Denaturing high-performance liquid chromatography of the myotubularin-related 2 gene (MTMR2) in unrelated patients with Charcot-Marie-Tooth disease suggests a low frequency of mutation in inherited neuropathy

Neurogenetics ◽  
2001 ◽  
Vol 3 (2) ◽  
pp. 107-109 ◽  
Author(s):  
Alessandra Bolino ◽  
Lorne J. Lonie ◽  
Michael Zimmer ◽  
Cornelius F. Boerkoel ◽  
Hiroshi Takashima ◽  
...  
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
High Performance ◽  
Low Frequency ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Inherited Neuropathy ◽  
Tooth Disease

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.

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.

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.

Association Between Body Mass Index and Disability in Children With Charcot-Marie-Tooth Disease

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012725
Author(s):  
Gabrielle A. Donlevy ◽  
Sarah P. Garnett ◽  
Kayla M.D. Cornett ◽  
Marnee J. McKay ◽  
Jennifer N. Baldwin ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Task Force ◽  
Healthy Children ◽  
Healthy Weight ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Inherited Neuropathy ◽  
Age And Sex ◽  
Tooth Disease

Objective:This study examined the association between body mass index (BMI) and disability in children with Charcot-Marie-Tooth disease (CMT).Methods:We conducted a cross-sectional analysis of 477 patients with CMT aged 3-20 years from the Inherited Neuropathy Consortium, and 316 age-and-sex matched healthy children from the 1000 Norms Project. BMI was categorised according to the International Obesity Task Force (IOTF) criteria, and BMI categorisation was compared with healthy children. IOTF categories (adult equivalent BMI cut points) were: severely underweight (BMI<17kg/m2); underweight (BMI≥17 to <18.5kg/m2); healthy weight (BMI≥18.5 to <25kg/m2); overweight (BMI ≥25 to <30kg/m2); obese (BMI ≥30kg/m2). Scores on the 0-44 point CMT Pediatric Scale (CMTPedS), a well-validated measure of disability, were examined in relation to BMI.Results:There was a higher proportion of children with CMT categorised as severely underweight (5.7%vs0.3%), underweight (10.3%vs5.1%), and obese (7.3%vs3.8%) (p<0.05). Fewer children with CMT were categorised as healthy weight (61.8%vs74.4%) (p<0.05), and the proportion of overweight (14.9%vs16.5%) between groups was similar. CMTPedS scores (mean ± SD) for weight categories were: severely underweight (27±9), underweight (20±8), healthy weight (17±9), overweight (17±9) obese (22 ±10). Compared to healthy weight children with CMT, being severely underweight was associated with being more disabled (p<0.001), as was being obese (p=0.015).Conclusion:The proportion of underweight and obese children with CMT is higher compared to age-and sex-matched healthy children. Children with CMT who are underweight or obese are associated with greater disability than compared children with CMT of healthy weight.

scholarly journals Targeted PMP22 TATA-box editing by CRISPR/Cas9 reduces demyelinating neuropathy of Charcot-Marie-Tooth disease type 1A in mice

2019 ◽  
Author(s):  
Ji-Su Lee ◽  
Jae Y Lee ◽  
Dong W Song ◽  
Hee S Bae ◽  
Hyun M Doo ◽  
...  
Keyword(s):  
Tata Box ◽  
Chromosome 17 ◽  
Gene Encoding ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Inherited Neuropathy ◽  
Its Gene ◽  
Multiple Copies ◽  
Human Chromosome 17 ◽  
Tooth Disease

Abstract Charcot-Marie-Tooth 1A (CMT1A) is the most common inherited neuropathy without a known therapy, which is caused by a 1.4 Mb duplication on human chromosome 17, which includes the gene encoding the peripheral myelin protein of 22 kDa (PMP22). Overexpressed PMP22 protein from its gene duplication is thought to cause demyelination and subsequently axonal degeneration in the peripheral nervous system (PNS). Here, we targeted TATA-box of human PMP22 promoter to normalize overexpressed PMP22 level in C22 mice, a mouse model of CMT1A harboring multiple copies of human PMP22. Direct local intraneural delivery of CRISPR/Cas9 designed to target TATA-box of PMP22 before the onset of disease, downregulates gene expression of PMP22 and preserves both myelin and axons. Notably, the same approach was effective in partial rescue of demyelination even after the onset of disease. Collectively, our data present a proof-of-concept that CRISPR/Cas9-mediated targeting of TATA-box can be utilized to treat CMT1A.

scholarly journals Effects of Self-Selected Exercise on Strength in Charcot–Marie–Tooth Disease Subtypes

