title: Severe vincristine neuropathy in Charcot-Marie-Tooth disease type 1A.
abstract: 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.
authors.affiliation: Department of Pediatrics, University of Washington School of Medicine, Seattle, USA.
authors.forename: W D
authors.initials: WD
authors.lastname: Graf
authors.forename: P F
authors.initials: PF
authors.lastname: Chance
authors.forename: M W
authors.initials: MW
authors.lastname: Lensch
authors.forename: L J
authors.initials: LJ
authors.lastname: Eng
authors.forename: H P
authors.initials: HP
authors.lastname: Lipe
authors.forename: T D
authors.initials: TD
authors.lastname: Bird
mesh_terms: D000293:Adolescent; D000328:Adult; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000503:physiopathology*; D002648:Child; D002886:Chromosomes, Human, Pair 17; D004247:DNA / Q000235:genetics; D004198:Disease Susceptibility; D004594:Electrophysiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000175:diagnosis; D010375:Pedigree; D011247:Pregnancy; D012189:Retrospective Studies; D014750:Vincristine / Q000009:adverse effects*
chemical_list: D014750:Vincristine; D004247:DNA