What Is CMTDIC?
CMTDIC is a type of CMT caused by mutations in the YARS1 gene. This gene provides instructions for making tyrosyl-tRNA synthetase (TyrRS), an enzyme that attaches the amino acid tyrosine to its cognate (corresponding) transfer RNA during protein synthesis. Mutations in the YARS1 gene are thought to cause nerve damage through a toxic gain-of-function mechanism, where the malfunctioning enzyme acquires harmful properties that progressively damage peripheral nerve axons.
CMTDIC is autosomal dominant, meaning that just one of the gene’s two copies needs a mutation to cause this subtype.
Clinical Features
CMTDID symptom onset is variable, ranging from early childhood to adulthood. Nerve conduction studies usually show conduction velocities and reduced amplitudes that fall between a demyelinating and an axonal form of CMT.
CMTDID symptoms may include:
- Weakness in the feet and lower legs
- Muscle atrophy
- Foot drop
- A steppage-style walking pattern
- Foot deformities, including high arches and hammertoes (clawed toes)
- Reduced sensation
- Muscle cramping
- Reduced or absent reflexes
- Enlarged peripheral nerves (hypertrophic nerves)
- Clawing of the fingers
- Additional symptoms not listed here
Disease Course
CMTDIC shows wide variability in severity and progression. Some individuals remain mildly affected, while others develop a more severe disease. Progression is generally slow, and life expectancy is not reduced.
