CMT1H is caused by mutations in the FBLN5 gene. This gene provides instructions for producing fibulin-5, a protein involved in the structure and elasticity of connective tissue, as well as in interactions between Schwann cells and the extracellular matrix.
CMT1H is autosomal dominant, meaning that just one of the gene’s two copies needs a mutation to cause this subtype.
Clinical Features
Symptoms typically begin in adulthood (late onset), with a median age of onset in the late 30s. Both upper and lower limbs are involved, though weakness and muscle atrophy are often more pronounced in the lower limbs. Disease progression is generally slow.
CMT1H symptoms may include:
- Symptoms typically begin in adulthood
- Weakness in the feet and lower legs
- Muscle atrophy, more pronounced in the lower limbs
- Walking difficulty and gait impairment
- Reduced sensation
- Reduced deep tendon reflexes
- Unpleasant sensory sensations in the upper limbs
- Foot deformities
- Progressive involvement of the hands and forearms
- Rare features such as joint hypermobility, hyperelastic skin, or age-related macular degeneration
- Additional symptoms not listed here
Disease Course
CMT1H shows variability in severity and progression. Some individuals experience a relatively mild course, while others develop a more severe presentation. Some may experience symptoms similar to Ehlers-Danlos Syndrome (EDS). Progression is generally slow, and life expectancy is not reduced.
