What Is CMT2M?
CMT2M is a type of CMT caused by mutations in the DNM2 gene. This gene provides instructions for producing dynamin-2, a protein involved in membrane trafficking and endocytosis, which are important for normal cellular organization and nerve function. Mutations in the DNM2 gene disrupt normal intracellular transport processes in peripheral nerve cells, leading to impaired axonal function and nerve signal transmission.
CMT2M 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 CMT2M is variable, ranging from early childhood to the teens. Symptoms typically begin in the lower extremities and progress over time to involve the upper limbs. Nerve conduction studies usually show somewhat slowed conduction velocities and reduced amplitudes, consistent with an axonal form of CMT. When conduction velocity is slower (less than 38 meters/sec), the diagnosis is dominant intermediate CMT B (CMTDIB).
CMT2M 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
- Breathing muscle weakness (in some patients)
- Balance difficulties
- Additional symptoms not listed here
Disease Course
CMT2M 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.
