CMTX3 is caused by a translocation mutation between 8q24.3 and Xq27.1. A translocation mutation is a type of genetic mutation in which segments of DNA have swapped places, or a segment of genetic material is found where it is not expected to be. In the case of CMTX3, genetic material normally found on chromosome 8 (8q24.3) is inserted into the X chromosome (at Xq27.1).
CMTX3 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 the related disease. For individuals with one X and one Y chromosome (chromosomal males), a mutation in their single copy of the gene is sufficient. In the case of CMTX3, rather than a single gene, a segment of chromosome 8 containing many genes (8q24.3) has been relocated to the X chromosome (Xq27.1).
Clinical Features
CMTX3 symptoms begin by the early teens. They typically begin in the lower extremities and progress over time to involve the upper limbs. Nerve conduction studies usually show slowed conduction velocities, consistent with a demyelinating form of CMT.
CMTX3 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
- Additional symptoms not listed here
Disease Course
CMTX3 shows wide variability in severity and progression. Some individuals are mildly affected, while others develop a more severe disease. Onset is by the early teens, but disease progression is generally slow, and life expectancy is not reduced.
