Charcot Marie Tooth
An insight into my condition
Introduction
What are we made of?
The basic structural unit of all living organisms is the cell. Our bodies are made from billions of cells which combine and work together to make every part of our body. Cells have different roles within the body. Cells that perform similar tasks group together to form tissues, such as your kidneys, liver and muscle.
An essential structure within the cell is the nucleus which contains the genetic material that determines all of our characteristics. This genetic information is called DNA or deoxyribonucleic acid. DNA can be likened to coded information which is passed on from generation to generation. It consists of thousands of units called nucleotides consisting of a base (4 types, A, C, G, and T), a sugar and a phosphate. Two strands of nucleotides join to form a ladder like structure which is then twisted into a characteristic double helix.
This coded information is organised on chromosomes. Each chromosome contains the code for hundreds of different genes. Genes are the basic unit of inheritance that determine our make-up. Genes come in pairs, one inherited from each parent. Most genes contain information specific for the production of a protein, eg – peripheral myelin protein 22 (PMP22), too much of which causes CMT Type 1a.
Inheriting genes
Humans have 23 pairs of chromosomes. One set of chromosomes comes from your mother and the other set from your father. The sex cells (the unfertilised egg and sperm) contain only 23 unpaired chromosomes each.
Fertilisation of a 23-chromosome egg by a 23-chromosome sperm produces a new 46-chromosome cell, which grows into a new individual. No two people (except identical twins) have the same set of DNA. Errors or mutations in genes can either be inherited or can arise “out of the blue”. Sometimes these errors have no obvious effect and at other times a single letter change, deletion or duplication (as in Type 1a) can have serious consequences.
You may have heard of the words “inheritance pattern”. This refers to the way in which the condition is passed on from generation to generation. There are three main types of inheritance (autosomal dominant, autosomal recessive and X-linked).
Inheritance Patterns
Autosomal dominant
Includes all the Type 1 CMT’s and most of the Type 2’s
Here the condition becomes apparent even though the affected person has only one abnormal gene. Either sex can have the condition and each child of an affected parent has a 50% chance of being affected.
However, the severity of the condition may vary considerably in different individuals. Some people are so mildly affected that they may not have recognised that they have the condition but they may then have a more severely affected child. So examination of all the family members is important as part of genetic counselling.
Autosomal recessive
Some Type 2 CMT’s and all Type 4 CMT's
These conditions become apparent only if both parents carry a faulty gene but the parents themselves do not manifest any symptoms. Each child of such parents has a 25% chance of carrying both abnormal genes and therefore of being affected. Either sex can have the condition.
The children of an affected individual are usually unaffected but cousin marriages between affected or unaffected members of such families greatly increase the risk that they will have affected children.
X-linked
(or sex-linked) - CMT Type 1X
These conditions are determined by genes which are carried on one of the chromosomes which control the sex of a child. The result is that only boys are affected and they inherit the disease from their mothers who are known as carriers.
Carriers are capable of passing the condition on to their own sons.
Women who carry the gene can either be completely unaffected, in which case they tend to be known as "carriers"; or they may be mildly affected, or they may have the condition as severely as males. This is because all female mammals have a problem with gene dosage. Each adult woman when she was an embryo randomly suppressed one or other of her X chromosomes in each cell in her body. If she carried the variant gene on the X chromosome, then it may be that this X chromosome is active in most cells in the relevant tissue, e.g. nerve cells, leading to neuropathy. Each son of a carrier has a 50% chance of having CMT 1X and each daughter has a 50% chance of being a carrier.
Unaffected boys cannot transmit the disease: however, the daughters of a man with X-linked CMT are all carriers.
What is Genetic mutation?
This is an unpredictable change in the structure of a gene causing a different characteristic to appear for the first time in a family. In about a 10% of those who have CMT Type 1a, it is due to genetic mutation. Subsequent generations will inherit the condition in an autosomal dominant pattern.
Can CMT be identified in the unborn child tested for in pregnancy?
Research on gene probes has made the diagnosis of CMT Type 1a possible in early pregnancy. Although these tests on the unborn child can be done from the tenth week of pregnancy onwards, investigations of some family members may be required before the prenatal tests are done. However, unless an individual is absolutely certain that an affected foetus would be aborted, there is no real advantage in discovering at this stage if the child is likely to be affected.
