What Is CMT2O?
CMT2O is a type of CMT caused by mutations in the DYNC1H1 gene. This gene provides instructions for producing dynein cytoplasmic 1 heavy chain 1, a motor protein involved in intracellular transport along axons, including retrograde transport essential for neuron function. Mutations in the DYNC1H1 gene disrupt normal axonal transport processes, leading to impaired axonal function and nerve signal transmission.
CMT2O is autosomal dominant, meaning that just one of the gene’s two copies needs a mutation to cause this subtype.
Clinical Features
CMT2O symptom onset is in early childhood, typically beginning in the lower extremities and progressing over time to involve the upper limbs. Motor development delays are common. Nerve conduction studies usually show somewhat slowed conduction velocities and reduced amplitudes, consistent with an axonal form of CMT.
CMT2O symptoms may include:
- Weakness in the feet and lower legs
- Muscle atrophy
- Foot drop
- A steppage-style walking pattern
- Motor development delay
- 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
CMT2O 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.
