validity of current CMT classification criteria/new diagnostic strategies needed

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Editorial/Research from Neurologia. June 2004;19(5):264-271.

Different phenotypes of Charcot-Marie-Tooth disease caused by mutations

in the same gene. Are classical criteria for classification still valid?

Sevilla Mantecon T, Vilchez Padilla J; Servicio de Neurologia. Hospital

Universitario La Fe. Valencia. Espana.

Molecular genetic research is leading to the continuous discovery of new

genes and protein involved in peripheral nerves function.

Simultaneously, extended clinical, neurophysiological and pathological

research has yielded new genotype-phenotype correlation on

Charcot-Marie-Tooth disease (CMT). This has made it possible to know

that several genes can cause both demyelinating (CMT1) and axonal (CMT2)

phenotypes. Those observations have questioned the validity of some

current criteria for CMT classification and raise the need for new

strategies for diagnosis. The discovery of Schwann cell-axon interaction

is a challenge for coming years. In this review, we extensively analyzed

mutations of genes that give rise to CMT1 or CMT2 phenotypes. There are

at least three forms of genetic variability. MPZ gene mutations yield a

real allelism, that is, CMT1 or CMT phenotypes associated to specific

mutation by site or quality. GADP1 and probably NF-L gene manifest

different phenotypes but only in terms of nerve conduction velocity

(CV). Evidence is provided that indicates that CV reduction in GADP-1

neuropathy may be the result of axonal loss. Finally a third form of

variability is present in CMTX due to the degree of clinical expression

in females related with the inactivation of chromosome X.