CMT2L is caused by mutations in the HSPB8 gene. This gene provides instructions for producing heat shock protein beta-8, a molecular chaperone involved in protein quality control and cellular stress response. Mutations in the HSPB8 gene disrupt normal maintenance of proteins in peripheral nerve cells, leading to impaired axonal function and 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
CMT2L symptoms usually begin in the teens through early thirties. 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. Sensory nerve responses may be absent.
CMT2L 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
CMT2L 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.
