CMT2A2B is caused by mutations in the MFN2 gene. This gene provides instructions for producing mitofusin-2, a protein crucial for the normal fusion and transport of mitochondria within nerve cells. Mutations in the MFN2 gene disrupt mitochondrial function in peripheral nerves.
CMT2A2B is autosomal recessive, meaning that both of the gene’s copies must have a CMT-causing mutation to cause this subtype.
Clinical Features
The age of symptom onset in CMT2A2B 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 is often associated with a more severe disease course over time. Nerve conduction studies usually show normal or only mildly reduced motor conduction velocities, consistent with an axonal form of CMT.
CMT2A2B 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
CMT2A2B shows wide variability in severity and progression. Some individuals are mildly affected, while others develop a more severe disease, particularly when symptoms begin early in life. Disease progression is generally slow, and life expectancy is not reduced.
