What Is CMT2N?
CMT2N is a type of CMT caused by mutations in the AARS1 gene. This gene provides instructions for producing alanyl-tRNA synthetase, an enzyme involved in protein synthesis that attaches alanine to its cognate transfer RNA. Mutations in the AARS1 gene impair normal cellular function in peripheral nerve cells, leading to axonal dysfunction and impaired nerve signal transmission.
CMT2N 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
The age of symptom onset in CMT2N is variable, ranging from early childhood to adulthood. 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. Severe sensorineural hearing loss has been reported.
CMT2N 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
- Balance difficulties
- Additional symptoms not listed here
Disease Course
CMT2N 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.
