Materiały źródłowe

• #1 Charcot-Marie-Tooth Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562163/

  Charcot-Marie-Tooth (CMT) disease is the most common inherited neuromuscular disorder, characterized by progressive weakness of the extremities due to peripheral nerve damage. […] The diagnosis of CMT, which involves clinical evaluation, electrophysiology, imaging, and genetic testing, is essential for patient education and counseling, initiating a rehabilitation program, and considering therapeutic trials. […] Screen patients with suspected Charcot-Marie-Tooth disease using comprehensive clinical evaluation, electrophysiology, and genetic testing to confirm diagnosis and assess disease severity. […] Genetic testing is the standard for establishing a conclusive diagnosis, providing medical counseling, aiding reproductive planning, and selecting patients for therapeutic trials and research.

• #2 Charcot-Marie-Tooth Disease | National Institute of Neurological Disorders and Stroke

  https://www.ninds.nih.gov/health-information/disorders/charcot-marie-tooth-disease

  To diagnose CMT, doctors start with a detailed medical and family history. It may be necessary to see a specialist like a neurologist to confirm diagnosis. […] The doctor may order diagnostic tests, which can include: nerve conduction studies, electromyography (EMG), genetic testing, nerve biopsy. […] There is no cure for CMT, but treatments can help manage symptoms. It is important to maintain mobility, flexibility, and muscle strength as much as possible. Starting a treatment program soon after symptoms begin can help people maintain quality of life.

• #3 Charcot-Marie-Tooth disease – Diagnosis & treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/charcot-marie-tooth-disease/diagnosis-treatment/drc-20350522

  During the physical exam, your doctor may check for: […] Your doctor may also recommend the following tests, which can help provide information about the extent of your nerve damage and what may be causing it. […] Nerve conduction studies. These tests measure the strength and speed of electrical signals transmitted through your nerves. […] Electromyography (EMG). A thin needle electrode is inserted through your skin into the muscle. […] Nerve biopsy. A small piece of peripheral nerve is taken from your calf through an incision in your skin. […] Genetic testing. These tests, which can detect the most common genetic defects known to cause Charcot-Marie-Tooth disease, are done with a blood sample. […] Have you or others in your family had genetic testing to confirm the diagnosis?

• #4

  https://www.nhs.uk/conditions/charcot-marie-tooth-disease/diagnosis/

  If you have early symptoms of Charcot-Marie-Tooth disease (CMT), your GP will ask about your symptoms and may carry out a physical examination. […] During a physical examination, your GP will look for evidence of the condition, such as muscle weakness, poor or absent reflexes, and foot deformities, such as high arches or flat feet. […] If CMT is suspected, you may be referred to a doctor who specialises in treating conditions of the nervous system (a neurologist) for further testing. […] A nerve conduction test measures the strength and speed of signals transmitted through your peripheral nerves, the network of nerves that run from the brain and spinal cord to and from the rest of the body, such as the limbs and organs. […] Some types of CMT cause a distinctive change in the pattern of electrical activity that can be detected by an EMG.

• #5 Diagnosis – Charcot-Marie-Tooth Disease (CMT) – Diseases | Muscular Dystrophy Association

  https://www.mda.org/disease/charcot-marie-tooth/diagnosis

  A comprehensive history and physical examination remain the core of ascertainment of and evaluation for cases of CMT. […] During this initial evaluation, a neurologist will ask about a patients family history. A family history of CMT-like symptoms, combined with signs of nerve damage from an individuals physical exam, could strongly point to CMT or another hereditary neuropathy. […] To look for sensory loss, a neurologist will usually test a patients deep tendon reflexes (such as the knee-jerk reflex), which are reduced or absent in most people with CMT. […] The neurologist also may perform a nerve conduction velocity (NCV) test, which measures the strength and speed of electrical signals transmitted through nerves. […] Other procedures sometimes used to diagnose CMT include electromyography (EMG), which measures the electrical signals in muscles, and less commonly, nerve biopsy, which involves the removal and examination of a small piece of nerve. […] Next, if the diagnosis is still consistent with CMT, a neurologist may arrange for genetic testing. […] A positive genetic test result can provide a definite diagnosis and useful information for family planning. But once again, a negative genetic test result does not rule out CMT.

• #6 Charcot-Marie-Tooth disease (CMT) | Better Health Channel

  https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/charcot-marie-tooth-disease-cmt

  CMT is diagnosed using a number of tests including: […] physical examination strength testing and assessment of reflexes and sensation. Common findings in CMT are loss of the muscle stretch reflexes (especially the ankle jerk reflex), and weakness with lifting the feet (ankle dorsiflexion) and bringing the thumb upwards (thumb abduction) […] nerve conduction tests used to measure the strength and speed of nerve signals in the peripheral nervous system to determine which form of CMT is present. (Different types of CMT affect different aspects of the nervous system.) For example, nerve responses are much smaller than usual in axonal CMT, and the speed at which nerves are able to send signals is much slower in demyelinating forms of CMT […] genetic tests to identify the altered gene. For example, CMT Type 1A can be diagnosed using a relatively routine test called a chromosome microarray […] biopsy small samples of tissue are removed and examined in a laboratory. Either nerve or muscle tissue (or both) may be examined. This is not commonly done and is usually unnecessary if a genetic alteration is found.

