What Is CMT-CNTNAP1?
CMT-CNTNAP1 is a type of CMT caused by autosomal recessive mutations in the CNTNAP1 gene. This gene provides instructions for making CASPR, a protein that anchors the paranodal junctions flanking the nodes of Ranvier in myelinated peripheral nerves, organizing the axon membrane into the distinct domains required for efficient nerve signal conduction. Mutations in the CNTNAP1 gene disrupt this organization, leading to impaired nerve signal transmission.
CMT-CNTNAP1 is autosomal recessive, meaning that both copies of the gene must have a mutation to cause this subtype.
Clinical Features
The age of symptom onset in CMT-CNTNAP1 is variable, ranging from childhood to adulthood. Symptoms typically begin in the lower extremities and progress over time to involve the upper limbs. Nerve conduction studies usually show somewhat slowed conduction velocities and reduced amplitudes, consistent with an axonal form of CMT.
CMT-CNTNAP1 symptoms may include:
- Weakness in the feet and lower legs
- Muscle atrophy
- Foot drop
- Reduced or absent reflexes
- Reduced sensation
- A steppage-style walking pattern
- Foot deformities, including high arches, and hammertoes (clawed toes)
- Progressive involvement of the hands and forearms
- Difficulty with fine motor skills and manual dexterity
- Additional symptoms not listed here
Disease Course
CMT-CNTNAP1 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.
