scholarly journals PROGRESS IN CLINICAL NEUROSCIENCES: Charcot-Marie-Tooth Disease and Related Inherited Peripheral Neuropathies

2001 ◽  
Vol 28 (3) ◽  
pp. 199-214 ◽  
Author(s):  
Timothy J. Benstead ◽  
Ian A. Grant
Keyword(s):  
Molecular Genetic ◽  
Charcot Marie Tooth ◽  
Hereditary Motor ◽  
Charcot Marie Tooth Disease ◽  
Inherited Neuropathy ◽  
Molecular Aspects ◽  
The Many ◽  
Inherited Neuropathies ◽  
Tooth Disease

The classification of Charcot-Marie-Tooth disease and related hereditary motor and sensory neuropathies has evolved to incorporate clinical, electrophysiological and burgeoning molecular genetic information that characterize the many disorders. For several inherited neuropathies, the gene product abnormality is known and for others, candidate genes have been identified. Genetic testing can pinpoint a specific inherited neuropathy for many patients. However, clinical and electrophysiological assessments continue to be essential tools for diagnosis and management of this disease group. This article reviews clinical, electrophysiological, pathological and molecular aspects of hereditary motor and sensory neuropathies.

scholarly journals A murine model of Charcot-Marie-Tooth disease 4F reveals a role for the C-terminus of periaxin in the formation and stabilization of Cajal bands

2018 ◽  
Vol 3 ◽  
pp. 20 ◽  
Author(s):  
Diane L. Sherman ◽  
Peter J. Brophy
Keyword(s):  
Plasma Membrane ◽  
Schwann Cell ◽  
Laminin Receptor ◽  
Cell Plasma Membrane ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
C Terminus ◽  
Cell Plasma ◽  
Inherited Neuropathies ◽  
Tooth Disease

Charcot-Marie-Tooth (CMT) disease comprises up to 80 monogenic inherited neuropathies of the peripheral nervous system (PNS) that collectively result in demyelination and axon degeneration. The majority of CMT disease is primarily either dysmyelinating or demyelinating in which mutations affect the ability of Schwann cells to either assemble or stabilize peripheral nerve myelin. CMT4F is a recessive demyelinating form of the disease caused by mutations in the Periaxin (PRX) gene. Periaxin (Prx) interacts with Dystrophin Related Protein 2 (Drp2) in an adhesion complex with the laminin receptor Dystroglycan (Dag). In mice the Prx/Drp2/Dag complex assembles adhesive domains at the interface between the abaxonal surface of the myelin sheath and the cytoplasmic surface of the Schwann cell plasma membrane. Assembly of these appositions causes the formation of cytoplasmic channels called Cajal bands beneath the surface of the Schwann cell plasma membrane. Loss of either Periaxin or Drp2 disrupts the appositions and causes CMT in both mouse and man. In a mouse model of CMT4F, complete loss of Periaxin first prevents normal Schwann cell elongation resulting in abnormally short internodal distances which can reduce nerve conduction velocity, and subsequently precipitates demyelination. Distinct functional domains responsible for Periaxin homodimerization and interaction with Drp2 to form the Prx/Drp2/Dag complex have been identified at the N-terminus of Periaxin. However, CMT4F can also be caused by a mutation that results in the truncation of Periaxin at the extreme C-terminus with the loss of 391 amino acids. By modelling this in mice, we show that loss of the C-terminus of Periaxin results in a surprising reduction in Drp2. This would be predicted to cause the observed instability of both appositions and myelin, and contribute significantly to the clinical phenotype in CMT4F.

Biomechanical effects of sensorimotor orthoses in adults with Charcot–Marie–Tooth disease

2015 ◽  
Vol 40 (4) ◽  
pp. 436-446 ◽  
Author(s):  
Caleb Wegener ◽  
Katrin Wegener ◽  
Richard Smith ◽  
Karl-Heinz Schott ◽  
Joshua Burns
Keyword(s):  
Lower Limb ◽  
Repeated Measures ◽  
Three Dimensional ◽  
Walking Ability ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Inherited Neuropathy ◽  
Custom Made ◽  
Patient Reported ◽  
Tooth Disease

Background: Charcot–Marie–Tooth disease is an inherited neuropathy causing progressive weakness, foot deformity and difficulty walking. Clinical anecdotes suggest orthoses designed on the ‘sensorimotor’ paradigm are beneficial for improving gait in Charcot–Marie–Tooth disease. Objectives: Investigate the effect of sensorimotor orthoses on in-shoe and lower limb biomechanics in adults with Charcot–Marie–Tooth disease. Study design: Randomised, repeated-measures, exploratory study. Methods: Eight males and two females with Charcot–Marie–Tooth disease aged 31–68 years fitted with pedorthic shoes and custom-made sensorimotor orthoses were randomly tested at baseline and after 4 weeks of adaptation. In-shoe three-dimensional multi-segment foot and lower limb kinematics and kinetics were collected as were plantar pressures, electromyography and self-reported comfort, stability, cushioning and preference. Results: Compared to the shoe only condition, sensorimotor orthoses increased midfoot eversion and plantarflexion, increased ankle eversion and produced small but significant changes at the knee and hip indicating increased internal rotation. The orthoses increased medial ground reaction forces and increased pressure at the heel, midfoot and toes. There were minimal effects on electromyography. The sensorimotor orthoses were rated higher for comfort, cushioning, stability and preference. Conclusion: Sensorimotor orthoses produced changes in kinematic, kinetic and pressure variables in adults with Charcot–Marie–Tooth disease and were regarded as more comfortable, cushioned and stable during walking. Clinical relevance In this study, the walking ability of patients with Charcot–Marie–Tooth disease improved with the use of foot orthoses designed according to the sensorimotor paradigm. However, the mechanism of action appears to be primarily mechanical in origin. Randomised controlled trials are necessary to evaluate the long-term patient-reported outcomes of sensorimotor orthoses.

