What Is CMT4F?
CMT4F is a type of CMT caused by mutations in the PRX gene. This gene provides instructions for producing periaxin, a protein that plays an important role in maintaining the structure and stability of the myelin sheath in peripheral nerves. Mutations in the PRX gene disrupt normal Schwann cell function and myelin maintenance, leading to impaired nerve signal transmission.
CMT4F 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 CMT4F is variable, ranging from early childhood to mid-adulthood. Symptoms usually begin in the lower limbs and progress to the upper body. Vocal fold paresis has been reported. Nerve conduction studies usually show slowed conduction velocities and somewhat reduced amplitudes, consistent with a demyelinating form of CMT.
CMT4F 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
- Vocal fold paresis (some patients)
- Motor development delay
- Additional symptoms not listed here
Disease Course
CMT4F shows wide variability in severity and progression. Some individuals are mildly affected, while others develop a more severe disease. Disease progression can be rapid but is generally slow, and life expectancy is not reduced.