2017 ◽  
Vol 44 (5) ◽  
pp. 572-576
Author(s):  
Djurdja Djordjevic ◽  
Sabrina Fell ◽  
Steven Baker
Keyword(s):  
Retrospective Chart Review ◽  
Elbow Flexion ◽  
Normative Values ◽  
Future Research ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Hand Grip ◽  
Inherited Neuropathy ◽  
Type Of Exercise ◽  
Tooth Disease

AbstractBackground: Preliminary studies have supported the utility of exercise as a treatment for Charcot–Marie–Tooth disease (CMT) patients. Despite being the most common inherited neuropathy, there remains a paucity of guidelines for CMT management. Methods: A retrospective chart review was performed on 297 CMT patients. Self-reported exercise and strength results from standardized dynamometer testing were obtained from adult patients’ first visits. Values were converted and analyzed based on previously reported age- and sex-matched normative values. Results: Participants with CMT2 had greater strength values than those with CMT1 in hand grip, elbow flexion, and dorsiflexion (p<0.05). Participants with CMT1 and CMT2 who exercised were statistically significantly stronger in elbow flexion and dorsiflexion than those who did not exercise. Conclusions: These preliminary results suggest that self-directed exercise is associated with greater strength in CMT patients of both CMT1 and CMT2 subtypes. Self-directed exercise may be a convenient, sustainable, and effective method of improving strength and decreasing disability in this population. Future research should explore the type of exercise prescription that best addresses the needs of the CMT population.

scholarly journals Treatment-induced remission of medulloblastoma using a chemotherapeutic regimen devoid of vincristine in a child with Charcot–Marie–Tooth disease

2019 ◽  
Vol 26 (2) ◽  
Author(s):  
J. D. Bernstock ◽  
J. L. Cohen ◽  
S. Singh ◽  
C. W. Schlappi ◽  
J. B. Fiveash ◽  
...  
Keyword(s):  
Standard Treatment ◽  
Sensory Loss ◽  
Neoplastic Disease ◽  
Standard Drug ◽  
Chemotherapeutic Regimen ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Inherited Neuropathy ◽  
Tooth Disease ◽  
Core Features

Charcot–Marie–Tooth (cmt) disease is the most common form of inherited neuropathy. Core features include peripheral neuropathy and secondary axonal degeneration, with a noted distal predominance of limb-muscle wasting, weakness, and sensory loss. Given the significant prevalence of cmt, superimposed neoplastic disease can be encountered within this patient population. Malignancies that are treated with vincristine (a microtubule-targeting agent), even at low doses as part of standard treatment, pose a significant challenge for patients with cmt. Here, we present the case of a child with cmt who was successfully treated for medulloblastoma without vincristine, a standard drug used for treatment of that disease, to avoid the risk of severe debilitating neuropathy. This report is the first of a patient successfully treated for medulloblastoma without vincristine.

scholarly journals P.072 Effects of self-directed exercise on strength in Charcot-Marie-Tooth disease subtypes

2017 ◽  
Vol 44 (S2) ◽  
pp. S31-S31
Author(s):  
D Djordjevic ◽  
S Baker ◽  
S Fell
Keyword(s):  
Retrospective Chart Review ◽  
Elbow Flexion ◽  
Normative Values ◽  
Future Research ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Hand Grip ◽  
Inherited Neuropathy ◽  
Type Of Exercise ◽  
Tooth Disease

Background: Preliminary studies have supported the utility of exercise as a treatment for Charcot-Marie-Tooth disease (CMT) patients. Despite being the most common inherited neuropathy, there remains a paucity of guidelines for CMT management. Methods: A retrospective chart review was performed on 297 CMT patients. Self-reported exercise and strength results from standardized dynamometer testing were obtained from adult patients’ first visits. Values were converted and analyzed based on previously reported age and sex matched normative values. Results: Participants with CMT2 were stronger than CMT1 in hand grip, elbow flexion, and dorsiflexion (p<0.05). CMT1A participants were weaker than those with CMT1B/D. Participants with CMT1 and CMT2 who exercised were statistically significantly stronger in elbow flexion and dorsiflexion than those who did not exercise. Conclusions: These preliminary results suggest that self-directed exercise is associated with greater strength in patients with CMT. Furthermore, they support the evidence that the dysmyelinating process in CMT1 may lead to greater loss of strength compared to the axonal degeneration in CMT2, and that exercise may benefit both subtypes. Self-directed exercise may be a convenient, sustainable, and effective method of improving strength and decreasing disability in these individuals. Future research should explore the type of exercise prescription that best addresses the needs of the CMT population.

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