What Is CMT-DRP2?
CMT-DRP2 is a type of CMT caused by mutations in the DRP2 gene. This gene provides instructions for making dystrophin related protein 2, a component of the periaxin-DRP2-dystroglycan complex that anchors and stabilizes the outer myelin layer of Schwann cells, forming structures called Cajal bands. Mutations in the DRP2 gene disrupt this complex, leading to impaired nerve signal transmission.
CMT-DRP2 is X-linked dominant. This means the gene lives on the X chromosome, and in people with two X chromosomes (chromosomal females), a mutation in one copy of the gene causes CMT. For individuals with one X and one Y chromosome (chromosomal males), a mutation in their single copy of the gene is sufficient to cause CMT.
When a female has CMT-DRP2, each of her children has a 50% chance of inheriting her CMT. In contrast, a chromosomal male with CMT-DRP2 will pass it to all his daughters but none of his sons because males pass their X chromosome only to their daughters.
Clinical Features
The age of symptom onset in CMT-DRP2 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, consistent with an intermediate form of CMT.
CMT-DRP2 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-DRP2 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.
