CMT2B5 is caused by mutations in the NEFL gene. This gene provides instructions for making neurofilament light chain, a structural protein that helps maintain the normal structure and function of peripheral nerve axons. Mutations in the NEFL gene disrupt normal nerve structure, leading to impaired nerve signal transmission.
CMT2B5 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 CMT2B5 typically occurs in early childhood, often before age 2. Early signs may include hypotonia and delayed motor milestones. Weakness and sensory loss progress through childhood and can become severe, affecting both distal and proximal muscles. Some individuals may develop significant functional impairment.
Nerve conduction studies show absent sensory responses and slowed motor responses, sometimes reaching values within the demyelinating range. However, this reflects abnormal axonal development rather than a primary demyelinating process, so CMT2B5 is classified as an axonal type of CMT.
CMT2B5 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
CMT2B5 is typically an early-onset and severe form of CMT. Symptoms often begin in infancy or early childhood and can lead to significant weakness and sensory loss over time. Although severe, disease progression is generally slow, and life expectancy is not affected.
