CMT2B1 is caused by mutations in the LMNA gene. This gene encodes (provides instructions for producing) lamin A and lamin C, proteins that play a key role in maintaining nuclear structure and cellular integrity. Mutations in the LMNA gene disrupt normal cellular function in peripheral nerves, leading to impaired nerve signal transmission.
CMT2B1 is autosomal recessive, meaning that both of the gene’s copies must have a CMT-causing mutation to cause this subtype.
Clinical Features
The age of symptom onset in CMT2B1 is variable, but usually by one’s early teens. Symptoms typically begin in the lower extremities and progress over time to involve the upper limbs. An earlier onset is often associated with a more severe disease course over time. Nerve conduction studies usually show normal or only mildly reduced motor conduction velocities, consistent with an axonal form of CMT.
CMT2B1 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
CMT2B1 shows wide variability in severity and progression. Most, however, will have a more severe disease, particularly when symptoms begin early in life. Disease progression is generally slow, and life expectancy is not reduced.
