Can Be Homozygous or Can Be Compound Heterozygous
CMT2B5 is caused by autosomal recessive mutations in the NEFL gene. Other mutations in this gene are associated with causing other types of CMT. CMT2B5 is also known as Autosomal Recessive CMT2E, or AR-CMT2E for short.
CMT2B5 symptoms are clinically detectable before the CMTer is 2 years old. The early symptoms are hypotonia (decreased muscle tone and strength that results in floppiness, sometimes referred to as “floppy baby”) and delayed motor milestones. A CMTer who has CMT2B5 will experience progression to profound distal (points farthest from the center of the body) and proximal (points closest to the center of the body) weakness and sensory loss throughout childhood. Sensory responses on nerve conduction studies will disappear in childhood, and conduction velocities will slow to that of a demyelinating CMT (~20 meters/sec.).
Despite CMT2B5 being an axonal CMT, scientists believe that the nerve conduction velocities exhibited in CMT2B5, although they are consistent with a demyelinating CMT (<38 meters/sec.), occur because myelinated axons fail to develop in CMT2B5. Healthy myelin is required for efficient signal transmission. Damaged myelin results in slowed conduction velocities.