CMT4J is caused by mutations in the FIG4 gene. This gene provides instructions for producing a protein involved in phosphoinositide metabolism, which is essential for normal membrane trafficking and maintenance of peripheral nerve cells. Mutations in the FIG4 gene disrupt normal cellular signaling and Schwann cell function, leading to slowed nerve signal transmission.
CMT4J 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 CMT4J is typically in early childhood, but later onset in the twenties and thirties has been reported. Symptoms usually begin in the lower limbs and progress to the upper body. Progression to severe disability can be rapid. Symptoms can be accelerated by traumatic injuries. Nerve conduction studies usually show slowed conduction velocities and somewhat reduced amplitudes, consistent with a demyelinating form of CMT.
CMT4J 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
- Scoliosis (in some patients)
- Motor development delay (in some patients)
- Additional symptoms not listed here
Disease Course
CMT4J shows wide variability in severity and progression. Some individuals are mildly affected, while others develop a more severe disease. Some patients may become wheelchair-dependent at a young age. Disease progression can be rapid but is generally slow, and life expectancy is not reduced.
