What Is CMT2S?
CMT2S is a type of CMT caused by mutations in the IGHMBP2 gene. This gene provides instructions for producing immunoglobulin mu–binding protein 2, a helicase involved in nucleic acid processing and normal motor neuron function. Mutations in the IGHMBP2 gene disrupt essential cellular processes in peripheral nerve cells, leading to impaired axonal function and nerve signal transmission.
CMT2S is autosomal recessive, meaning both copies of the gene need a mutation to cause this subtype.
Clinical Features
CMT2S typically has an early childhood onset, beginning in the lower extremities and progressing over time to involve the upper limbs. Most who have CMT2S will become wheelchair dependent. Nerve conduction studies usually show somewhat slowed conduction velocities and reduced amplitudes, consistent with an axonal form of CMT.
CMT2S symptoms may include:
- Weakness in the feet and lower legs
- Muscle atrophy
- Foot drop
- A steppage-style walking pattern
- Motor development delay
- 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
- Breathing muscle weakness
- Additional symptoms not listed here
Disease Course
CMT2S typically has a severe disease course. Most will become wheelchair dependent. Breathing can be significantly affected for some patients. Although severe, disease progression is generally slow. Life expectancy may be reduced if breathing is not appropriately monitored and treated.
