What is the management approach for Charcot-Marie-Tooth (CMT) disease?

Management of Charcot-Marie-Tooth Disease

Charcot-Marie-Tooth (CMT) disease requires a multidisciplinary supportive care approach focused on rehabilitation, orthotic management, and symptomatic treatment, as no disease-modifying pharmacologic therapies are currently available for clinical use. 1, 2, 3

Diagnostic Evaluation

Early diagnosis is critical to prevent deformity and optimize functional outcomes. 4

• MRI is the recommended advanced imaging modality for comprehensive assessment of bones, joints, ligaments, and tendons in CMT patients 4
• Genetic testing should be pursued to identify the specific CMT subtype, as over 80 genes are implicated in these inherited neuropathies 2
• Clinical assessment should focus on progressive muscular weakness, pes cavus deformity, loss of deep tendon reflexes, distal sensory loss, and gait impairment 5

Orthotic and Rehabilitation Management

Orthotic interventions should be implemented early to prevent progression of deformities. 4

Footwear and Orthotics

• Custom footwear with specialized insoles must be prescribed to ensure ongoing offloading and prevent skin breakdown 4
• Below-knee customized devices should be used when deformity and/or joint instability is present to optimize plantar pressure distribution 6

Rehabilitation Protocol

• Intensive rehabilitation programs (2-4 hours daily, 5 days per week, for 3 weeks) significantly improve short-term muscle strength and functional outcomes in mild to moderate CMT 5
• The rehabilitation program should include: manual treatments, strengthening exercises, stretching, core stability training, balance and resistance training, aerobic exercises, and tailored self-care training 5
• Physical and occupational therapy are essential components of long-term management 7

Important Caveat

• Improvements from intensive rehabilitation are not sustained at 1-year follow-up, suggesting the need for ongoing periodic rehabilitation interventions rather than one-time treatment 5

Symptomatic Management

• Pain and fatigue management should be addressed as these significantly impact quality of life 7, 2
• Analgesic medications may be necessary for neuropathic pain 2
• Mental health support should be integrated into care, as CMT impacts psychological well-being 7

Surgical Considerations

• Surgical treatment of skeletal deformities (particularly pes cavus) may be necessary when conservative management fails 5, 2
• Surgery should be considered for progressive deformities that interfere with ambulation or orthotic fitting 2

Multidisciplinary Team Composition

Optimal management requires coordination among: 7

• Neurologists for diagnosis and ongoing neurologic assessment 7
• Genetic counselors for family planning and genetic testing interpretation 7
• Physical and occupational therapists for functional training 7
• Physiatrists for rehabilitation oversight 7
• Orthotists for custom bracing and footwear 7
• Mental health providers for psychological support 7
• Orthopedic surgeons when surgical intervention is needed 2

Monitoring and Follow-up

• Regular follow-up according to disease severity is essential to monitor progression and adjust interventions 3
• Standardized clinical instruments should be used to assess disease progression and disability over time 7
• Patient-reported outcome measures should guide treatment adjustments 7

Emerging Therapies (Not Yet Available for Clinical Use)

While several investigational approaches are under development, no disease-modifying therapies have been proven effective in humans: 1, 3

• Gene therapy approaches (gene silencing for PMP22 in CMT1A, gene replacement for recessive forms) remain experimental 1, 3
• PXT3003 is in phase III trials for CMT1A but not yet approved 1
• Various molecular targets (neuregulin pathway, HDAC6 inhibitors, UPR modulators) show promise in animal models but lack human efficacy data 1, 3

Critical Pitfalls to Avoid

• Delayed diagnosis and referral to multidisciplinary care can lead to significant clinical deterioration and irreversible deformities 4
• Failing to implement early orthotic interventions allows preventable progression of foot deformities 4
• Treating rehabilitation as a one-time intervention rather than an ongoing periodic need leads to loss of functional gains 5