What Is CMT2JJ?
CMT2JJ is a type of CMT caused by mutations in the BAG3 gene. This gene provides instructions for producing BCL2-associated athanogene 3, a co-chaperone protein involved in protein quality control and cellular stress response pathways, including autophagy. Mutations in the BAG3 gene disrupt normal maintenance of cellular proteins in peripheral nerve cells, leading to impaired axonal function and nerve signal transmission.
CMT2JJ is autosomal dominant, meaning that just one of the gene’s two copies must have a CMT-causing mutation to cause this subtype.
Clinical Features
CMT2JJ symptom onset is usually in adulthood, but may start in childhood or adolescence. Symptoms typically begin in the lower extremities and progress over time to involve the upper limbs. An earlier onset isn’t necessarily associated with a more severe disease course. Nerve conduction studies usually show somewhat slowed conduction velocities and reduced amplitudes, consistent with an axonal form of CMT.
CMT2JJ 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
- Breathing muscle weakness (in some patients)
- Balance difficulties
- Additional symptoms not listed here
Disease Course
CMT2JJ 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.