• #7 Diagnosis – Charcot-Marie-Tooth Disease (CMT) – Diseases | Muscular Dystrophy Association

  https://www.mda.org/disease/charcot-marie-tooth/diagnosis

  A comprehensive history and physical examination remain the core of ascertainment of and evaluation for cases of CMT. […] During this initial evaluation, a neurologist will ask about a patients family history. A family history of CMT-like symptoms, combined with signs of nerve damage from an individuals physical exam, could strongly point to CMT or another hereditary neuropathy. […] To look for sensory loss, a neurologist will usually test a patients deep tendon reflexes (such as the knee-jerk reflex), which are reduced or absent in most people with CMT. […] The neurologist also may perform a nerve conduction velocity (NCV) test, which measures the strength and speed of electrical signals transmitted through nerves. […] Other procedures sometimes used to diagnose CMT include electromyography (EMG), which measures the electrical signals in muscles, and less commonly, nerve biopsy, which involves the removal and examination of a small piece of nerve. […] Next, if the diagnosis is still consistent with CMT, a neurologist may arrange for genetic testing. […] A positive genetic test result can provide a definite diagnosis and useful information for family planning. But once again, a negative genetic test result does not rule out CMT.

• #8 Charcot–Marie–Tooth disease – Wikipedia

  https://en.wikipedia.org/wiki/Charcot%E2%80%93Marie%E2%80%93Tooth_disease

  Charcot-Marie-Tooth (CMT) disease can be diagnosed using a combination of three primary methods: nerve conduction studies, nerve biopsy, and genetic testing. Nerve conduction studies assess the velocity of electrical impulses traveling through nerves, whereas nerve biopsy entails the examination of small samples of nerve tissue. Genetic testing can conclusively diagnose CMT by identifying specific mutations linked to the condition. […] Initial signs of CMT often include lower leg weakness, such as foot drop, and foot deformities like high arches or hammertoes. However, these symptoms alone do not provide enough information for a diagnosis. Individuals showing signs of CMT should be referred to a neurologist or rehabilitation medicine specialist for further evaluation and treatment. […] A detailed family history is also important, as CMT is an inherited condition. While the absence of a family history does not rule out CMT, it can help the physician distinguish it from other causes of neuropathy, such as diabetes, toxin exposure, or certain medications.

• #9 Diagnosis | Northwestern Medicine

  https://www.nm.org/conditions-and-care-areas/neurosciences/peripheral-neuropathy-clinic-at-northwestern-memorial-hospital/charcot-marie-tooth-disease/diagnosis

  CMT is a hereditary disorder, almost always caused by a genetic mutation that you inherited from one or both of your parents. There are more than 80 known genetic mutations that can cause CMT, and several more under investigation. The type of genetic mutation you have may determine what symptoms of CMT you have and when symptoms begin. […] To diagnose CMT, your neurologist will use a comprehensive suite of diagnostic tests. This may include: A complete nervous system exam, A questionnaire about your family history, A blood test to identify genetic mutations, Nerve conduction studies to assess the electrical signals in your nerves, Electromyography to see how your nerves and muscles communicate, A nerve biopsy, which involves looking at a sample of your nervous tissue under a microscope.

• #10 Charcot-Marie-Tooth Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562163/

  If there is a family history of CMT with a known variant, genetic testing should be performed for that variant. If the results are not diagnostic and NGS is available and affordable, CMT large-panel genetic testing should be performed. […] Electromyography (EMG) and NCV testing are crucial for confirming the diagnosis of neuropathy and distinguishing between demyelinating and axonal types of CMT. […] The key parameters measured are distal latencies, amplitudes, and velocities of motor and sensory nerves. […] The median NCV of 38 m/s is commonly used to differentiate demyelinating from axonal types of CMT. […] Establishing the genetic diagnosis is crucial for ongoing genetic counseling, reproductive planning, and considering the patient for potential new therapies in research.

• #11 Charcot-Marie-Tooth Disease Workup: Laboratory Studies, Imaging Studies, Electrodiagnostic Studies

  https://emedicine.medscape.com/article/1232386-workup

  Electromyography (EMG) and nerve conduction studies should be performed first if CMT disease is suggested. […] Harding and Thomas criteria for diagnosing CMT 1 include a median motor NCV of less than 38 m/s, with compound motor action potential (CMAP) and amplitude of at least 0.5 mV. […] Nerve biopsy rarely is indicated for the diagnosis of CMT disease, especially with the availability of genetic testing. […] Histologic findings vary according to the type of CMT disease present.

• #12

  https://www.nhs.uk/conditions/charcot-marie-tooth-disease/diagnosis/

  If you have early symptoms of Charcot-Marie-Tooth disease (CMT), your GP will ask about your symptoms and may carry out a physical examination. […] During a physical examination, your GP will look for evidence of the condition, such as muscle weakness, poor or absent reflexes, and foot deformities, such as high arches or flat feet. […] If CMT is suspected, you may be referred to a doctor who specialises in treating conditions of the nervous system (a neurologist) for further testing. […] A nerve conduction test measures the strength and speed of signals transmitted through your peripheral nerves, the network of nerves that run from the brain and spinal cord to and from the rest of the body, such as the limbs and organs. […] Some types of CMT cause a distinctive change in the pattern of electrical activity that can be detected by an EMG.

• #13 Charcot-Marie-Tooth Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562163/

  If there is a family history of CMT with a known variant, genetic testing should be performed for that variant. If the results are not diagnostic and NGS is available and affordable, CMT large-panel genetic testing should be performed. […] Electromyography (EMG) and NCV testing are crucial for confirming the diagnosis of neuropathy and distinguishing between demyelinating and axonal types of CMT. […] The key parameters measured are distal latencies, amplitudes, and velocities of motor and sensory nerves. […] The median NCV of 38 m/s is commonly used to differentiate demyelinating from axonal types of CMT. […] Establishing the genetic diagnosis is crucial for ongoing genetic counseling, reproductive planning, and considering the patient for potential new therapies in research.

• #14 Charcot-Marie-Tooth Disease Workup: Laboratory Studies, Imaging Studies, Electrodiagnostic Studies

  https://emedicine.medscape.com/article/1232386-workup

  Electromyography (EMG) and nerve conduction studies should be performed first if CMT disease is suggested. […] Harding and Thomas criteria for diagnosing CMT 1 include a median motor NCV of less than 38 m/s, with compound motor action potential (CMAP) and amplitude of at least 0.5 mV. […] Nerve biopsy rarely is indicated for the diagnosis of CMT disease, especially with the availability of genetic testing. […] Histologic findings vary according to the type of CMT disease present.

