Charcot-Marie-Tooth Disease

Suspect CMT in a length-dependent motor and sensory neuropathy with distal weakness, distal sensory loss, absent deep-tendon reflexes, and foot or hand deformity, particularly when the course is slowly progressive or the pedigree suggests autosomal dominant, X-linked, or recessive inheritance. Document age at onset, walking milestones, progression, prior foot and tendon procedures, focal compression palsies, and a three-generation pedigree before ordering molecular testing. Nature+2NatureCharcot–Marie–Tooth disease and related neuropathies | Nature Reviews Disease PrimersScienceDirectClinical practice guidelines for the diagnosis and management of Charcot-Marie-Tooth diseasePubMedCharcot-Marie-Tooth Disease - StatPearls - NCBI Bookshelf

Do not use the absence of family history to exclude CMT. PMP22 duplications can arise de novo, and a patient with a sporadic, uniformly demyelinating sensorimotor polyneuropathy should still undergo CMT1A-directed testing. PubMed+1PubMedDiagnosis of Charcot-Marie-Tooth DiseasePubMedPMP22 related neuropathies: Charcot-Marie-Tooth disease type 1A and Hereditary Neuropathy with liability to Pressure Palsies

Escalate evaluation for an acquired neuropathy when the presentation is not a stable, length-dependent inherited pattern, particularly with prominent asymmetry, recurrent stepwise deterioration, or other features not explained by the family phenotype. Electrodiagnostic testing is the required next discriminator because it separates demyelinating from axonal patterns and helps distinguish generalized inherited neuropathy from focal pressure-related disease. ScienceDirect+1ScienceDirectClinical practice guidelines for the diagnosis and management of Charcot-Marie-Tooth diseasePubMedPMP22 related neuropathies: Charcot-Marie-Tooth disease type 1A and Hereditary Neuropathy with liability to Pressure Palsies

Obtain a formal neurophysiological study after clinical suspicion of CMT. The study should establish whether the neuropathy is predominantly demyelinating or axonal and should assess motor and sensory nerves rather than relying on clinical subtype labels alone. ScienceDirect+1ScienceDirectClinical practice guidelines for the diagnosis and management of Charcot-Marie-Tooth diseaseNatureClinical implications of genetic advances in Charcot–Marie–Tooth disease | Nature Reviews Neurology

For a classical phenotype, upper-extremity motor nerve conduction velocity (MNCV) of greater than 15 to 35 m/s is categorized as slow; MNCV of 15 m/s or less identifies a severely slow subgroup associated with delayed walking in the cited testing algorithm. These categories can direct phenotype-specific testing but do not encompass every genetic cause of CMT. PubMedPubMedCharcot Marie Tooth (CMT) Subtypes and Genetic Testing Strategies - PMC

In suspected HNPP, electrophysiology supports the clinical diagnosis by showing mild conduction slowing and increased motor latencies; findings must be interpreted with the compression-palsy history because chronic repeated focal injury can overlap clinically with CMT1. PubMedPubMedDiagnosis of Charcot-Marie-Tooth Disease

Order separate PMP22 deletion/duplication analysis as the first test for a proband with CMT unless the chosen laboratory explicitly includes validated PMP22 copy-number analysis in its panel. The assay differs from methods used in many multigene panels, and the PMP22 duplication at 17p11.2 accounts for as much as 50% of CMT. PubMedPubMedCharcot-Marie-Tooth Hereditary Neuropathy Overview - GeneReviews® - NCBI Bookshelf

For autosomal dominant or sporadic demyelinating hereditary neuropathy, screen first for chromosome 17p duplication encompassing PMP22. If negative, obtain a disease-specific next-generation sequencing panel that includes known CMT genes rather than serial single-gene testing when available. Nature+1NatureClinical implications of genetic advances in Charcot–Marie–Tooth disease | Nature Reviews NeurologyPubMedPMP22 related neuropathies: Charcot-Marie-Tooth disease type 1A and Hereditary Neuropathy with liability to Pressure Palsies

