CMT1F is caused by mutations in the NEFL gene. This gene provides instructions for making neurofilament light chain, a structural protein that helps maintain the normal structure and function of peripheral nerve axons.
CMT1F is autosomal dominant, meaning that just one of the gene’s two copies needs a mutation to cause this subtype.
CMT1F is sometimes referred to as CMT1F/CMT2E and vice versa. This is because mutations in the NEFL gene cause both subtypes. When nerve conduction study (NCS) shows a demyelinating CMT, the diagnosis is CMT1F; when it shows an axonal CMT, the diagnosis is CMT2E.
Clinical Features
The first symptoms typically appear in the lower extremities, with onset usually occurring in infancy or childhood. In some individuals, early signs may include delayed motor development. Nerve conduction in CMT1F is slowed, reflecting involvement of peripheral nerve myelin. When slowed only somewhat, an axonal CMT is indicated (CMT2E). Hence, the former 1F/2E designation.
CMT1F symptoms may include:
- First symptoms typically appear in the lower extremities
- Symptoms typically begin in infancy or childhood
- Delayed motor development
- Weakness in the feet and lower legs
- Muscle atrophy
- Reduced sensation
- Reduced or absent reflexes
- Foot deformities, including high arches and hammertoes (clawed toes)
- Loss of myelinated fibers
- Irregular myelin foldings
- Clusters of axonal regeneration
- Additional symptoms not listed here
Disease Course
CMT1F shows wide variability in severity and progression. Some individuals remain mildly affected, while others develop more severe weakness and functional impairment. Even within the same family, disease severity and progression can differ substantially. Progression is generally slow, and life expectancy is not reduced.
