What Is CMT2Z?
CMT2Z is a type of CMT caused by mutations in the MORC2 gene. This gene provides instructions for producing MORC family CW-type zinc finger 2, a protein involved in chromatin remodeling and the regulation of gene expression, which is important for normal neuronal function. Mutations in the MORC2 gene disrupt cellular regulation and axonal integrity in peripheral nerves, leading to impaired nerve signal transmission.
CMT2Z is autosomal dominant, meaning that just one of the gene’s two copies must have a CMT-causing mutation to cause this subtype.
Clinical Features
The age of symptom onset in CMT2Z is variable, ranging from infancy to early adulthood. Symptoms typically begin in the lower extremities and progress over time to involve the upper limbs. An earlier onset isn’t necessarily associated with a more severe disease course. Nerve conduction studies usually show somewhat slowed conduction velocities and reduced amplitudes, consistent with an axonal form of CMT. Motor development delay and learning disabilities have been reported in some.
CMT2Z 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
- Motor development delay (some patients)
- Learning disability (some patients)
- Additional symptoms not listed here
Disease Course
CMT2Z 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.
