What Is CMT2B3?
CMT2B3 is a type of CMT caused by mutations in the GDAP1 gene. This gene provides instructions for producing ganglioside-induced differentiation-associated protein 1, a protein involved in mitochondrial dynamics and cellular stress responses in peripheral nerves. Mutations in the GDAP1 gene disrupt normal mitochondrial function in the peripheral nerves, leading to impaired nerve signal transmission.
CMT2B3 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 CMT2B3 is typically before age 2 and causes severe proximal and distal weakness. Some may be unable to walk and may have vocal cord paresis (muscle weakness caused by nerve impairment). Sensory nerve responses are absent, and motor nerve responses show variable degrees of slowing. consistent with an axonal form of CMT.
CMT2B3 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
- Weak voice (some patients)
- 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
CMT2B3 is typically a severe disease with an early onset. Some may never be able to walk, while others may depend on assistive devices for mobility. Although severe, disease progression is generally slow, and life expectancy is not reduced.
