Review
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World J Neurol. Sep 28, 2013; 3(3): 42-55
Published online Sep 28, 2013. doi: 10.5316/wjn.v3.i3.42
Advances in the molecular diagnosis of Charcot-Marie-Tooth disease
Paschalis Nicolaou, Kyproula Christodoulou
Paschalis Nicolaou, Kyproula Christodoulou, Neurogenetics Department, Cyprus Institute of Neurology and Genetics, 1683 Nicosia, Cyprus
Author contributions: Nicolaou P and Christodoulou K contributed equally to the design, drafting and revision of the manuscript and both approved the final version.
Correspondence to: Kyproula Christodoulou, PhD, Professor of the Cyprus School of Molecular Medicine, Head of the Neurogenetics Department, Cyprus Institute of Neurology and Genetics, 6 International Airport Av., P.O. Box 23462, 1683 Nicosia, Cyprus. roula@cing.ac.cy
Telephone: +357-22-392649 Fax: +357-22-392615
Received: June 28, 2013
Revised: August 1, 2013
Accepted: August 16, 2013
Published online: September 28, 2013
Abstract

Charcot-Marie-Tooth (CMT) disease or hereditary motor and sensory neuropathy is the most common inherited neuromuscular disorder affecting at least 1 in 2500. CMT disease is pathologically and genetically heterogeneous and is characterized by a variable age of onset, slowly progressive weakness and muscle atrophy, starting in the lower limbs and subsequently affecting the upper extremities. Symptoms are usually slowly progressive, especially for the classic and late-onset phenotypes, but can be rather severe in early-onset forms. CMT is grouped into demyelinating, axonal and intermediate forms, based on electrophysiological and pathological findings. The demyelinating types are characterized by severely reduced motor nerve conduction velocities (MNCVs) and mainly by myelin abnormalities. The axonal types are characterized by normal or slightly reduced MNCVs and mainly axonal abnormalities. The intermediate types are characterized by MNCVs between 25 m/s and 45 m/s and they have features of both demyelination and axonopathy. Inheritance can be autosomal dominant, X-linked, or autosomal recessive. Mutations in more than 30 genes have been associated with the different forms of CMT, leading to major advancements in molecular diagnostics of the disease, as well as in the understanding of pathogenetic mechanisms. This editorial aims to provide an account that is practicable and efficient on the current molecular diagnostic procedures for CMT, in correlation with the clinical, pathological and electrophysiological findings. The most frequent causative mutations of CMT will also be outlined.

Keywords: Charcot-Marie-Tooth disease, Charcot-Marie-Tooth, Neuropathy, Genetics, Molecular diagnosis

Core tip: Charcot-Marie-Tooth (CMT) disease is the most common neuromuscular disorder affecting at least 1 in 2500. CMT according to electrophysiological and pathological findings is categorised into demyelinating, axonal and intermediate forms and inheritance can be autosomal dominant, X-linked, or autosomal recessive. More than 30 causative genes have been identified. This editorial aims to present an efficient account of molecular diagnostic procedures for CMT, based on clinical, pathological and electrophysiological findings as well as summarize the most frequent causative mutations.