The pathology of Charcot‐Marie‐Tooth disease and related disorders

Abstract

Approximately a quarter of a century ago, the disorders originally designated as Charcot-Marie-Tooth disease and Dejerine-Sottas disease were shown by combined clinical, electrophysiological and nerve biopsy studies to be genetically complex. In pathological terms they could be broadly classified into demyelinating neuropathies and axonopathies. Advances in the molecular genetics of these disorders, particularly for those with a demyelinating basis, have recently produced substantial new insights. The identification of mutations in genes for myelin proteins has provided the opportunity for investigating the precise mechanisms of these neuropathies, including the use of spontaneous and genetically engineered animal models.

Clinical features and molecular genetics of hereditary peripheral neuropathies

“…In some cases, a visible and palpable hypertrophy of peripheral nerves, especially the great auricular nerve, can be found. Pathological examination of peripheral nerves in CMT1 shows de-and remyelination with formation of so called "onion-bulbs" [190]. Onion-bulbs are altered myelin structures generated by repeated de-and remyelination.…”

“…The peripheral nerves are not palpably enlarged. Histological characteristics are mainly axonal pathological changes with a loss of large myelinated axons and signs of regeneration with a large number of small thinly myelinated axons [190].…”

“…Electrophysiological examination usually shows prolonged distal latencies, slowing of mNCVs and conduction blocks [6, 20]. Biopsies of the sural nerve reveal characteristic focal thickenings, so called tomacula, and signs of de-and remyelination [190]. Approximately 85 % of the cases are caused by a 1.5 Mb deletion encompassing the same segment of chromosome 17p11.2 which is tandemly duplicated in CMT1A [40].…”

Erbliche Neuropathien

“…Die peripheren Nerven sind nicht verdickt. Histologisch finden sich vorwiegend axonale Veränderungen mit einem Verlust groûer myelinisierter Axone und Zeichen der Regeneration mit einer groûen Anzahl dünner myelinisierter Axone [14]. [142].…”

“…Elektrophysiologische Untersuchungen zeigen meist verlängerte distale Latenzen, Verlangsamung der motorischen NLGs und Leitungsblöcke [173,175]. Biopsien des N. suralis weisen charakteristische fokale Verdickungen (so genannte Tomacula; lateinisch: Würstchen) und Zeichen der De-und Remyelinisierung auf [14].…”