CMT2CC is caused by mutations in the NEFH gene. This gene provides instructions for producing neurofilament heavy chain, a structural protein that helps maintain the shape, caliber, and stability of peripheral nerve axons. Mutations in the NEFH gene disrupt normal nerve structure, leading to impaired nerve signal transmission.
CMT2CC is autosomal dominant, meaning that just one of the gene’s two copies must have a CMT-causing mutation to cause this subtype.
Clinical Features
The age of symptom onset in CMT2CC is variable, ranging from early childhood to adulthood. Symptoms typically begin in the lower extremities and progress over time to involve the upper limbs. An earlier onset isn’t necessarily associated with a more severe disease course. Nerve conduction studies usually show normal or only mildly reduced motor conduction velocities, consistent with an axonal form of CMT.
CMT2CC symptoms may include:
- Weakness in the feet and lower legs
- Muscle atrophy
- Foot drop
- A steppage-style walking pattern
- Reduced sensation
- Reduced or absent reflexes
- Foot deformities, including high arches and hammertoes (clawed toes)
- Progressive involvement of the hands and forearms
- Difficulty with fine motor skills and manual dexterity
- Balance difficulties
- Additional symptoms not listed here
Disease Course
CMT2CC shows wide variability in severity and progression. Some individuals are mildly affected, while others develop a more severe disease. Disease progression is generally slow, and life expectancy is not reduced.
