What Is CMT-DGAT2?
CMT-DGAT2 is a type of CMT caused by autosomal dominant mutations in the DGAT2 gene. This gene provides instructions for making an enzyme that catalyzes the final step of triglyceride synthesis, converting diacylglycerol and fatty acids into triglycerides for storage as lipid droplets. Mutations in the DGAT2 gene disrupt normal lipid metabolism in peripheral nerve cells, leading to impaired nerve signal transmission.
CMT-DGAT2 is autosomal dominant, meaning that just one of the gene’s two copies needs a mutation to cause this subtype.
Clinical Features
The age of symptom onset in CMT-DGAT2 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 and reduced amplitudes, consistent with an axonal form of CMT.
CMT-DGAT2 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-DGAT2 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.
