Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (657 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
A hereditary motor and sensory neuropathy transmitted most often as an autosomal dominant trait and characterized by progressive distal wasting and loss of reflexes in the muscles of the legs (and occasionally involving the arms). Onset is usually in the second to fourth decade of life. This condition has been divided into two subtypes, hereditary motor and sensory neuropathy (HMSN) types I and II. HMSN I is associated with abnormal nerve conduction velocities and nerve hypertrophy, features not seen in HMSN II. (Adams et al., Principles of Neurology, 6th ed, p1343)
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Charcot Marie Tooth Disease; Muscular Atrophy, Peroneal; Atrophies, Peroneal Muscular; Atrophy, Peroneal Muscular; Muscular Atrophies, Peroneal; Peroneal Muscular Atrophies; Peroneal Muscular Atrophy; Charcot-Marie-Tooth Syndrome.
Where it fits in the MeSH classification
- Broader topics
- Hereditary Sensory and Motor Neuropathy
- See also
- Myelin P0 Protein
Research landscape
PubMed indexes 4,945 records tagged with the MeSH heading “Charcot-Marie-Tooth Disease” (counts retrieved 2026-10-29). 1,076 of them (21.8%) were published from 2020 onward, and the busiest period so far is 2010-2019 with 1,583 records.
Reviews account for 662 records (13.4%) and meta-analyses for 12. Randomized controlled trials number 34 (0.7%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 1,146 |
| 2000-2009 | 1,140 |
| 2010-2019 | 1,583 |
| 2020 onward | 1,076 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 662 | 13.4% |
| Meta-analyses | 12 | 0.2% |
| Randomized controlled trials | 34 | 0.7% |
Method: PubMed query "Charcot-Marie-Tooth Disease"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.
Reading the evidence in rare and inherited diseases
Rare conditions are difficult to study: few patients means small studies, case reports and registries are common, and randomized trials are the exception. Small samples limit precision and can exaggerate effects, and cases reported in the literature may be the most severe or unusual. Evidence from many small studies is best read together. Check how patients were identified, how many were included and how long they were followed.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| The Balance of MFN2 and OPA1 in Mitochondrial Dynamics, Cellular Homeostasis, and Disease | 2025 | Review article Design not recorded in structured metadata | 86 | cc by PMID 40149969 · DOI · PMC11940761 |
| Small heat shock proteins in neurodegenerative diseases | 2020 | Review article Design not recorded in structured metadata | 86 | cc by PMID 32323160 · DOI · PMC7332613 |
| Emerging Therapies for Charcot-Marie-Tooth Inherited Neuropathies | 2021 | Review article Design not recorded in structured metadata | 56 | cc by PMID 34205075 · DOI · PMC8199910 |
| Aberrant Molecular Myelin Architecture in Charcot-Marie-Tooth Disease Type 1A and Hereditary Neuropathy With Liability to Pressure Palsies | 2026 | Research article Design not recorded in structured metadata | 1 | cc by PMID 41400104 · DOI · PMC12706824 |
The Balance of MFN2 and OPA1 in Mitochondrial Dynamics, Cellular Homeostasis, and Disease [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Mitochondrial dynamics, governed by fusion and fission, are crucial for maintaining cellular homeostasis, energy production, and stress adaptation.
- Closing excerpt
- Finally, we highlight emerging therapeutic strategies to restore mitochondrial integrity, including mTOR modulation and autophagy-targeted approaches, with potential implications for neurodegenerative disorders.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (142 words)
Mitochondrial dynamics, governed by fusion and fission, are crucial for maintaining cellular homeostasis, energy production, and stress adaptation. MFN2 and OPA1, key regulators of mitochondrial fusion, play essential roles beyond their structural functions, influencing bioenergetics, intracellular signaling, and quality control mechanisms such as mitophagy. Disruptions in these processes, often caused by MFN2 or OPA1 mutations, are linked to neurodegenerative diseases like Charcot-Marie-Tooth disease type 2A (CMT2A) and autosomal dominant optic atrophy (ADOA). This review explores the molecular mechanisms underlying mitochondrial fusion, the impact of MFN2 and OPA1 dysfunction on oxidative phosphorylation and autophagy, and their role in disease progression. Additionally, we discuss the divergent cellular responses to MFN2 and OPA1 mutations, particularly in terms of proliferation, senescence, and metabolic signaling. Finally, we highlight emerging therapeutic strategies to restore mitochondrial integrity, including mTOR modulation and autophagy-targeted approaches, with potential implications for neurodegenerative disorders.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 40149969 · DOI · PMC11940761
Small heat shock proteins in neurodegenerative diseases [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Small heat shock proteins are ubiquitously expressed chaperones, yet mutations in some of them cause tissue-specific diseases.
