CMT1D is caused by mutations in the EGR2 gene. This gene plays a key role in regulating the development and maintenance of peripheral nerve myelin. Mutations in the EGR2 gene disrupt normal myelin formation, leading to slowed nerve signal transmission.
CMT1D is autosomal dominant, meaning that just one of the gene’s two copies needs a mutation to cause this subtype.
Clinical Features
First symptoms typically appear in the lower extremities. Symptoms typically begin by the mid-teens, though the exact age of onset can vary. Changes in the peripheral nerves can be detected through nerve conduction studies. Nerve conduction in CMT1D is slowed, reflecting involvement of peripheral nerve myelin.
CMT1D symptoms may include:
- First symptoms typically appear in the lower extremities
- Symptoms typically begin by the mid-teens
- Weakness in the feet and lower legs
- Muscle atrophy
- Foot drop
- A steppage-style walking pattern
- Foot deformities, including high arches and hammer toes (clawed toes)
- Progressive involvement of the hands and forearms
- Additional symptoms not listed here
Disease Course
CMT1D shows wide variability in severity and progression. Some individuals remain mildly affected, while others develop more severe weakness and functional impairment. Even within the same family, disease severity and progression can differ substantially. Progression is generally slow, and life expectancy is not reduced.
