What Is CMT-HINT1?
CMT-HINT1 is a type of CMT caused by autosomal recessive mutations in the HINT1 gene. This gene provides instructions for making histidine triad nucleotide-binding protein 1, an enzyme involved in nucleotide processing and cellular signaling in peripheral nerve cells. Mutations in the HINT1 gene disrupt this function, leading to impaired nerve signal transmission.
CMT-HINT1 is autosomal recessive, meaning that both copies of the gene must have a mutation to cause this subtype.
Clinical Features
The age of symptom onset in CMT-HINT1 is variable, typically in childhood or adolescence. This subtype combines a motor-predominant peripheral neuropathy with neuromyotonia, a delayed relaxation of the muscles after contraction. Nerve conduction studies usually show somewhat slowed conduction velocities and reduced amplitudes, consistent with an axonal form of CMT.
CMT-HINT1 symptoms may include:
- Weakness in the feet and lower legs
- Muscle atrophy
- Foot drop
- Neuromyotonia, with muscle stiffness and delayed relaxation
- Muscle cramping
- Reduced or absent reflexes
- Foot deformities, including high arches
- Difficulty with fine motor skills and manual dexterity
- Additional symptoms not listed here
Disease Course
CMT-HINT1 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.
