What Is CMT2W?
CMT2W is a type of CMT caused by mutations in the HARS1 gene. This gene provides instructions for producing histidyl-tRNA synthetase, an enzyme involved in protein synthesis that attaches the amino acid histidine to its corresponding transfer RNA. Mutations in the HARS1 gene disrupt normal protein synthesis in peripheral nerve cells, leading to impaired axonal function and nerve signal transmission.
CMT2W 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 CMT2W 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.
CMT2W 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 (some will have very brisk patella 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
CMT2W 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.
