By Yolanda Smith, BPharm
Charcot-Marie-Tooth disease (CMT) is a health condition that is caused by a mutation in one of certain genes that result in damage the peripheral nervous system. Patients affected by CMT will experience symptoms such as muscle weakness and numbness in the limbs because of this damage to the nervous system.
There are many different causative gene defects that can cause CMT, and each has distinct characteristics as to its impact on the individual and the way it can be inherited from the parents.
Peripheral Nervous System Damage
There are two main components to the peripheral nerve cells: the axon and the myelin sheath. The axon transmits the electrical signals between the brain and the limbs, whereas the myelin sheath insulates the axon and protects the electrical signals within.
Depending on the specific gene mutation, the function of the axon may be inhibited or there may be degeneration of the myelin sheath. Both of these changes to the peripheral nerve cells result in abnormal transmission of the messages between the brain and the muscles or senses. As a result, symptoms such as muscle weakness and numbness are experienced.
Charcot-Marie-Tooth disease is classified into various types according to the type of gene mutation that is responsible for causing the disease.
- CMT1 involves damage to the myelin sheath can be caused by a mutation in PMP-22, P0, LITAF, EDFR or NEFL gene.
- CMT2 involves damage to the axon that can be caused by a mutation in the mitofusin-2, RAB7, GARS, NEFL, HSP27 or HSP22 gene.
- CMT3 involves severe and early onset symptoms due to damage to the myelin sheath, which is caused by a mutation in the P0 or PMP-22 gene.
- CMT4 can be caused by a mutation in GDAP1, MEMR13, MYMR2, SH3TC2, NDG1, EGR2, PRX, FDG4 or FIG4 gene.
- CMTX is caused by a mutation on the X chromosome.
As there are many different gene mutations that can lead to the presentation of CMT disease, there are several patterns of inheritance that the genes may follow. In some cases, a single copy of the gene mutation is sufficient to cause symptoms, whereas other genes require children to inherit two defected genes in order to be affected by the disease.
Some of the causative genes follow an autosomal dominant inheritance pattern. In this case, a single copy is sufficient and if the disease affects either parent, any children will have a 50% chance of inheriting the gene and being affected by CMT disease.
Other genes are inherited in an autosomal recessive pattern, which means that a child must inherit two copies of the genetic defect to experience symptoms, one from each parent. If they only one gene is inherited, they will be a carrier of the disease who does not have symptoms but have the potential to pass the condition on to any children.
Finally, X-linked inheritance refers to the inheritance of a gene mutation on the X chromosome, which is passed on from the mother to the child.
Last Updated: Mar 17, 2016