CMTX2 is caused by mutations in the X chromosome at Xp22.2, but the exact gene is not yet known.
CMTX2 is X-linked recessive. This means the gene lives on the X chromosome, and in people with two X chromosomes (chromosomal females), a mutation in both copies of the gene is needed to cause CMTX2. For individuals with one X and one Y chromosome (chromosomal males), a mutation in their single copy of the gene is sufficient to cause CMTX2.
Clinical Features
Symptom onset of CMTX2 is in early infancy. 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 intermediate form of CMT. Motor development delay and cognitive impairment have been reported in some. CMTX2 should not be confused with CMT2X. CMT2X is a different CMT subtype that is caused by autosomal recessive mutations in the SPG11 gene.
CMTX2 symptoms may include:
- Weakness in the feet and lower legs
- Muscle atrophy
- Foot drop
- A steppage-style walking pattern
- Reduced sensation
- Reduced or absent reflexes
- Foot deformities, including high arches and hammertoes (clawed toes)
- Progressive involvement of the hands and forearms
- Difficulty with fine motor skills and manual dexterity
- Balance difficulties
- Cognitive impairment (some patients)
- Additional symptoms not listed here
Disease Course
CMTX2 shows wide variability in severity and progression. Some individuals are mildly affected, while others develop a more severe disease. Onset is in early infancy, but disease progression is generally slow, and life expectancy is not reduced.