Case 22

2018 ◽  
Author(s):  
Bashar Katirji
Keyword(s):  
Differential Diagnosis ◽  
Clinical Practice ◽  
Nerve Conduction ◽  
Nerve Conduction Studies ◽  
Genetic Defects ◽  
Neurological Manifestations ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Inherited Neuropathy ◽  
Tooth Disease

Charcot-Marie-Tooth disease is the most common inherited neuropathy encountered in clinical practice. The disorder encompasses a large number of subtypes; most share common neurological manifestations. Charcot-Marie-Tooth disease is often subdivided into many subtypes based on pathophysiological or inheritance patterns. There are demyelinating and axonal types, as well as dominant, recessive, or X-linked forms. This case presents a typical patient with Charcot-Marie-Tooth disease and highlights the neurological findings. This is followed by emphasis on the findings seen on nerve conduction studies showing the differences between the demyelinating, axonal, and intermediate types. A list of the known genetic defects described so far is presented. A working and practical differential diagnosis and algorithm is also suggested.

Diaphragmatic Dysfunction in Siblings with Hereditary Motor and Sensory Neuropathy (Charcot-Marie-Tooth Disease)

CHEST Journal ◽  
1987 ◽  
Vol 91 (4) ◽  
pp. 567-570 ◽  
Author(s):  
Charles K. Chan ◽  
Vahid Mohsenin ◽  
Jacob Loke ◽  
Jim Virgulto ◽  
M. Leonide Sipski ◽  
...  
Keyword(s):  
Sensory Neuropathy ◽  
Diaphragmatic Dysfunction ◽  
Charcot Marie Tooth ◽  
Hereditary Motor ◽  
Charcot Marie Tooth Disease ◽  
Tooth Disease ◽  
Motor And Sensory Neuropathy

Allelic heterogeneity in hereditary motor and sensory neuropathy type la (Charcot-Marie-Tooth disease type 1a)

Neurology ◽  
1993 ◽  
Vol 43 (5) ◽  
pp. 1010-1010 ◽  
Author(s):  
J. E. Hoogendijk ◽  
E.A.M. Janssen ◽  
A. A.W.M. Gabreels-Festen ◽  
G. W. Hensels ◽  
E. M.G. Joosten ◽  
...  
Keyword(s):  
Sensory Neuropathy ◽  
Disease Type ◽  
Allelic Heterogeneity ◽  
Charcot Marie Tooth ◽  
Hereditary Motor ◽  
Charcot Marie Tooth Disease ◽  
Tooth Disease ◽  
Motor And Sensory Neuropathy

scholarly journals Epidemiologic Study of Charcot-Marie-Tooth Disease: A Systematic Review

2016 ◽  
Vol 46 (3) ◽  
pp. 157-165 ◽  
Author(s):  
Lidiane Carine Lima Santos Barreto ◽  
Fernanda Santos Oliveira ◽  
Paula Santos Nunes ◽  
Iandra Maria Pinheiro de França Costa ◽  
Catarina Andrade Garcez ◽  
...  
Keyword(s):  
Epidemiologic Study ◽  
Inclusion Criteria ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
The United Kingdom ◽  
Inherited Neuropathy ◽  
Tooth Disease

Background: Charcot-Marie-Tooth disease (CMT) is the most common inherited neuropathy. CMT is classified into 2 main subgroups: CMT type 1 (CMT1; demyelinating form) and CMT type 2 (CMT2; axonal form). The objectives of this study were to systematically review and assess the quality of studies reporting the incidence and/or prevalence of CMT worldwide. Summary: A total of 802 studies were initially identified, with only 12 meeting the inclusion criteria. CMT prevalence was reported in 10 studies and ranged from 9.7/100,000 in Serbia to 82.3/100,000 in Norway. The frequency of the main subtypes varied from 37.6 to 84% for CMT1 and from 12 to 35.9% for CMT2; the country with the lowest prevalence of CMT1 was Norway, and the country with the highest prevalence of CMT1 was Iceland; on the other hand, CMT2 was least prevalent in the United Kingdom and most prevalent in Norway. Key Messages: This review reveals the gaps that still exist in the epidemiological knowledge of CMT around the world. Published studies are of varying quality and utilise different methodologies, thus precluding a robust conclusion. Additional research focusing on epidemiological features of CMT in different nations and different ethnic groups is needed.

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