What Is CMT 1I?
CMT1I is a type of CMT caused by mutations in the POLR3B gene. This gene encodes (provides instructions for)a subunit of RNA polymerase III, which plays a crucial role in regulating the expression of genes essential for nervous system development and function.
CMT1I is autosomal dominant, meaning that just one of the gene’s two copies needs a mutation to cause this subtype.
Clinical Features
Symptoms typically begin in early childhood. In many individuals, symptoms first affect the lower extremities and later involve the upper limbs. Some individuals also show features of central nervous system involvement. Nerve conduction studies show slowed conduction velocities consistent with a demyelinating CMT.
CMT1I symptoms may include:
- Symptoms typically begin in early childhood
- First symptoms typically appear in the lower extremities
- Delayed motor development or delayed walking
- Weakness in the feet and lower legs
- Muscle atrophy
- Foot drop
- A steppage-style or unsteady walking pattern
- Reduced sensation
- Reduced or absent reflexes
- Foot deformities, including high arches and hammertoes (clawed toes)
- Clawing of the fingers
- Balance and coordination difficulties, including ataxia
- Speech difficulties, including dysarthria or delayed speech
- Tremor or abnormal movements
- Additional symptoms not listed here
Disease Course
CMT1I shows variability in severity and progression. Some individuals experience a relatively mild course, while others develop a more severe presentation. Progression is generally slow, and life expectancy is not reduced.
