Humans have about 22,000 genes. These are grouped together on 23 paired chromosomes: 23 single chromosomes from your mother and 23 from your father. And, apart from the sex cells – sperm and unfertilised eggs – every single human cell has a full copy of these 46 chromosomes in 23 pairs.
In contrast, the sperm and egg cells each only have a single set of chromosomes. When a sperm cell fertilises an egg, the two sets combine, forming a new cell, with the double set. This cell then multiplies, creating a new individual with 10,000 trillion cells, each one containing a copy of the original 23 pairs of chromosomes.
In this way genes, including faulty ones (mutations), are passed on down through the generations. Not all faulty genes will have an effect. It all depends on the inheritance patterns of that single gene.
Some faulty genes are dominant, which means that you only need one faulty gene to have CMT. In effect, the dominant gene over-rules the instructions from the ‘good’ gene.
The most common forms of CMT in the UK are dominant, including most forms of CMT1 and CMT2.
If you have a dominant form of CMT, you have a 50:50 chance of passing on the faulty gene to any children. If they inherit it, they will usually develop the symptoms of CMT.
Dominant inheritance (AD) (Most types of CMT1 and CMT2)
Dominant [Affected + Unaffected]
With each pregnancy, this couple has a 50:50 chance of having a child with CMT, whatever the child’s sex.
If a faulty gene is recessive it means that you need two copies of the same faulty gene (one from each parent) before you could develop CMT.
If you have only one faulty recessive gene you are known as a carrier. You will not develop CMT, but you have a 50:50 chance of passing on your faulty gene to your children. If they inherit it, they will only get CMT if they inherit a second faulty gene from the other parent.
Some forms of both CMT1 and CMT2 are recessive.
If your CMT is caused by two faulty recessive genes, you will definitely pass on one of your faulty genes to your children. But unless they inherit the same faulty gene from the other parent, they will only be a carrier.
If both parents are carriers for the same recessive gene (i.e. they each only have one copy), their children have a one in four chance of developing CMT (by inheriting two copies of the gene) and a 50 per cent chance of being carriers (by inheriting one copy of the gene).
Of your 23 pairs of chromosomes, the 23rd pair is known as the pair of sex chromosomes, X and Y. If you inherit two X chromosomes you become a woman and if you inherit an X and a Y you become a man.
Four faulty genes responsible for CMT have been discovered on the X chromosome. Men who get X-linked CMT are often more severely affected than women.
X-linked inheritance (CMTX)
X-linked mother (who would usually have mild CMT) + unaffected father
Genes can change (mutate) ‘out of the blue’. If this happens, future generations will be exposed to the risk of inheriting the changed gene in just the same way as described above.
About one in 20 people with CMT1A have a new genetic mutation, but these are much more commonly seen with other types of CMT, for example CMT2A.
The term sporadic is used when someone with CMT apparently has no family history (i.e. no other family members are affected). There are a number of possible reasons for this:
You can inherit CMT in one of the following ways: