The various Charcot–Marie–Tooth diseases

Abstract

CMT disease is the most common inherited neuromuscular disorder, with a fairly homogeneous clinical phenotype (progressive distal muscle weakness and atrophy, foot deformities, distal sensory loss, and depressed tendon reflexes). With more than 40 genes implicated, an update of the present and rather confusing classification of CMT is needed. Over the last few years, new mutated genes have been discovered. Although nerve biopsy is not routinely carried out in CMT neuropathies, it may show characteristic features, which can orientate the search for the mutated gene. There are currently no effective medications for CMT, but clinical trials are ongoing or planned.

Large Conformational Changes of Insertion 3 in Human Glycyl-tRNA Synthetase (hGlyRS) during Catalysis

“…Based on the nerve conduction velocity, CMT can be roughly divided into the CMT1 subtype with demyelinating and reduced nerve conduction velocities, the CMT2 subtype with axonal and moderately reduced or normal nerve conduction velocities, and the intermediate subtypes, respectively (25,26). Subtypes are further classified according to the inheritance patterns and gene mutations, and more than 50 genes are implicated in various subtypes (24,27). CMT subtype 2D begins after young adulthood and causes more severe symptoms in hand than foot (28).…”

“…CMT is one of the most commonly inherited neurological disorders of the peripheral nervous system (22,23), manifested by progressive distal muscle weakness and atrophy or hand and foot deformities. CMT is usually caused by inherited or de novo mutations in genes related to the structures and functions of myelin sheath or axon (24). Based on the nerve conduction velocity, CMT can be roughly divided into the CMT1 subtype with demyelinating and reduced nerve conduction velocities, the CMT2 subtype with axonal and moderately reduced or normal nerve conduction velocities, and the intermediate subtypes, respectively (25,26).…”

Charcot–Marie–Tooth diseases: an update and some new proposals for the classification

“…In spite of this genetic heterogeneity, all forms of CMT have quite a homogeneous clinical phenotype: PMA, skeletal deformities (including pes cavus ), and usually decrease or absence of tendon reflexes 17 27. Other signs, such as pyramidal tract involvement (CMT5) or optic neuropathy (CMT6), may also be observed.…”

“…Most of the CMT diseases are demyelinating (CMT1 for the AD forms and CMT4 for the AR ones), and up to one-third are primarily axonal (type 2: AD-CMT2 and AR-CMT2). In CMT, information of families in term of diagnostic certainty, mode of inheritance, prognosis and sometimes therapeutic trials (see further) requires an accurate genetic diagnosis 27 29. Recently, Saporta et al ,30 in a personal series of >500 patients with CMT, reported that the most prominent CMT subtypes identified were CMT1A (duplication of PMP22 ), CMTX1 (mutations of GJB1 ) , hereditary neuropathy with liability to pressure palsies (deletion of PMP22 ), CMT1B (mutations of MPZ ) and CMT2A (mutations of MFN2 ); other CMT subtypes accounted for <1% of all patients with genetically defined CMT; only 1.8% of patients with CMT1 were without a genetic diagnosis, although 65.6% of patients with CMT2 were in the same situation 30.…”

Dysfunction in the hip joints in children with Charcot-Marie-Tooth syndrome (literature review)

“…Болезнь может наследоваться тремя разными путями -х-сцепленному, аутосомно-до-минантному, аутосомно-рецессивному. В настоя-щее время известно уже более 60 генов, мутации в которых вызывают это заболевание [12][13][14]. Наиболее часто встречается форма 1А заболева-ния (до 80 % случаев) с аутосомно-доминантным типом наследования, в основе которой лежит ду-пликация в локусе 17р11.2, в то время как точеч-ные мутации при заболевании регистрируются во многих генах, но, как правило, их частота невысо-ка и нередко они уникальны [15,16].…”