What Is CMT4B2?
CMT4B2 is a type of CMT caused by mutations in the SBF2 gene. This gene provides instructions for producing SET binding factor 2, a protein involved in phosphoinositide regulation that plays an important role in maintaining normal myelin structure in peripheral nerves. Mutations in the SBF2 gene disrupt Schwann cell function and impair peripheral nerve myelin maintenance, leading to slowed nerve signal transmission.
CMT4B2 is autosomal recessive, meaning that both of the gene’s copies must have a CMT-causing mutation to cause this subtype.
Clinical Features
Symptom onset in CMT4B2 typically occurs by the mid-teens, beginning in the lower limbs and progressing to the upper body. Nerve conduction studies show slowed conduction velocities and somewhat reduced amplitudes, consistent with a demyelinating form of CMT. CMT4B2 often includes glaucoma and severe sensory neuropathy.
CMT4B2 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
- Glaucoma
- Kyphoscoliosis (kyphosis + scoliosis)
- Balance difficulties
- Additional symptoms not listed here
Disease Course
CMT4B2 shows wide variability in severity and progression. Some individuals remain mildly affected, while others are more severely affected. Even within the same family, disease progression and severity can differ substantially. Progression is generally slow, and life expectancy is not reduced.
