There are many different types of Charcot-Marie-Tooth disease (CMT). While the different CMT subtypes share similar symptoms, the underlying cause of each type of CMT varies. Understanding these causes is critically important for developing and administering treatments.
CMT1 is a form of CMT that is inherited with autosomal dominance. This means the disease occurs with at least one copy of the disease-causing gene, and affected individuals usually also have one normal copy of the gene on a pair of chromosomes that do not affect gender. In CMT1, the part of the nervous system that is dysfunctional is called myelin. Myelin is a wrapping around the parts of the nerves that facilitate rapid electrical signals to other parts of the body. When it is damaged, like in CMT1, that signaling can slow, weaken and become uncoordinated. The slowing of electrical signals and loss of coordinated signaling is what leads to muscle weakness.
Symptoms of CMT1
The first symptom of CMT1 is usually muscle weakness in the feet. This presents as hammertoes and pes cavus (high arch), which are caused by the small muscles in the feet deteriorating. Additionally, people with CMT1 often have a loss of sensation accompanying this weakness. Their symptoms affect both motor and sensory function because the myelin that is meant to insulate nerves is damaged, impacting communication with the musculature and the sensory organs in the skin. CMT1 is a progressive disorder, meaning the symptoms will worsen over time, but this progression is usually slow. Eventually, the weakness and loss of sensation will work its way closer to the torso and begin affecting the arms and hands. As the disease worsens, people with CMT1 can expect a loss of coordination or balance due to a loss of a particular kind of sensory ability called proprioception. Proprioception is the ability to sense where your body (and limbs) are in space. Loss of proprioception causes uncoordinated movements and imbalance.
Causes of CMT1
Axons are what carry signals to the nerves; the nerves that move your toes or fingers reach all the way from your spinal cord to your fingers and toes. Axons are covered by an insulating material called myelin. Myelin is produced by cells called Schwann Cells, and the myelin wraps around the axon.
CMT1 has been linked to several different genetic causes. Most of these are specific to Schwann Cells that produce myelin in the peripheral nervous system. The myelin produced by these cells is essential for normal function, therefore disruptions in the Schwann Cells and their ability to produce myelin frequently result in CMT1 disease symptoms. Because the defects caused by these mutations are unique to these specific cells, improving myelin function a strong target for designing therapies.
Need an even simpler way to understand CMT genetics? Watch this quick 5-minute video from scientific expert Dr. Grace Pavlath.
When genetic links are discovered, they are added to the CMT type name as an uppercase letter as a genetic identifier. For example, CMT1A, the most common form of CMT. There are seven different genetic types of CMT1:
- CMT1A: A duplication of the PMP22 gene
- CMT1B: Mutations within the MPZ gene
- CMT1C: Mutations within the gene known as either LITAF or SIMPLE
- CMT1D: Mutations within the EGR2 gene
- CMT1E: Mutations within the PMP22 gene
- CMT1F: Mutations within the NEFL gene
- CMT1G: Mutations within the PMP2 gene
As more genes are identified, the types will expand. And soon, scientists and researchers will primarily use the gene mutation to identify the problem rather than the subtype.
Treatments for CMT1
While no treatments or cures currently exist for CMT, the science to change that does. The CMT Research Foundation is currently funding cutting-edge research solely focused on drug development, including projects to advance treatments for CMT1.
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