• #15 Charcot-Marie-Tooth Syndrome | Doctor

  https://patient.info/doctor/charcot-marie-tooth-disease

  Diagnosing Charcot-Marie-Tooth disease (investigations)7 […] Exclude other causes of neuropathy with tests that may include: […] Blood tests: FBC, TFTs, LFTs, VDRL, vitamin B12, folate, antinuclear antibodies, creatine kinase. […] Serum and urine protein electrophoresis. […] Muscle biopsy. […] Cerebrospinal fluid (CSF) examination. […] MRI of the brain and spinal cord. […] Genetic studies – family history may be falsely negative due to the variable expression of mutations. First-degree relatives may also undertake clinical and sometimes electrophysiological testing to ascertain the inheritance pattern. […] Electrophysiology: nerve conduction studies show: […] Low conduction velocities (38 m/s in upper limb motor nerves) in peripheral demyelinating neuropathy such as CMT1 and CMT4.

• #16 Charcot-Marie-Tooth disease – Diagnosis & treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/charcot-marie-tooth-disease/diagnosis-treatment/drc-20350522

  During the physical exam, your doctor may check for: […] Your doctor may also recommend the following tests, which can help provide information about the extent of your nerve damage and what may be causing it. […] Nerve conduction studies. These tests measure the strength and speed of electrical signals transmitted through your nerves. […] Electromyography (EMG). A thin needle electrode is inserted through your skin into the muscle. […] Nerve biopsy. A small piece of peripheral nerve is taken from your calf through an incision in your skin. […] Genetic testing. These tests, which can detect the most common genetic defects known to cause Charcot-Marie-Tooth disease, are done with a blood sample. […] Have you or others in your family had genetic testing to confirm the diagnosis?

• #17 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Charcot-Marie-Tooth-Disease-Diagnosis.aspx

  Electromyography (EMG) is a diagnostic test that involves the placement of an electrode on the skin of the patient to measure the electrical activity of the muscles. This is useful for the diagnosis of CMT because there are significant changes in the muscular activity in affected individuals. […] Blood tests may also be taken to check for the presence of gene mutations that are known to cause CMT. This is useful to detect the disease in most individuals who have known mutations, but there are also several unidentified causative genes. Therefore, an individual may be diagnosed with the condition without positive genetic testing results. […] Rarely, a nerve biopsy may be required in the diagnostic process, particularly when other testing methods have proven to be inconclusive. This involves obtaining a sample from a peripheral nerve in the leg, which is examined for physical changes under a microscope.

• #18 Understanding CMT: Symptoms & Management

  https://www.cmtausa.org/understanding-cmt/what-is-cmt/

  CMT CAN BE DIFFICULT FOR A DOCTOR TO DIAGNOSE, especially when there is no established family history of CMT. According to CMTA Centers of Excellence CMT specialists, to diagnose CMT, one must meet the appropriate clinical picture: high arches, reduced sensation especially in the lower limbs, reduced or absent reflexes, frequent tripping, difficulty writing, abnormal nerve conduction study (NCS) results, and any number of other CMT symptoms. […] CMT SHARES SYMPTOMS WITH OTHER CONDITIONS, such as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), Vitamin B12 deficiency, G6PD-deficiency associated blood disorders, etc. Part of diagnosing CMT is ruling out conditions that are potentially treatable, and especially those that can be relatively easy to treat, such as Vitamin B12-deficiency.

• #19 Charcot-Marie-Tooth Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562163/

  Charcot-Marie-Tooth (CMT) disease is the most common inherited neuromuscular disorder, characterized by progressive weakness of the extremities due to peripheral nerve damage. […] The diagnosis of CMT, which involves clinical evaluation, electrophysiology, imaging, and genetic testing, is essential for patient education and counseling, initiating a rehabilitation program, and considering therapeutic trials. […] Screen patients with suspected Charcot-Marie-Tooth disease using comprehensive clinical evaluation, electrophysiology, and genetic testing to confirm diagnosis and assess disease severity. […] Genetic testing is the standard for establishing a conclusive diagnosis, providing medical counseling, aiding reproductive planning, and selecting patients for therapeutic trials and research.

• #20 Guidelines for molecular diagnosis of Charcot-Marie-Tooth disease | Neurología (English Edition)

  https://www.elsevier.es/es-revista-neurologia-english-edition–495-articulo-guidelines-for-molecular-diagnosis-charcot-marie-tooth-S2173580812000417

  Guidelines for molecular diagnosis of Charcot-Marie-Tooth disease […] This paper is aimed at performing a nosological review of the disease, emphasising the guidelines for its molecular diagnosis. […] In the great majority of CMT cases, mutations involve a reduced number of genes, namely: for CMT1, PMP22, GJB1 and MPZ; for CMT2, MFN2 and GJB1; for CMT4, GDAP1, and NDRG1, HK1 and SH3TC2 (gypsies); for AR-CMT2, GDAP1; and for DI-CMT, GJB1 and MPZ. […] The first step is to establish whether the patient suffers a hereditary neuropathy. […] The next step should be a neurophysiological examination, including determination of the MCV and SCV (sensory conduction velocity) in at least 3 nerves. […] Currently, nerve biopsy is reserved for cases where there are problems in the differential diagnosis with other hereditary neuropathies (e.g. amyloidosis). […] Given the enormous and growing number of pathogenic genes involved in CMT and the considerable cost of molecular studies, it is clear that genetic testing must be specifically targeted. […] The diagnosis of CMT should be based on an adequate clinical, family and neurophysiological study.

