CMT2J is caused by mutations in the MPZ gene. This gene provides instructions for making myelin protein zero, a crucial structural protein essential for the formation of normal peripheral nerve myelin. Mutations in the MPZ gene disrupt the formation and stability of myelin, leading to slowed nerve signal transmission, although signal transmission is only somewhat slowed in CMT2J.
CMT2J is autosomal dominant, meaning that just one of the gene’s two copies needs a mutation to cause this subtype.
Clinical Features
CMT2J is a late-onset subtype, with symptoms usually beginning in the thirties or later. Nerve conduction studies usually show somewhat slowed conduction velocities and reduced amplitudes, consistent with an axonal form of CMT.
CMT2J symptoms may include:
- Weakness in the feet and lower legs
- Muscle atrophy
- Foot drop
- A steppage-style walking pattern
- Foot deformities, including high arches and hammertoes (clawed toes)
- Reduced sensation
- Muscle cramping
- Reduced or absent reflexes
- Enlarged peripheral nerves (hypertrophic nerves)
- Clawing of the fingers
- Spinal curvature, including scoliosis or kyphoscoliosis
- Abnormal pupil responses, including pupils that remain dilated or respond poorly to light
- Significant hearing loss
- Additional symptoms not listed here
Disease Course
CMT2J shows wide variability in severity and progression. Some individuals remain mildly affected, while others develop a more severe disease. Progression is generally slow, and life expectancy is not reduced.
