CMT2F is caused by mutations in the HSPB1 gene. This gene provides instructions for producing heat shock protein beta-1, a molecular chaperone that helps protect cells from stress and supports normal protein folding. Mutations in the HSPB1 gene disrupt cellular stress responses in peripheral nerve cells, leading to axonal dysfunction and impaired nerve signal transmission.
CMT2F 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 CMT2F is variable, ranging from early childhood to the fifties. 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 somewhat slowed conduction velocities and reduced amplitudes, consistent with an axonal form of CMT.
CMT2F 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
CMT2F 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.
