What Is CMT2R?
CMT2R is a type of CMT caused by mutations in the TRIM2 gene. This gene provides instructions for producing tripartite motif–containing protein 2, an E3 ubiquitin ligase involved in protein turnover and maintenance of axonal integrity. Mutations in the TRIM2 gene disrupt normal protein regulation in peripheral nerve cells, leading to impaired axonal function and nerve signal transmission.
CMT2R is autosomal recessive, meaning both copies of the gene need a mutation to cause this subtype.
Clinical Features
CMT2R symptom onset is in early childhood, typically beginning in the lower extremities and progressing over time to involve the upper limbs. Motor development delays are common. Nerve conduction studies usually show somewhat slowed conduction velocities and reduced amplitudes, consistent with an axonal form of CMT.
CMT2R symptoms may include:
- Weakness in the feet and lower legs
- Muscle atrophy
- Foot drop
- A steppage-style walking pattern
- Motor development delay
- 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 cord paralysis
- Tracheomalacia (weak and collapsing trachea)
- Breathing muscle weakness
- Additional symptoms not listed here
Disease Course
CMT2R 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.
