Intermediate CharcotMarieTooth disease

10 de April de 2017

Charcot-Marie-Tooth disease (CMT) is the most common hereditary neuropathy that, according to the values of motor conduction velocity (MCV) of the median nerve (normal, ≥49 m / s), is divided into three basic patterns: i / demyelinating, CMT1 with MCV <38 m / s (average around 20 m / s); Ii / axonal, CMT2 with MCV > 38 / m / s (average around 45 m / s); And iii / intermediate, I-CMT with VCM between 25 and 45 m / s. For each CMT pattern, the inheritance may be autosomal dominant, autosomal recessive or X-linked. CMT is a very complex syndrome, particularly since the introduction of mass sequencing technology that has allowed for individualisation of mutations in more than 80 genes. Because of the relative breadth of MCV limit values, I-CMT nosology has been controversial since its original description in 1978.

A systematic review of I-CMT following the PRISMA Declaration has been carried out in collaboration between IDIVAL researchers, Miguel Server Hospital (Zaragoza) and VIB Center for Molecular Genetics (University of Antwerp, Belgium). Berciano et al, J Neurol 2017 Mar 31. doi: 10.1007 / s00415-017-8474-3). To this end, the authors have defined the limits of intermediate conduction considering the amplitude of the corresponding composite muscular action potentials (PACM) in the tenar eminence; When the PACMs were ≤2 mV (equivalent to half the lower limit of normal), proximal segments of the median nerve (axilla-elbow) were examined with registration in the muscles of the forearm.

This study demonstrates that I-CMT comprises 17 loci with 15 cloned genes, which according to their inheritance patterns are distributed as follows: two with X-linked inheritance; 11 with autosomal dominant inheritance (DI-CMT); And the remaining four with autosomal recessive inheritance (RI-CMT). The results of this work indicate that the following changes should be introduced in the OMIM (Online Mendelian Inheritance in Man) catalog: i / leave vacancies items DI-CMTA (MIM # 606483), RI-CMTB (MIM # 3613641) and RI-CMTD (MIM # 616039), since they probably represent examples of axonal forms of CMT with heavy loss of coarse fibers, which leads to false intermediate range conduction; And ii / assign numbering for the CMT associated with mutations of the DRP2, NEFL, MNF2, AARS, MD1 and DCTN2 genes.

In conclusion, I-CMT is a complex syndrome whose characterization requires a specific neurophysiological protocol that includes an evaluation of the proximal nerve trunks of the upper limbs when the distal PACMs are reduced and a revision of the phenotypes collected in OMIM .