• #21 Charcot-Marie-Tooth disease and related hereditary polyneuropathies: Molecular diagnostics determine aspects of medical management | Genetics in Medicine

  https://www.nature.com/articles/gim200614

  Purpose: An evidence-based approach was used to determine the frequency distribution of genes contributing to the Charcot-Marie-Tooth (CMT) disease phenotype. […] Testing for the CMT1A duplication (i.e., duplication of PMP22) alone yields an accurate molecular diagnosis in approximately half of all patients. […] If one further specifies the clinical type (demyelinating vs. axonal), the yield of detecting a molecular defect increases to 75% to 80% in the demyelinating or CMT1 group with a screening test that evaluates for CMT1A duplication/hereditary neuropathy with liability to pressure palsies deletion and GJB1 point mutations. […] Molecular testing for inherited neuropathy is clinically available. […] The detection of point mutations in any of the CMT-causing genes requires sequencing of the appropriate genes, and lack of clustering of mutations necessitates screening the entire coding region.

• #22 Diagnostic laboratory testing for Charcot Marie Tooth disease (CMT): the spectrum of gene defects in Norwegian patients with CMT and its implications for future genetic test strategies | BMC Medical Genetics | Full Text

  https://bmcmedgenet.biomedcentral.com/articles/10.1186/1471-2350-14-94

  Due to the clinical and genetic heterogeneity, the low sensitivity of genetic testing for CMT2 and scarcity of clinical data, CMT as a group represents a number of challenges for diagnostic laboratories. […] We aimed at investigating to which extent available clinical and family information is influencing the success in the identification of disease causing variants. […] The test algorithm was shortened with one or more of the requested analyses in 137/435 investigated index cases. […] The mutation detection rate among these 59 cases was 22.0% (3 MPZ, 1 NEFL, 7 GJB1and 2MFN2mutations). […] The majority (95.8%) of the positive molecular genetic findings were either duplication of the PMP22region or sequence variants in either one of theMPZ,GJB1orMFN2genes. […] We suggest a pragmatic two-tier approach to genetic testing in CMT; the first tier should be used by referral centres receiving blood or DNA samples, not patients.

• #23 Diagnostic laboratory testing for Charcot Marie Tooth disease (CMT): the spectrum of gene defects in Norwegian patients with CMT and its implications for future genetic test strategies | BMC Medical Genetics | Full Text

  https://bmcmedgenet.biomedcentral.com/articles/10.1186/1471-2350-14-94

  Current genetic test algorithms for Charcot Marie Tooth (CMT) disease are based on family details and comprehensive clinical and neurophysiological data gathered under ideal conditions for clinical assessment. […] Our objective was therefore to perform a retrospective evaluation of the data given in laboratory request forms and to assess their quality and applicability with regard to the recommended algorithms for CMT diagnostics. […] Diagnostic testing of index patients was requested in 435 of the 549 cases. Seventy-two (16.6%) positive molecular genetic findings were made. […] We suggest a simplified algorithm intended for referral centres, dealing with DNA/blood samples, which involves the assessment of age at onset and neurophysiological data followed by testing of four genes; PMP22(duplication),MPZ,GJB1andMFN2.

• #24 Charcot-Marie-Tooth Disease: Updates in Diagnosis and Treatment Guidelines Pertaining to the Lower Extremity and Case Study

  https://clinmedjournals.org/articles/ijfa/international-journal-of-foot-and-ankle-ijfa-7-080.php?jid=ijfa

  The authors advocate for referral to a neurogenetics center or genetic counselor specializing in neurogenetics. The following protocol is recommended by GeneReviews: […] Step 1: Single gene testing for PMP22 duplication/deletion as first line testing. Greater than 50% of CMT is secondary to PMP22 duplication. Should PMP22 duplication/deletion testing be normal, reflex to step 2. […] Step 2: Multigene testing for the seven next most commonly involved genes (i.e., GDAP1, GJB1, HINT1, MFN2, MPZ, SH3CT2, and SORD) is most likely to be revealing of underlying genetic cause at the most reasonable cost. Should that be unrevealing, reflex to step 3. […] Step 3: Comprehensive genomic testing may be warranted. Exome sequencing is often used, however genomic sequencing is possible. […] CMT currently has no cure. Based on the authors experience, careful examination of the patient is critical to identifying deformity and determination of whether it is reducible or rigid. Accurate assessment will help guide treatment options. Patients can often lessen the severity of their symptoms through physical therapy, bracing, and in some cases surgery. Pain medications may also be helpful for individuals coping with unmanageable pain. […] Should conservative treatment fail, surgical management may be considered. The goal in all treatment options is to provide a stable framework for gait and preservation of joint mobility when possible.

• #25 Charcot-Marie-Tooth Disease Workup: Laboratory Studies, Imaging Studies, Electrodiagnostic Studies

  https://emedicine.medscape.com/article/1232386-workup

  All routine laboratory tests are normal in individuals with Charcot-Marie-Tooth (CMT) disease. However, special genetic tests are available for some types of CMT disease. […] DNA-based testing for the PMP22 duplication (CMT 1A) is widely available and detects more than 98% of patients with CMT 1A. […] Genetic testing for CMT 1B is performed primarily on a research basis, but it is available from a few commercial laboratories. […] Molecular genetic testing is also available clinically for these. […] About 90% of cases of CMT X can be detected by means of molecular genetic testing of the GJB1 (Cx32) gene. Such testing is clinically available. […] Genetic testing currently is not available for other types of CMT disease. […] A study by Millere et al found that plasma neurofilament light chain (NfL) concentrations were higher in CMT patients than in healthy control subjects and suggested that NfL might prove useful as a biomarker in the setting of suspected CMT disease.

