What Is CMT2T?
CMT2T is a type of CMT caused by mutations in the MME gene. This gene provides instructions for producing membrane metalloendopeptidase, an enzyme involved in the breakdown of neuropeptides and regulation of signaling at the cell surface. Mutations in the MME gene disrupt normal peptide processing in peripheral nerve cells, leading to impaired axonal function and nerve signal transmission.
CMT2T can be either autosomal dominant or autosomal recessive, meaning that sometimes it’s just one of the gene’s two copies with a CMT-causing mutation, and sometimes it’s both copies.
Clinical Features
CMT2T is a late-onset subtype with symptoms typically beginning in the thirties and later. 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.
CMT2T 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
CMT2T shows wide variability in severity and progression. Some individuals are mildly affected, while others develop a more severe disease. Patients with a single, pathogenic heterozygous MME gene mutation typically have a later onset. Disease progression is generally slow, and life expectancy is not reduced.
