CMT2Q is caused by mutations in the DHTKD1 gene. This gene provides instructions for producing dehydrogenase E1 and transketolase domain–containing protein 1, an enzyme involved in mitochondrial energy metabolism. Mutations in the DHTKD1 gene disrupt normal mitochondrial function in peripheral nerve cells, leading to impaired axonal function and nerve signal transmission.
CMT2Q autosomal dominant, meaning that just one of the gene’s two copies needs a mutation to cause this subtype.
Clinical Features
CMT2Q symptom onset is variable, ranging from early childhood to late 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.
CMT2Q 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
- Muscle biopsy shows:
- Small, angulated muscle fibers
- Sarcomere disappearance
- Disorganized myofilaments
- Mitochondrial vacuolization
- Additional symptoms not listed here
Disease Course
CMT2Q 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.