• #26 Charcot-Marie-Tooth disease and related hereditary polyneuropathies: Molecular diagnostics determine aspects of medical management | Genetics in Medicine

  https://www.nature.com/articles/gim200614

  Molecular diagnostic screening in clinical diagnostic laboratories, with a less clinically defined cohort, also revealed the CMT1A duplication as the most frequently observed mutation in patients with hereditary neuropathy. […] The combination of PMP22 duplication and GJB1 mutation testing identifies the candidates for clinical trials, and if these trials reveal novel treatment options, ultimately identifies those who may benefit from treatment. […] If patients with the demyelinating form are tested as a group, the diagnostic yield increases to 75% to 80% by initially performing just PMP22 duplication and GJB1 mutation analyses as a screening test. […] Although inherited peripheral neuropathy represents a heterogeneous group of disorders at the molecular level, testing for a few genes/mutations yields an accurate molecular diagnosis in more than half of patients. […] The population-based studies suggest that in patients with the demyelinating phenotype, MPZ and PMP22 mutations are the next most common after PMP22 duplication and GJB1 mutations.

• #27 Charcot-Marie-Tooth disease testing

  https://www.rcpa.edu.au/Manuals/RCPA-Manual/Pathology-Tests/C/Charcot-Marie-Tooth-disease-testing

  Specimen: 5-10 ml blood in EDTA tube. […] Method: Multiplex ligase-dependant probe amplification (MLPA) or single nucleotide polymorphism (SNP) microarray to detect copy number variations (duplication/deletion) in PMP22. […] Application: Used in conjunction with neurophysiological studies to diagnose Charcot-Marie-Tooth (CMT) type 1A and Hereditary neuropathy with liability to pressure palsies (HNPP, also called Tomaculous neuropathy). […] Interpretation: The first line test (MLPA or SNP microarray) detects the 1.5Mb duplication in the gene PMP22 which is responsible for the most common form of CMT, namely CMT type 1A. […] The absence of a copy number variation in PMP22 does not exclude the diagnosis, as there are more than 80 different genes associated with CMT. […] Patients with peripheral neuropathy where no copy number variation is detected in PMP22 may be referred for consideration of gene panel testing using massively parallel sequencing.

• #28 Invitae Charcot-Marie-Tooth Disease Comprehensive Panel | Test catalog | Invitae

  https://www.invitae.com/us/providers/test-catalog/test-03201

  The Invitae Charcot-Marie-Tooth Disease Comprehensive Panel analyzes genes associated with Charcot-Marie-Tooth disease (CMT), a group of hereditary neuropathies characterized by progressive muscle weakness and sensory loss in the arms and legs. […] Genetic testing of these genes may help confirm a clinical diagnosis, help predict disease prognosis and progression, facilitate early detection of symptoms, inform family planning and genetic counseling, or promote enrollment in clinical trials. […] Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS). […] Based on validation study results, this assay achieves 99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions 15bp in length, and exon-level deletions and duplications. […] This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient’s constitutional genome.

• #29 Quest’s Athena Diagnostics Launches NGS Panel Test for Charcot-Marie-Tooth Disease | GenomeWebRSS FeedsVisit GenomeWeb on TwitterVisit GenomeWeb on LinkedIn

  https://www.genomeweb.com/sequencing/quests-athena-diagnostics-launches-ngs-panel-test-charcot-marie-tooth-disease

  Quest Diagnostics has launched a next-generation sequencing-based panel to diagnose Charcot-Marie-Tooth disease, as well as a handful of Sanger-based tests for other rare neurological disorders, which were developed through its Athena Diagnostics business. […] The Charcot-Marie-Tooth panel includes 23 genes associated with the disorder, including the full exons of each gene and splice sites. Average coverage is 100-fold and turnaround time is three to four weeks. […] Physicians who want to order the NGS-based Charcot-Marie-Tooth panel will also have the ability to customize their order. […] Additionally, all patients will first be screened for deletions and duplications to the PMP22 gene using multiplex ligation-dependent probe amplification. […] Deletions and duplications to PMP22 are „one of the highest indicators at getting this condition,” explained Steve Becker, executive director of Quest’s neurology segment solutions.

• #30 Charcot-Marie-Tooth Disease Panel| Revvity

  https://www.revvity.com/test/Charcot-Marie-Tooth-Disease-Panel-D4037

  This test analyzes genes associated with Charcot-Marie-Tooth disease. […] Charcot-Marie-Tooth (CMT) disease, also known as hereditary motor and sensory neuropathy, is a group of inherited neurological disorders characterized by progressive damage to the peripheral nerves, leading to muscle weakness, sensory loss, and various neurological symptoms. […] This gene sequencing panel includes both sequencing and deletion/duplication (CNV) analysis for all coding regions of the included genes (unless otherwise noted). All analysis is performed utilizing next-generation sequencing (NGS) technology. All variants are classified according to American College of Genetics and Genomics (ACMG) guidelines. […] Sequencing is performed on genomic DNA using an Agilent targeted sequence capture method to enrich for the exome.

• #31 Charcot-Marie-Tooth Disease Panel| Revvity

  https://www.revvity.com/test/Charcot-Marie-Tooth-Disease-Panel-D4037

  This assay cannot detect variants in regions of the exome that are not covered, such as deep intronic, promoter and enhancer regions, areas containing large numbers of tandem repeats, and variants in mitochondrial DNA. […] Copy number variation (CNV) analysis detects deletions and duplications; in some instances, due to the size of the exons, sequence complexity, or other factors, not all CNVs may be analyzed or may be difficult to detect.

