Charcot-Marie-Tooth disease: insights from skin biopsy

Inherited neuropathies, collectively known as Charcot-Marie-Tooth disease (CMT), are a group of genetically and phenotypically heterogeneous peripheral neuropathies associated with mutations or copy number variations in over 80 distinct genes. The advent of genetic testing has made sural nerve biopsy unnecessary for diagnosing most cases of CMT, particularly because the technique is somewhat invasive. Unfortunately, this has led to an inability to evaluate morphological effects by the various mutations on human nerves. Since animal models do not always faithfully reproduce human pathology the lack of human nerve tissue has limited investigations into pathogenic mechanisms of CMT. Skin biopsies increasingly offer a minimally invasive approach to overcome this problem. The aim of our project was to study the cutaneous innervation of patients with different subtypes of CMT and investigate the pathomechanisms underlying each form. We provided additional evidence that morphological data from minimally invasive skin biopsies offer similar information to that provided by sural nerve biopsies by identifying abnormalities in myelin or axons resulting from mutations in CMT causing genes. The morphological abnormalities we discussed provide interesting insights into potential pathomechanisms of axonal and demyelinating CMT.