What Is CMT4K?
CMT4K is a type of CMT caused by mutations in the SURF1 gene. This gene provides instructions for producing a protein involved in mitochondrial energy production, specifically in the assembly of cytochrome c oxidase, an essential component of the cellular respiratory chain. Mutations in the SURF1 gene disrupt normal energy production in peripheral nerve cells, leading to impaired nerve signal transmission.
CMT4K 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 CMT4K is typically before age 10. Symptoms usually begin in the lower limbs and progress to the upper body. Periaqueductal white matter lesions have been reported, along with other white matter abnormalities, in some patients.
Nerve conduction studies usually show slowed conduction velocities and somewhat reduced amplitudes, consistent with a demyelinating form of CMT.
CMT4K 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
- Kyphoscoliosis
- Motor development delay
- Cranial nerve involvement
- Nystagmus and abnormal pupillary responses
- Periaqueductal white matter lesions (in some patients)
- Hyperintense lesions in the putamina (in some patients)
- Sensorineural hearing loss (mild, in some patients)
- Additional symptoms not listed here
Disease Course
CMT4K shows wide variability in severity and progression. Some individuals are mildly affected, while others develop a more severe disease. Disease progression is generally slow, and life expectancy is not reduced.
