CMT1E is caused by mutations in the PMP22 gene. Unlike CMT1A, which results from an extra copy of this gene, CMT1E is associated with point mutations. A point mutation is one that occurs within the gene rather than there being an extra copy or a missing copy. These mutations disrupt the normal structure and function of peripheral nerve myelin, leading to slowed nerve signal transmission.
CMT1E is autosomal dominant, meaning that just one of the gene’s two copies needs a mutation to cause this subtype.
Clinical Features
First symptoms typically appear in the lower extremities, with onset usually occurring in childhood. As with other demyelinating forms of CMT, changes in the peripheral nerves can be detected through nerve conduction studies, sometimes before symptoms are noticeable. Nerve conduction in CMT1E is very slow (<10 m/s), reflecting involvement of peripheral nerve myelin. Hearing loss, sometimes from an early age, is a common symptom in CMT1E.
CMT1E symptoms may include:
- First symptoms typically appear in the lower extremities
- Symptoms typically begin in childhood
- Weakness in the feet and lower legs
- Muscle atrophy
- Foot drop
- A steppage-style walking pattern
- Poor balance
- Reduced sensation
- Reduced or absent reflexes
- Foot deformities, including high arches, and hammertoes (clawed toes)
- Clawing of the fingers
- Sensorineural hearing loss
- Progressive involvement of the hands and forearms
- Additional symptoms not listed here
Disease Course
CMT1E 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.
