What Is CMT2B4?
CMT2B4 is a type of CMT 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.
CMT2B4 is autosomal recessive, meaning that both of the gene’s copies must have a CMT-causing mutation to cause this subtype.
Clinical Features
Symptom onset in CMT2B4 is typically before age 3 and causes profound proximal and distal weakness. Some may be unable to walk. Breathing may be severely affected, necessitating mechanical ventilation. Sensory nerve responses are absent, and motor nerve responses show variable degrees of slowing. consistent with an axonal form of CMT.
CMT2B4 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
- Severe respiratory impairment (for some patients)
- Balance difficulties
- Additional symptoms not listed here
Disease Course
CMT2B4 is typically a severe disease with an early onset. Some may never be able to walk, and breathing my be significantly affected. Although severe, disease progression is generally slow. Life expectancy may be reduced if breathing is not appropriately monitored and treated.
