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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Severe vincristine neuropathy in Charcot-Marie-Tooth disease type 1A.

BACKGROUND. A general predisposition for vincristine-related neuropathy has been observed in persons with a family history of hereditary neuropathies. METHODS. In a retrospective case series, we investigated the possible association between the DNA rearrangement found in patients with Charcot-Marie-Tooth Disease Type 1A (CMT1A) and susceptibility to the neurotoxicity of vincristine. In selected patients and family members, we performed electrodiagnostic studies and analyzed DNA samples for 17p11.1-12 duplication associated with CMT1A. RESULTS. We describe three families with autosomal dominant CMT1, among whom a family member with a neoplastic disease suffered rapid onset, severe neuropathy after receiving initial doses of vincristine as a part of a routine chemotherapy protocol. All three families had at least one affected family member with 17p11.2-12 duplication. CONCLUSIONS. These cases show that 17p11.2-12 duplication predisposes patients to severe neurotoxicity from vincristine and that this drug should be avoided with patients with CMT1A. It is therefore essential to obtain a detailed family history for all oncology patients to screen for possible hereditary neuropathies. In patients with unexplained or preexisting familial neuropathy, testing for 17p11.2-12 duplication should be carried out prior to initiating vincristine therapy. Patients with other hereditary neuropathies may also be at risk for severe neurotoxic reactions.[1]


  1. Severe vincristine neuropathy in Charcot-Marie-Tooth disease type 1A. Graf, W.D., Chance, P.F., Lensch, M.W., Eng, L.J., Lipe, H.P., Bird, T.D. Cancer (1996) [Pubmed]
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