Which nerve biopsy findings are characteristic of Charcot-Marie-Tooth (CMT) disease type 1A?

Updated: Feb 19, 2019
  • Author: Francisco de Assis Aquino Gondim, MD, MSc, PhD, FAAN; Chief Editor: Nicholas Lorenzo, MD, MHA, CPE  more...
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Answer

Light microscopy of sural nerve biopsies from patients with a PMP22 gene region duplication reveal normal epineurium and perineurium; increased fascicular area, endoneurial collagen, and numbers of Schwann cell nuclei; and loss of large myelinated fibers that correlates with age and clinical severity. Small fibers resulting from axonal degeneration and regeneration are increased. A variable degree of granular degeneration of the myelin sheath is present. Onion bulbs are found around myelinated internodes, demyelinated internodes, or former sites of demyelinated fibers. Vacuolated fibroblasts may be observed in advanced cases. PMP22 expression in nerve biopsies is increased. Most teased fibers are abnormal with widespread segmental demyelination and frequent paranodal loss of myelin. Internode length is decreased and variable with numerous short internodes.

Axonal changes are usually mild, except for attenuation of axons of intermediate- and large-diameter myelinated fibers. The mean g ratio (axon diameter–to–fiber diameter) is low, despite the presence of demyelinated fibers, indicating an above-normal thickness of myelin sheaths (ie, hypermyelination). In contradistinction to PMP22 duplication, patients with PMP22 missense mutations who present with CMT1A or DSS have a high g ratio, which is indicative of hypomyelination and resembles Trembler-J and Trembler mice. Nerve biopsies from infants already show myelinated fiber loss with increase of the total transverse fascicular area. Onion bulbs are infrequent in the first years. During late childhood, active demyelination diminishes, demyelinated fibers become infrequent, and many onion bulbs appear.


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