• #32 Charcot–Marie–Tooth Disease DiagnosisEnvelope icon

  https://charcot-marie-toothnews.com/charcot-marie-tooth-disease-diagnosis/

  Results are interpreted considering the patient’s symptoms, physical exam, family history, and the results of other laboratory tests. A negative result does not exclude CMT, as an unidentified gene may be missed by DNA sampling. […] This test helps detect the degeneration of nerve fibers and myelin, the insulating sheath that surrounds nerve fibers and allows proper transmission of electric signals. The test primarily measures the speed at which an electric signal travels along nerve fibers. […] Results of nerve conduction studies can help identify which CF type a patient has, as CMT types with myelin degeneration have lower conduction velocity than those characterized by degeneration of nerve fibers. […] Nerve conduction studies often are performed with EMG, a method that measures the electrical activity between muscles and specialized nerve cells called motor neurons. Together, these procedures help determine if a problem exists in nerves or muscles.

• #33 Charcot-Marie-Tooth disease – Diagnosis & treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/charcot-marie-tooth-disease/diagnosis-treatment/drc-20350522

  During the physical exam, your doctor may check for: […] Your doctor may also recommend the following tests, which can help provide information about the extent of your nerve damage and what may be causing it. […] Nerve conduction studies. These tests measure the strength and speed of electrical signals transmitted through your nerves. […] Electromyography (EMG). A thin needle electrode is inserted through your skin into the muscle. […] Nerve biopsy. A small piece of peripheral nerve is taken from your calf through an incision in your skin. […] Genetic testing. These tests, which can detect the most common genetic defects known to cause Charcot-Marie-Tooth disease, are done with a blood sample. […] Have you or others in your family had genetic testing to confirm the diagnosis?

• #34 Charcot-Marie-Tooth Disease Workup: Laboratory Studies, Imaging Studies, Electrodiagnostic Studies

  https://emedicine.medscape.com/article/1232386-workup

  Electromyography (EMG) and nerve conduction studies should be performed first if CMT disease is suggested. […] Harding and Thomas criteria for diagnosing CMT 1 include a median motor NCV of less than 38 m/s, with compound motor action potential (CMAP) and amplitude of at least 0.5 mV. […] Nerve biopsy rarely is indicated for the diagnosis of CMT disease, especially with the availability of genetic testing. […] Histologic findings vary according to the type of CMT disease present.

• #35

  https://www.nhs.uk/conditions/charcot-marie-tooth-disease/diagnosis/

  Genetic testing involves taking a blood sample and testing it for defective genes known to cause CMT. […] Most people with CMT should be able to have their diagnosis confirmed by genetic testing and find out exactly which type of CMT they have. […] In a small number of cases where other tests have been inconclusive, a test called a nerve biopsy may be carried out. […] CMT can cause physical changes to the shape of the nerve, which can be seen under a microscope. […] If you have recently been diagnosed with CMT, you may find it useful to: take all the time you need do not rush into making important decisions about your health. […] Couples with a family history of CMT who are thinking of having a baby can be referred to a genetics specialist for advice. […] The main tests that can be carried out during pregnancy to check if a baby will develop certain types of CMT are: chorionic villus sampling (CVS) where a small sample of placenta is removed from the womb and tested for known CMT genes, usually during weeks 11 to 14 of pregnancy. […] If these tests show that your child is likely to have CMT, you can discuss with your genetic counsellor whether you want to continue the pregnancy or have a termination (abortion). […] For some couples at risk of having a child with CMT, pre-implantation genetic diagnosis (PGD) may be an option.

• #36 Diagnosis – Charcot-Marie-Tooth UK

  https://www.cmt.org.uk/cmt-and-you/diagnosis/

  If you and your GP think you may have Charcot-Marie-Tooth Disease, you will be referred to a doctor who specialises in problems of the nerves, known as a neurologist. […] The neurologist will follow a number of steps to confirm whether you have the condition or not. […] Your doctor will take a standard patient history, including a family history. […] Next, you will be given a neurological examination. […] If there is an established family history of CMT where a family member has already received a confirmed genetic diagnosis, then clinical assessment alone may be all that is needed to make a diagnosis. […] Sometimes you will be offered a genetic test for the most common form of CMT (type 1A). […] In the UK, the next stage of diagnosis will be a genetic test to try to confirm which type of CMT you have. […] In very rare circumstances, when there is doubt about the precise diagnosis, nerve biopsy may be advised.

• #37 Charcot–Marie–Tooth Disease DiagnosisEnvelope icon

  https://charcot-marie-toothnews.com/charcot-marie-tooth-disease-diagnosis/

  A nerve biopsy is less common in CMT diagnosis and used mostly when the results of all other methods are inconclusive. In a nerve biopsy, a small incision is made to remove a small piece of peripheral nerve for analysis. Generally, the biopsy is taken from the calf of the lower leg. […] Here, doctors may find particular abnormalities in the peripheral nerves, such as abnormal myelination and nerve fiber degeneration, that are specific to disease type.

• #38 Understanding CMT: Symptoms & Management

  https://www.cmtausa.org/understanding-cmt/what-is-cmt/

  CMT CAN BE DIFFICULT FOR A DOCTOR TO DIAGNOSE, especially when there is no established family history of CMT. According to CMTA Centers of Excellence CMT specialists, to diagnose CMT, one must meet the appropriate clinical picture: high arches, reduced sensation especially in the lower limbs, reduced or absent reflexes, frequent tripping, difficulty writing, abnormal nerve conduction study (NCS) results, and any number of other CMT symptoms. […] CMT SHARES SYMPTOMS WITH OTHER CONDITIONS, such as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), Vitamin B12 deficiency, G6PD-deficiency associated blood disorders, etc. Part of diagnosing CMT is ruling out conditions that are potentially treatable, and especially those that can be relatively easy to treat, such as Vitamin B12-deficiency.

