CMT2K

CMT2K is caused by autosomal dominant and autosomal recessive mutations in the GDAP1 gene.

CMT2K symptoms usually start to occur in early childhood, and often in infancy. The first signs of CMT2K are usually hypotonia (floppy muscles, and sometimes referred to as “floppy baby”) and delayed motor development milestones—sitting up without assistance, crawling, etc.

A CMTer who has CMT2K will usually experience significant difficulties with walking, significant foot deformities, significant kyphoscoliosis (kyphosis is a condition that creates a “hunch back;” scoliosis is a condition in which there is a side-to-side “S” curve of the spine; and the two occurring together is referred to as kyphoscoliosis), significant sensory loss in the lower legs, feet, and hands; and the CMTer will usually experience hand contractures (clawed hands) at a relatively young age.

On nerve conduction study, CMTers who have CMT2K will usually exhibit nerve conduction velocities that are preserved at normal (~50 meters/sec) with reduced action potential amplitudes. This is consistent with an axonal CMT.

In 2015, scientists (Pla-Martin et al., (2015)) identified an autosomal dominant mutation in the JPH1 gene (located at the same chromosomal address as the GDAP1 gene: 8q21.11) that they believe serves as a gene modifier to CMT2K. CMTers who have CMT2K and who also have the autosomal dominant mutation in the JPH1 gene tend to have a far more severe disease course than CMT2Kers who do not have this JPH1 mutation.