Charcot-Marie-Tooth syndrome
P. F. Chance and D. Pleasure
Department of Pediatrics, University of Utah Medical Center, Salt Lake City.
Charcot-Marie-Tooth syndrome (CMT) is a group of genetically determined
symmetric distal polyneuropathies. The CMT loci are known to map to
chromosome 1 (CMT1B), chromosome 17 (CMT1A), the X chromosome (CMTX), and
two additional unknown autosomes (CMT1C and CMT2). The most prevalent form
is CMT1A, an autosomal dominant demyelinative disorder caused either by a
tandem duplication in band p11.2-12 of chromosome 17 (17p11.2-12) with
trisomic expression of the peripheral myelin protein-22 (PMP-22) gene or,
less frequently, by a missense mutation of PMP-22. Missense mutations in
PMP-22 are also responsible for two forms of demyelinative polyneuropathy
in mice, trembler and trembler. Hereditary neuropathy with liability to
pressure palsies (HNPP) is an autosomal dominant disorder characterized by
recurrent focal neuropathy. In all families thus far studied, patients with
HNPP have been found to be monosomic for a segment of chromosome
17p11.2-12. The duplication in CMT1A and deletion in HNPP map to the same
region in 17p11.2-12 and are both likely to be consequences of unequal
crossing over during germ cell meiosis.
