Skin Biopsy Findings in Patients With CMT1A: Baseline Data From the CLN-PXT3003-01 Study Provide New Insights Into the Pathophysiology of the Disorder

• Published in: Journal of neuropathology and experimental neurology 2018-04, Vol.77 (4), p.274-281
• Main Authors: Duchesne, Mathilde, Danigo, Aurore, Richard, Laurence, Vallat, Jean-Michel, Attarian, Shahram, Gonnaud, Pierre-Marie, Lacour, Arnaud, Péréon, Yann, Stojkovic, Tania, Nave, Klaus-Armin, Bertrand, Viviane, Nabirotchkin, Serguei, Cohen, Daniel, Demiot, Claire, Magy, Laurent
• Format: Article
• Language: English
• Subjects: Adult; Anopheles; Biopsy; Charcot-Marie-Tooth disease; Charcot-Marie-Tooth Disease - genetics; Charcot-Marie-Tooth Disease - pathology; Charcot-Marie-Tooth Disease - physiopathology; Epstein-Barr virus; Female; Genes; Humans; Male; Medical research; Middle Aged; Myelin Proteins - genetics; Myelin Proteins - metabolism; Myelin Sheath - metabolism; Myelin Sheath - pathology; Nerve Fibers - pathology; Nerve Fibers - physiology; Neural Conduction - physiology; Severity of Illness Index; Skin; Skin - pathology; Visual Analog Scale
• ISSN: 0022-3069; 1554-6578
• DOI: 10.1093/jnen/nly001

Abstract Charcot-Marie-Tooth disease type 1A (CMT1A), the most common form of Charcot-Marie-Tooth diseases, is a demyelinating neuropathy caused by a deletion encompassing the gene coding for PMP22, a myelin protein of the peripheral nervous system. Although myelinated fibers are mostly involved in CMT1A, some patients experience neuropathic pain. We thus investigated whether unmyelinated fibers are lost in CMT1A. Skin biopsies were taken from the distal portion of the leg of 80 patients with CMT1A as part of the PXT30003-01 study and processed for quantification of intraepidermal nerve fiber density (IENFD). Mean IENFD was significantly lower in CMT1A patients than in healthy controls. Although the data were highly dispersed, IENFD tended to decrease with age and was higher overall in female patients and controls than male patients and controls. This study shows that small nerve fibers are affected in CMT1A and that this correlates with pin sensitivity. The density of epidermal Langerhans cells (LCs) was also significantly reduced in CMT1A patients, suggesting the involvement of LCs in neuropathic pain processes. These findings raise several questions concerning the interactions of Schwann cells and LCs with unmyelinated fibers in CMT1A. Moreover, they suggest that factors other than PMP22 gene dosage are involved in small fiber pathology in CMT1A.