate CMT (DI-CMT)?
The classification of DI is used for people who have dominant forms of CMT that cause intermediate slowing, so nerve conductions that are slower than 50, but not classically slow like 20-25 m/s, but somewhere in the middle of that, like 30s. There is a whole group of CMT-DI forms, including one called Charcot Marie Tooth disease, Dominant Intermediate type E (CMT-DIE), which causes kidney failure. Other genes are CMT-DIC which is YARS, MPZ can sometimes fall in to this category as it is referred to as CMT-DID, so some of these genes are unique and some are crossover to more classic forms of CMT. Nevertheless, YARS has lots of variants, but not all are disease causing. Please consult with a certified genetic counselor for a correct diagnosis. Read more about DI-CMT.
How accurate are DNA blood tests for detecting CMT?
Genetic tests, which are done by drawing blood, are available to test for many, but not all, common chromosomal defects that cause CMT. A positive genetic test can provide a definitive diagnosis and useful information for family planning. However, a negative result does not rule out CMT, since some types cannot yet be tested using DNA sampling. Currently, 27 types can be identified by DNA testing, including: 1A, 1B, 1C, 1D, 1E, 1F, 1X, 2A, 2B, 2E, 2F, 2I, 2J, 2K, 4A, 4C, 4E, 4F, 4J, HNPP, CHN, and DSN. Each lab can inform you about the accuracy of its testing, but all of them are probably >99% for the specific test being done.
How much does it cost to find out what type of CMT I have? Where do you go for testing? Our last blood rests were 18 years ago.
There are currently 27 CMT types that can be identified through DNA testing, many more than 18 years ago. Please click here for more information on genetic testing and CMT: https://www.cmtausa.org/living-with-cmt/find-help/genetic-testing
Since genetic tests look for the first gene mutation, how does one know if there are additional mutations?
It is rare to have two types of CMT as the person affected would need mutations in two or more genes that each cause CMT.
Since CMT is primarily hereditary, is it beneficial for patients to be seen as a family unit instead of visiting adult and pediatric clinics?
In a perfect world, yes, this would be ideal, but not all the Centers of Excellence are equipped for both pediatrics and adults. However, a few do cater to families. See: https://www.cmtausa.org/living-with-cmt/find-help/cmta-centers-of-excellence
My neurologist diagnosed me with CMTX and said that even if my children received the mutation for CMT there was still a chance that they would just be CARRIERS—they would never show symptoms but could pass it on to their children. I had never heard that before and don’t understand what would control whether they had symptoms or just carried the mutation. Please elaborate.
Females have two X chromosomes. A woman affected with CMT1X has a 50/50 chance of passing on the X chromosome with the changed gene in each pregnancy, no matter the sex of the child. Traditionally, females have been thought to have no to mild symptoms, but we have seen women whose symptoms resemble those of their male relatives. Overall, the severity is less than males, but females can, and usually do, have symptoms. This is likely because while one gene isn’t working, the other copy of the gene on the other X-chromosome is working well and makes up for the other one.
A male offspring, on the other hand, has one X chromosome and one Y chromosome. If he inherits the copy of the X-chromosome with non-working gene from his mother, he has no other X chromosome to compensate, and he will develop CMT.
Can I use 23andMe genetic testing to see if I have CMT?
23andMe’s genetic testing will not be helpful in detecting CMT. While this type of testing is approved to look for some conditions, such as Bloom syndrome, CMT is not one of them. Moreover, 23andMe testing does not perform a full gene sequence of any conditions, nor is it certified to be used for clinical actionability. This means that if a condition is found using 23andMe testing, that finding would still need to be confirmed in a CLIA-certified lab before the information could be used for clinical purposes (such as treatment or clinical trials).
Instead, get tested at a genetic testing company because they do test for CMT. Additionally, those labs are CLIA-certified, which means that they have passed government inspection of their processes and proven that they can perform the specific test with almost zero false positives or negatives (genetic testing has a 99.9% success rate). Also, genetic testing companies have specialized individuals who work on variant interpretation with intimate knowledge of the genes and variants tested. This is important because the genetic testing itself is not usually the hard part; the challenge lies in the analysis of those results. Interpretation by a specialized team is vital to procuring accurate results that provide personally and clinically meaningful information to patients and families.
Genetic testing does not need to be expensive. Ask your health care professionals about different laboratories that provide genetic testing services to patients at low out-of-pocket cost. Also, note that many insurances will cover genetic testing, particularly if testing is sought for family planning purposes or if the results of testing could change management. To find a genetic counselor, go to www.nsgc.org.
What do mutations in the LMNA gene mean?
Mutations in the LMNA gene can cause symptoms that are typical of CMT as well as symptoms that are not so typical, such as weakness in the parts of the limbs close to the body (e.g. the upper thigh). It is difficult to state what any given mutation in the gene will do. A small fiber neuropathy can cause sensory symptoms, including pain, and can be caused by mutations in the LMNA gene. It is possible that your symptoms are due to CMT, but it is also possible that they are due to a different cause of neuropathy. Your doctor, or a CMT specialist, may be able to help determine the cause of your symptoms.
I’m curious about CRISPR, a very interesting tool/method to fix defective genes. Supposedly it’s cheap, very effective, and can be used on humans. Have our research teams thought about looking into this for CMT?
CRISPR CAS in a new and amazing technology that can manipulate genes far easier than older techniques. The CMTA has used CRISPR CAS to make a CMT2A rat – the first animal model of CMT2A. Although CRISPR CAS may be useful to treat some genetic diseases, whether it will have an application for a kind of CMT remains to be determined.