• #39 Orphanet: Charcot-Marie-Tooth disease type 1

  https://www.orpha.net/en/disease/detail/65753

  Charcot-Marie-Tooth disease type 1 (CMT1) is a group of autosomal dominant demyelinating peripheral neuropathies characterized by distal weakness and atrophy, sensory loss, foot deformities, and slow nerve conduction velocity. […] Diagnosis of CMT1 is based on progressive peripheral motor and sensory neuropathy; slow nerve conduction velocity (NCV) with motor NCV de novo mutations). Genetic testing is the gold standard for diagnosis. […] Differential diagnosis includes other genetic neuropathies, especially X-linked CMT, autosomal dominant CMT2, CMT4, and hereditary neuropathy with liability to pressure palsies. CMT1 identification may be challenging when there is no family history and acquired demyelinating neuropathies must also be taken into account. […] Preimplantation genetic diagnosis may be an option for families in which the pathogenic variant has been identified. […] Transmission is autosomal dominant with complete penetrance and genetic counseling is recommended.

• #40 Charcot-Marie-Tooth Syndrome | Doctor

  https://patient.info/doctor/charcot-marie-tooth-disease

  Diagnosing Charcot-Marie-Tooth disease (investigations)7 […] Exclude other causes of neuropathy with tests that may include: […] Blood tests: FBC, TFTs, LFTs, VDRL, vitamin B12, folate, antinuclear antibodies, creatine kinase. […] Serum and urine protein electrophoresis. […] Muscle biopsy. […] Cerebrospinal fluid (CSF) examination. […] MRI of the brain and spinal cord. […] Genetic studies – family history may be falsely negative due to the variable expression of mutations. First-degree relatives may also undertake clinical and sometimes electrophysiological testing to ascertain the inheritance pattern. […] Electrophysiology: nerve conduction studies show: […] Low conduction velocities (38 m/s in upper limb motor nerves) in peripheral demyelinating neuropathy such as CMT1 and CMT4.

• #41

  https://www.nhs.uk/conditions/charcot-marie-tooth-disease/diagnosis/

  Genetic testing involves taking a blood sample and testing it for defective genes known to cause CMT. […] Most people with CMT should be able to have their diagnosis confirmed by genetic testing and find out exactly which type of CMT they have. […] In a small number of cases where other tests have been inconclusive, a test called a nerve biopsy may be carried out. […] CMT can cause physical changes to the shape of the nerve, which can be seen under a microscope. […] If you have recently been diagnosed with CMT, you may find it useful to: take all the time you need do not rush into making important decisions about your health. […] Couples with a family history of CMT who are thinking of having a baby can be referred to a genetics specialist for advice. […] The main tests that can be carried out during pregnancy to check if a baby will develop certain types of CMT are: chorionic villus sampling (CVS) where a small sample of placenta is removed from the womb and tested for known CMT genes, usually during weeks 11 to 14 of pregnancy. […] If these tests show that your child is likely to have CMT, you can discuss with your genetic counsellor whether you want to continue the pregnancy or have a termination (abortion). […] For some couples at risk of having a child with CMT, pre-implantation genetic diagnosis (PGD) may be an option.

• #42 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Charcot-Marie-Tooth-Disease-Diagnosis.aspx

  As CMT can be caused by a number of known gene mutations, expectant couples with a family history of the disease may wish to find out if their baby is likely to be affected. These tests are carried out during pregnancy to determine whether a baby has inherited the defective genes and their risk for developing CMT. […] Chorionic villus sampling (CVS) is a test that involves taking a sample of the placenta from the womb, usually between weeks 11 and 14 of the pregnancy. The sample is then examined for the presence of gene mutations associated with CMT in a laboratory. […] Another test that can be used to diagnose CMT in a fetus is amniocentesis. This test involves taking a sample of the amniotic fluid, usually between weeks 15 to 20 of the pregnancy. The sample is then examined for genetic mutations that are indicative of CMT.

• #43 Understanding CMT: Symptoms & Management

  https://www.cmtausa.org/understanding-cmt/what-is-cmt/

  CMT CAN BE DIFFICULT FOR A DOCTOR TO DIAGNOSE, especially when there is no established family history of CMT. According to CMTA Centers of Excellence CMT specialists, to diagnose CMT, one must meet the appropriate clinical picture: high arches, reduced sensation especially in the lower limbs, reduced or absent reflexes, frequent tripping, difficulty writing, abnormal nerve conduction study (NCS) results, and any number of other CMT symptoms. […] CMT SHARES SYMPTOMS WITH OTHER CONDITIONS, such as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), Vitamin B12 deficiency, G6PD-deficiency associated blood disorders, etc. Part of diagnosing CMT is ruling out conditions that are potentially treatable, and especially those that can be relatively easy to treat, such as Vitamin B12-deficiency.

• #44 A Search for Undiagnosed Charcot-Marie-Tooth Disease Among Patients Re | CLEP

  https://www.dovepress.com/a-search-for-undiagnosed-charcot-marie-tooth-disease-among-patients-re-peer-reviewed-fulltext-article-CLEP

  In a recent study based on data from the Danish National Patients Registry (DNPR), we reported the prevalence of Charcot-Marie-Tooth disease (CMT) in Denmark to be 22.5 per 100.000. This prevalence is most likely a minimum estimate, as many cases of CMT may be misdiagnosed or remain undiagnosed due to the heterogeneous nature of the disorder. The aim of this study was to investigate the possible number of undiagnosed CMT cases among patients registered with unspecified polyneuropathy (UP) diagnoses in the DNPR. […] We found that 21.5% (95% CI 13.1% 32.2%) of the cases in the random sample fulfilled our criteria for CMT. This estimate increases the prevalence of CMT in Denmark with 3.6 per 100,000 (95% CI 2.4% 5.5%). […] Our study shows that a considerable number of patients may have CMT but remain undiagnosed, and confirms that the previously reported prevalence of CMT is probably underestimated.

