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.
Graf
W D
WD
Department of Pediatrics, University of Washington School of Medicine, Seattle, USA.
Chance
P F
PF
Lensch
M W
MW
Eng
L J
LJ
Lipe
H P
HP
Bird
T D
TD
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*
D014750:Vincristine; D004247:DNA