What Is CMT-MCM3AP?
CMT-MCM3AP is a type of CMT caused by autosomal recessive mutations in the MCM3AP gene. This gene provides instructions for making GANP, a protein required for exporting messenger RNA from the cell nucleus, a process essential for normal cell function, including in peripheral nerves. Mutations in the MCM3AP gene disrupt this export process, leading to impaired nerve signal transmission.
CMT-MCM3AP 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-MCM3AP 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-MCM3AP 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-MCM3AP 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.
