CMT1J is caused by mutations in the ITPR3 gene. This gene encodes inositol 1,4,5-trisphosphate receptor type 3, a protein involved in intracellular calcium signaling that plays an important role in neuronal function. Mutations in the ITPR3 gene disrupt normal signaling pathways in peripheral nerves, leading to impaired myelin function and slowed nerve signal transmission.
CMT1J is autosomal dominant, meaning that just one of the gene’s two copies needs a mutation to cause this subtype.
Clinical Features
The age of symptom onset in CMT1J is variable, ranging from childhood to middle adulthood. Symptoms often begin in the lower extremities and progress gradually over time. Nerve conduction studies typically show demyelinating or intermediate-range conduction velocities, reflecting involvement of peripheral nerve myelin.
CMT1J symptoms may include:
- Symptoms may begin in childhood or adulthood
- First symptoms typically appear in the lower extremities
- Weakness in the feet and lower legs
- Muscle atrophy
- Foot drop
- Gait abnormalities
- Reduced sensation
- Reduced or absent reflexes
- Foot deformities, including high arches and hammertoes (clawed toes)
- Progressive involvement of the hands and forearms
- Additional symptoms not listed here
Disease Course
CMT1J shows variability in severity and progression. Some individuals experience a relatively mild course, while others develop a more severe presentation. Progression is generally slow, and life expectancy is not reduced.
