What Is CMT-LRP12?
CMT-LRP12 is a type of CMT caused by autosomal dominant CGG repeat expansions in the LRP12 gene. Unlike most CMT-causing changes, this expansion is translated into an abnormal protein that forms toxic aggregates inside nerve cells, disrupting normal nerve cell function.
CMT-LRP12 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-LRP12 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-LRP12 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-LRP12 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.
