Misclassification and linkage of hereditary sensory and autonomic neuropathy type 1 as Charcot-Marie-Tooth disease, type 2B

• Published in: American journal of human genetics Vol. 59; no. 1; pp. 258 - 260
• Main Authors: Vance, J M, Speer, M C, Stajich, J M, West, S, Wolpert, C, Gaskell, P, Lennon, F, Tim, R M, Rozear, M, Othmane, K B
• Format: Journal Article
• Language: English
• Published: United States 01.07.1996
• Subjects: Charcot-Marie-Tooth Disease - classification; Charcot-Marie-Tooth Disease - diagnosis; Charcot-Marie-Tooth Disease - genetics; Chromosomes, Human, Pair 3 - genetics; Female; Genetic Linkage; Hereditary Sensory and Autonomic Neuropathies - classification; Hereditary Sensory and Autonomic Neuropathies - diagnosis; Hereditary Sensory and Autonomic Neuropathies - genetics; Humans; Letter; Lod Score; Male
• ISSN: 0002-9297; 1537-6605

Recently Kwon et al. published in the Journal their work describing linkage of a single large family with an inherited axonal neuropathy to chromosome 3, which they suggest is a second locus for Charcot-Marie-Tooth (CMT) type 2 and subsequently named "CMT2B." We think that the diagnostic classification of this family as CMT2 is incorrect, since the subjects have a severe sensory neuropathy that fits within the hereditary sensory and autonomic neuropathy (HSAN) type 1 classification of Dyck. Abnormal sensory findings in CMT2 separate it from distal spinal muscular atrophy but are a minor component of clinical symptoms in most CMT patients, as CMT is primarily a motor neuropathy. When Kwon et al. state that "all [patients] had characteristic findings on their physical examinations, including . . . evidence of foot sores that were slow to heal, or amputated limbs related to the poorly healing foot ulcers," it suggests that a different diagnosis is more appropriate. In our experience collecting data on >950 individuals in >60 CMT1, CMT2, CMTX and CMT4 families, we have not seen foot ulcers, osteomyelitis, or amputations. Ulcerations leading to osteomyelitis and amputations are usually associated with severe sensory neuropathies. HSAN type I follows an autosomal dominant pattern of inheritance, with an early adult onset associated with ulcerations, and often with lancinating pains and osteomyelitis, which may lead to amputations. Peripheral sensory symptoms are much more common than autonomic complications.