What Is CMT1B?
CMT1B is a type of CMT caused by mutations in the MPZ gene. This gene provides instructions for making myelin protein zero, a crucial structural protein essential for the formation of normal peripheral nerve myelin. Mutations in the MPZ gene disrupt the formation and stability of myelin, leading to slowed nerve signal transmission.
CMT1B is autosomal dominant, meaning that just one of the gene’s two copies needs a mutation to cause this subtype.
Clinical Features
Symptoms often begin in childhood or adolescence, although changes in the peripheral nerves can be detected earlier through nerve conduction studies, sometimes before symptoms are noticeable. Symptom onset can also occur much later. Nerve conduction in CMT1B is typically slowed, reflecting involvement of peripheral nerve myelin.
CMT1B symptoms may include:
- Weakness in the feet and lower legs
- Muscle atrophy
- Foot drop
- A steppage-style walking pattern
- Foot deformities, including high arches and hammertoes (clawed toes)
- Reduced sensation
- Muscle cramping
- Reduced or absent reflexes
- Enlarged peripheral nerves (hypertrophic nerves)
- Clawing of the fingers
- Spinal curvature, including scoliosis or kyphoscoliosis
- Abnormal pupil responses, including pupils that remain dilated or respond poorly to light
- Additional symptoms not listed here
Disease Course
CMT1B shows wide variability in severity and progression. Some individuals remain mildly affected, while others develop more severe weakness and functional impairment. Even within the same family, disease severity and progression can differ substantially. Progression is generally slow, and life expectancy is not reduced.
Why Is the MPZ Gene Also Linked to Other CMT Subtypes?
CMT1B is one of four subtypes caused by mutations in the MPZ gene. The same gene is also associated with CMT2I, CMT2J, and dominant intermediate D (CMTDID). The diagnosis is based on nerve conduction study (NCS) results and certain clinical features at the time of diagnosis.
When NCS results show a demyelinating type of CMT, the diagnosis is typically CMT1B. When NCS results show an axonal type of CMT, the diagnosis is typically CMT2I. If axonal and includes pupil abnormalities (pupils that remain dilated or respond poorly to light) with sensorineural hearing loss, CMT2J is the diagnosis. When NCS results fall between demyelinating and axonal CMT, the diagnosis is dominant intermediate D (CMTDID).
All CMT subtypes lead to eventual axonal degeneration. Over time, nerve conduction results that begin as demyelinating may shift toward a more axonal pattern. In some cases, this can lead a clinician to reference both CMT1 (demyelinating) and CMT2 (axonal). This does not mean that someone has two different types of CMT or that CMT is changing types. Instead, the label reflects the clinical complexity that MPZ-related CMT often exhibits.