- Closing excerpt
- The second part of the paper will discuss how small heat shock proteins are linked to neurodegenerative disorders like Alzheimer's, Parkinson's, and Huntington's disease.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (108 words)
Small heat shock proteins are ubiquitously expressed chaperones, yet mutations in some of them cause tissue-specific diseases. Here, we will discuss how small heat shock proteins give rise to neurodegenerative disorders themselves while we will also highlight how these proteins can fulfil protective functions in neurodegenerative disorders caused by protein aggregation. The first half of this paper will be focused on how mutations in HSPB1, HSPB3, and HSPB8 are linked to inherited peripheral neuropathies like Charcot-Marie-Tooth (CMT) disease and distal hereditary motor neuropathy (dHMN). The second part of the paper will discuss how small heat shock proteins are linked to neurodegenerative disorders like Alzheimer's, Parkinson's, and Huntington's disease.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 32323160 · DOI · PMC7332613
Emerging Therapies for Charcot-Marie-Tooth Inherited Neuropathies [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Inherited neuropathies known as Charcot-Marie-Tooth (CMT) disease are genetically heterogeneous disorders affecting the peripheral nerves, causing significant and slowly progressive disability over the lifespan.
- Closing excerpt
- As promising treatments reach the stage of clinical translation, optimal outcome measures, novel biomarkers and appropriate trial designs are crucial in order to facilitate successful testing and validation of novel treatments for CMT patients.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (157 words)
Inherited neuropathies known as Charcot-Marie-Tooth (CMT) disease are genetically heterogeneous disorders affecting the peripheral nerves, causing significant and slowly progressive disability over the lifespan. The discovery of their diverse molecular genetic mechanisms over the past three decades has provided the basis for developing a wide range of therapeutics, leading to an exciting era of finding treatments for this, until now, incurable group of diseases. Many treatment approaches, including gene silencing and gene replacement therapies, as well as small molecule treatments are currently in preclinical testing while several have also reached clinical trial stage. Some of the treatment approaches are disease-specific targeted to the unique disease mechanism of each CMT form, while other therapeutics target common pathways shared by several or all CMT types. As promising treatments reach the stage of clinical translation, optimal outcome measures, novel biomarkers and appropriate trial designs are crucial in order to facilitate successful testing and validation of novel treatments for CMT patients.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 34205075 · DOI · PMC8199910
Aberrant Molecular Myelin Architecture in Charcot-Marie-Tooth Disease Type 1A and Hereditary Neuropathy With Liability to Pressure Palsies [4]
Abstract reading summary — source excerpts
- Opening excerpt
- Charcot-Marie-Tooth Disease Type 1A (CMT1A) and Hereditary Neuropathy with Liability to Pressure Palsies (HNPP) are the most common inherited peripheral neuropathies and arise from copy number variation of the Peripheral Myelin Protein 22 (PMP22) gene.