If a multigene panel is nondiagnostic in a familial case, consider whole-exome sequencing; published algorithms reserve this escalation for familial cases after negative PMP22 testing and panel-level evaluation. PubMedPubMedPMP22 related neuropathies: Charcot-Marie-Tooth disease type 1A and Hereditary Neuropathy with liability to Pressure Palsies Whole-genome sequencing has also identified pathogenic variation in CMT, but its role should be individualized to unresolved cases and the laboratory's ability to detect relevant variant classes. NEJM+1NEJMWhole-Genome Sequencing in a Patient with Charcot ...NatureClinical implications of genetic advances in Charcot–Marie–Tooth disease | Nature Reviews Neurology

Interpret the molecular result alongside phenotype and electrophysiology. A genetic finding can establish diagnosis, support counseling and reproductive planning, and identify patients for research or therapeutic trials; pretest counseling should address these implications before testing. PubMedPubMedCharcot-Marie-Tooth Disease - StatPearls - NCBI Bookshelf

There is no established pharmacologic disease-modifying treatment for any CMT subtype. Do not defer symptomatic and functional care while genetic testing is pending: initiate multidisciplinary management focused on individualized exercise, muscle-strength training, orthotic devices, symptom relief, and surveillance for associated complications. Nature+1NatureCharcot–Marie–Tooth disease and related neuropathies | Nature Reviews Disease PrimersScienceDirectClinical practice guidelines for the diagnosis and management of Charcot-Marie-Tooth disease

Refer for rehabilitation assessment early, with individualized exercise guidance and orthotic adaptation targeted to the observed functional deficit. Strength training and orthoses are core rehabilitative approaches, and early intervention is intended to identify and improve functional limitations before fixed disability or deformity becomes more difficult to address. Nature+1NatureCharcot–Marie–Tooth disease and related neuropathies | Nature Reviews Disease PrimersScienceDirectClinical practice guidelines for the diagnosis and management of Charcot-Marie-Tooth disease

Obtain orthopedic assessment when foot deformity, gait limitation, progressive imbalance, or fixed musculoskeletal abnormality compromises function. Conservative surgical options, including tendon procedures, are part of orthopedic management and should be considered in the context of deformity and functional goals rather than delayed until advanced disability. ScienceDirect+1ScienceDirectClinical practice guidelines for the diagnosis and management of Charcot-Marie-Tooth diseaseScienceDirectCharcot Marie Tooth Disease

At longitudinal visits, reassess gait, distal strength, hand function, sensory loss, reflexes, foot structure, orthotic fit, falls or mobility limitations, and need for surgical reassessment. Standardized outcome measures include the CMT Neuropathy Score in adults and the Charcot-Marie-Tooth Pediatric Scale in children and adolescents. ScienceDirectScienceDirectCharcot Marie Tooth Disease

CMT associated with INF2 mutations has been reported with renal disease, particularly focal segmental glomerulosclerosis. In a patient with INF2-associated CMT or an unresolved CMT phenotype accompanied by proteinuric kidney disease, coordinate nephrology evaluation rather than attributing renal findings to nonspecific comorbidity. NEJMNEJMINF2 Mutations in Charcot–Marie–Tooth Disease with ...

Use syndrome-specific features to refine broad-panel results. The CMT genetic spectrum includes phenotypes with deafness, cataracts, retinitis pigmentosa, intellectual disability, and other non-neurologic manifestations; these findings should prompt focused review of genes and referral to the relevant specialty. PubMedPubMedCharcot-Marie-Tooth Hereditary Neuropathy Overview - GeneReviews® - NCBI Bookshelf

For HNPP, management must include prevention of recurrent mechanical nerve injury because focal dysfunction can follow minor compression or trauma. Repeated injuries may leave persistent deficits and produce clinical overlap with CMT1 over time. PubMedPubMedDiagnosis of Charcot-Marie-Tooth Disease