• #45 A Search for Undiagnosed Charcot-Marie-Tooth Disease Among Patients Re | CLEP

  https://www.dovepress.com/a-search-for-undiagnosed-charcot-marie-tooth-disease-among-patients-re-peer-reviewed-fulltext-article-CLEP

  The aim of the present study was to investigate whether the prevalence of CMT in Denmark is higher than previously reported by estimating the proportion of possible CMT cases among patients diagnosed with unspecified polyneuropathy (UP) diagnoses in the DNPR. […] The main finding of this study is that 21.5% (95% CI 13.1%32.2%) of a selected cohort of patients diagnosed with UP may have undiagnosed CMT. This supports our hypothesis; that using only CMT diagnoses from the DNPR will lead to an underestimation of the prevalence of CMT in Denmark. […] In a selected group of patients diagnosed with an unspecified polyneuropathy diagnosis in the DNPR, we found that 21.5% could have undiagnosed CMT. This corresponds to an increase in the prevalence of CMT in Denmark with 3.6 per 100,000 (95% CI 2.4%-5.5%): from 22.5 per 100,000 (95% CI 21.2%-23.7%) as reported previously to 26.1 per 100,000 (95% CI 24.1%-28.0%). This study supports the hypothesis, that many patients with CMT are undiagnosed.

• #46 Charcot-Marie-Tooth Disease (CMT) and SMA: What Are the Differences? | mySMAteam

  https://www.mysmateam.com/resources/charcot-marie-tooth-disease-and-sma-what-are-the-differences

  CMT diagnosis requires a thorough family medical history and physical exam. Genetic testing is not usually used to diagnose CMT because of the large number of possible gene mutations that can cause the disease. Additional tests for nerve conduction velocity are needed to help determine the type of CMT. […] Because so many different genes can cause CMT, genetic testing is not as useful for diagnosis as with SMA.

• #47 What is Charcot Marie Tooth (CMT) Disease? | CMT Research Foundation

  https://cmtrf.org/what-is-cmt-disease/

  Testing for Charcot-Marie-Tooth disease involves a comprehensive approach that integrates clinical evaluation, family history, and various diagnostic tests. This process is essential for diagnosing CMT and determining the specific subtype a patient may have. […] Initially, a detailed medical history and neurological examination are conducted to assess symptoms consistent with peripheral nerve damage, a hallmark of CMT, and usually includes electrophysiological tests, such as nerve conduction studies and electromyography. These tests measure the electrical activity transmitted through the nerves and in the muscle and can help distinguish between the primary subtypes of CMT. […] Given the genetic nature of CMT, genetic testing has become a key step in confirming the diagnosis. This test can detect the presence of gene mutations associated with the various forms of CMT. Genetic testing not only facilitates precise diagnosis, but also allows for more accurate treatment strategies and more understanding of the inheritance pattern. Having a genetic diagnosis also allows for more contribution to the advancement of drug development research.

• #48 Charcot-Marie-Tooth Disease (CMT): Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/6009-charcot-marie-tooth-disease-cmt

  It usually takes a combination of methods for a healthcare provider to determine the exact type of CMT you have and determine your cases severity. The methods include a physical and neurological exam, lab tests, imaging and other diagnostic tests. Theyll also ask questions about your family medical history and your history and life circumstances. […] The following tests are most likely with CMT: Electromyogram (especially nerve conduction tests). Genetic testing. Spinal tap (lumbar puncture) to test cerebrospinal fluid. Magnetic resonance imaging (MRI). Ultrasound. Evoked potentials (especially for CMT subtypes that affect your hearing and vision). Nerve biopsy. […] Charcot-Marie-Tooth disease isnt a condition you can self-diagnose because it requires specific medical tests. Some of the symptoms of CMT can also happen with other conditions, some of which are very serious. Because of that, you should always talk to a healthcare provider to learn if you have this condition and what you should do to manage it.

• #49 Guidelines for molecular diagnosis of Charcot-Marie-Tooth disease | Neurología (English Edition)

  https://www.elsevier.es/es-revista-neurologia-english-edition–495-articulo-guidelines-for-molecular-diagnosis-charcot-marie-tooth-S2173580812000417

  Guidelines for molecular diagnosis of Charcot-Marie-Tooth disease […] This paper is aimed at performing a nosological review of the disease, emphasising the guidelines for its molecular diagnosis. […] In the great majority of CMT cases, mutations involve a reduced number of genes, namely: for CMT1, PMP22, GJB1 and MPZ; for CMT2, MFN2 and GJB1; for CMT4, GDAP1, and NDRG1, HK1 and SH3TC2 (gypsies); for AR-CMT2, GDAP1; and for DI-CMT, GJB1 and MPZ. […] The first step is to establish whether the patient suffers a hereditary neuropathy. […] The next step should be a neurophysiological examination, including determination of the MCV and SCV (sensory conduction velocity) in at least 3 nerves. […] Currently, nerve biopsy is reserved for cases where there are problems in the differential diagnosis with other hereditary neuropathies (e.g. amyloidosis). […] Given the enormous and growing number of pathogenic genes involved in CMT and the considerable cost of molecular studies, it is clear that genetic testing must be specifically targeted. […] The diagnosis of CMT should be based on an adequate clinical, family and neurophysiological study.

• #50 Charcot-Marie-Tooth Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK562163/

  If there is a family history of CMT with a known variant, genetic testing should be performed for that variant. If the results are not diagnostic and NGS is available and affordable, CMT large-panel genetic testing should be performed. […] Electromyography (EMG) and NCV testing are crucial for confirming the diagnosis of neuropathy and distinguishing between demyelinating and axonal types of CMT. […] The key parameters measured are distal latencies, amplitudes, and velocities of motor and sensory nerves. […] The median NCV of 38 m/s is commonly used to differentiate demyelinating from axonal types of CMT. […] Establishing the genetic diagnosis is crucial for ongoing genetic counseling, reproductive planning, and considering the patient for potential new therapies in research.

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