What Is CMT1G?
CMT1G is a type of CMT caused by mutations in the PMP2 gene. This gene plays a role in lipid binding and the structure of myelin in peripheral nerves. Mutations in the PMP2 gene disrupt the normal organization of peripheral nerve myelin, leading to impaired nerve signal transmission.
CMT1G is autosomal dominant, meaning that just one of the gene’s two copies needs a mutation to cause this subtype.
Clinical Features
Symptoms typically begin in the first or second decade of life. The lower limbs are more affected than the upper limbs, particularly early in the disease course. Nerve conduction in CMT1G is slowed, reflecting involvement of peripheral nerve myelin. Disease progression is generally slow.
CMT1G symptoms may include:
- First symptoms typically appear in the lower extremities
- Symptoms typically begin in adolescence
- Weakness in the feet and lower legs
- Muscle atrophy
- Difficulty walking
- A steppage-style walking pattern
- Reduced or absent reflexes, particularly in the lower limbs
- Foot deformities, including high arches and hammertoes (clawed toes)
- Progressive involvement of the hands and forearms
- Additional symptoms not listed here
Disease Course
CMT1G shows variability in severity and progression. Some individuals experience a relatively mild course, while others develop a more severe presentation. Progression is generally slow, and life expectancy is not reduced.
