What Is CMT4C?
CMT4C is a type of CMT caused by mutations in the SH3TC2 gene. This gene provides instructions for producing SH3 domain and tetratricopeptide repeat–containing protein 2, a protein that plays an important role in Schwann cell function and maintenance of peripheral nerve myelin. Mutations in the SH3TC2 gene disrupt normal myelin organization and Schwann cell processes, leading to impaired nerve signal transmission.
CMT4C 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 CMT4C is typically by the teens, but later onset in the twenties and thirties has been reported. Symptoms usually begin in the lower limbs and progress to the upper body. Progression to severe disability can be rapid. Nerve conduction studies usually show slowed conduction velocities and somewhat reduced amplitudes, consistent with a demyelinating form of CMT.
CMT4C 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
- Scoliosis (often early onset and severe)
- Motor development delay
- Cranial nerve involvement
- Nystagmus and abnormal pupillary responses
- Tongue weakness and atrophy (some patients report tongue fasciculations)
- Additional symptoms not listed here
Disease Course
CMT4C shows wide variability in severity and progression. Some individuals are mildly affected, while others develop a more severe disease. Some patients may become wheelchair-dependent at a young age. Disease progression can be rapid but is generally slow, and life expectancy is not reduced.