- Closing excerpt
- This work also identifies junctional complexes as potential actionable molecular targets and establishes a mechanistic framework applicable to a broad spectrum of inherited dysmyelinating and acquired demyelinating neuropathies.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (250 words)
Charcot-Marie-Tooth Disease Type 1A (CMT1A) and Hereditary Neuropathy with Liability to Pressure Palsies (HNPP) are the most common inherited peripheral neuropathies and arise from copy number variation of the Peripheral Myelin Protein 22 (PMP22) gene. While secondary axon degeneration has been proposed as the primary driver of disability, our prior work demonstrated pronounced neuromuscular impairment in CMT1A model mice in the absence of overt axonal loss, prompting investigation into primary myelin dysfunction. Here, we reveal that altered PMP22 dosage profoundly disrupts molecular architecture at critical myelin domains, Schmidt-Lanterman incisures (SLIs) and Nodes of Ranvier. Using high-resolution confocal imaging of teased peripheral nerve fibers from CMT1A and HNPP model mice, we identified widespread disorganization of adherens junctions, mislocalization of Connexin29 and aberrant distribution of nodal ion channels, with several defects more severe in CMT1A, consistent with disease burden. Notably, nodal widening and abnormal spreading of Kv1.2 and Caspr along internodes indicate compromised axo-glial compartmentalization essential for saltatory conduction. Together, these findings support a model in which PMP22 functions as a structural organizer of myelin, coordinating adherens junction patterning and nodal subdomain integrity. Dysregulation of this function is predicted to compromise Schwann-cell architecture, metabolic support and axonal excitability. Our findings support a paradigm shift in which molecular destabilization of myelin, rather than secondary axonal degeneration alone, contributes to disease progression in CMT1A and HNPP. This work also identifies junctional complexes as potential actionable molecular targets and establishes a mechanistic framework applicable to a broad spectrum of inherited dysmyelinating and acquired demyelinating neuropathies.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41400104 · DOI · PMC12706824
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Diagnosis, natural history, and management of Charcot-Marie-Tooth disease [5]
- Research article Human laminopathies: nuclei gone genetically awry [6]
- Research article Epidemiologic Study of Charcot-Marie-Tooth Disease: A Systematic Review [7]
- Research article Charcot-Marie-Tooth disease [8]
- Research article Next-generation sequencing in Charcot-Marie-Tooth disease: opportunities and challenges [9]
- Research article Charcot-Marie-Tooth: From Molecules to Therapy [10]
References
- Zanfardino P, Amati A, Perrone M, Petruzzella V. The Balance of MFN2 and OPA1 in Mitochondrial Dynamics, Cellular Homeostasis, and Disease. . 2025. PMID 40149969 · DOI · PMC11940761
- Vendredy L, Adriaenssens E, Timmerman V. Small heat shock proteins in neurodegenerative diseases. . 2020. PMID 32323160 · DOI · PMC7332613
- Stavrou M, Sargiannidou I, Georgiou E, Kagiava A, Kleopa KA. Emerging Therapies for Charcot-Marie-Tooth Inherited Neuropathies. . 2021. PMID 34205075 · DOI · PMC8199910
- Moss KR, Arowolo MA, Gutierrez DR, Höke A. Aberrant Molecular Myelin Architecture in Charcot-Marie-Tooth Disease Type 1A and Hereditary Neuropathy With Liability to Pressure Palsies. . 2026. PMID 41400104 · DOI · PMC12706824
- Pareyson D, Marchesi C. Diagnosis, natural history, and management of Charcot-Marie-Tooth disease. Lancet Neurol. 2009. PMID 19539237 · DOI
- Capell BC, Collins FS. Human laminopathies: nuclei gone genetically awry. Nat Rev Genet. 2006. PMID 17139325 · DOI
- Barreto LC, Oliveira FS, Nunes PS, de França Costa IM, Garcez CA, Goes GM, et al.. Epidemiologic Study of Charcot-Marie-Tooth Disease: A Systematic Review. Neuroepidemiology. 2016. PMID 26849231 · DOI
- Reilly MM, Murphy SM, Laurá M. Charcot-Marie-Tooth disease. J Peripher Nerv Syst. 2011. PMID 21504497 · DOI
- Pipis M, Rossor AM, Laura M, Reilly MM. Next-generation sequencing in Charcot-Marie-Tooth disease: opportunities and challenges. Nat Rev Neurol. 2019. PMID 31582811 · DOI
- Morena J, Gupta A, Hoyle JC. Charcot-Marie-Tooth: From Molecules to Therapy. Int J Mol Sci. 2019. PMID 31336816 · DOI · PMC6679156
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-29.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.