Autosomal recessive Charcot-Marie-Tooth disease: from genes to phenotypes

Authors

  • Meriem Tazir,

    Corresponding author
    1. Laboratoire de NeuroSciences, Université d'Alger 1, Alger, Algeria
    • Service de Neurologie, University Hospital Mustapha Bacha, Alger, Algeria
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  • Mounia Bellatache,

    1. Service de Neurologie, University Hospital Mustapha Bacha, Alger, Algeria
    2. Laboratoire de NeuroSciences, Université d'Alger 1, Alger, Algeria
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  • Sonia Nouioua,

    1. Service de Neurologie, University Hospital Mustapha Bacha, Alger, Algeria
    2. Laboratoire de NeuroSciences, Université d'Alger 1, Alger, Algeria
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  • Jean-Michel Vallat

    1. Centre de Référence ⟨Neuropathies Périphériques Rares⟩, Service et Laboratoire de Neurologie, University Hospital, Limoges, France
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Address correspondence to: Meriem Tazir, Service de Neurologie, Centre Hospital-Universitaire Mustapha Bacha, 1 place de la Concorde, Alger 16000, Algeria. Tel: +(213)21-2-35640; Fax: +(213)21-2-35640; E-mail: meriem.tazir@sante.dz

Abstract

The prevalence of Charcot-Marie-Tooth (CMT) disease or hereditary motor and sensory neuropathy (HMSN) varies in different populations. While in some countries of Western Europe, the United States and Japan the dominant form of HMSN is the most frequent, in other countries such as those of the Mediterranean Basin, the autosomal recessive form (AR-CMT) is more common. Autosomal recessive CMT cases are generally characterized by earlier onset, usually before the age of 2 or 3  years, and rapid clinical progression that results in severe polyneuropathy and more marked distal limb deformities such as pes equino-varus, claw-like hands, and often major spinal deformities. Recent clinical, morphological and molecular investigations of CMT families with autosomal recessive inheritance allowed the identification of many genes such as GDAP1, MTMR2, SBF2, NDRG1, EGR2, SH3TC2, PRX, FGD4, and FIG4, implicated in demyelinating forms (ARCMT1 or CMT4), and LMNA, MED25, HINT1, GDAP1, LRSAM1, NEFL, HSPB1 and MFN2 in axonal forms (ARCMT2). However, many patients remain without genetic diagnosis to date, prompting investigations into ARCMT families in order to help discover new genes and common pathways. This review summarizes recent advances regarding the genotypes and corresponding phenotypes of AR-CMT.

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