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

Management of Charcot-Marie-Tooth Disease

Charcot-Marie-Tooth disease management is entirely supportive, focusing on rehabilitation therapy, orthotic devices, and surgical correction of skeletal deformities, as there are currently no approved disease-modifying drugs available. 1, 2, 3

Core Treatment Approach

Rehabilitation Therapy

• Intensive rehabilitation programs should be implemented for patients with mild to moderate CMT, consisting of 2-4 hours daily, 5 days per week, for 3-week cycles 4
• The program should include manual treatments, strengthening exercises, stretching, core stability training, balance and resistance training, aerobic exercises, and tailored self-care training 4
• Short-term functional improvements occur with intensive rehabilitation, but benefits diminish by 12 months, necessitating repeated treatment cycles 4
• Regular follow-up should be scheduled according to disease severity to reassess functional status and adjust therapy 1

Orthotic Management

• Ankle-foot orthoses (AFOs) should be prescribed to address foot drop and improve gait stability 5
• Custom footwear should be provided to accommodate pes cavus deformity and prevent pressure ulcers 5

Surgical Intervention

• Surgical correction of skeletal deformities (particularly pes cavus, claw toes, and ankle instability) should be considered when conservative measures fail to maintain function 1, 3, 5

Symptomatic Management

Pain and Fatigue

• Pain management strategies should be implemented as needed, though specific agents are not defined in current guidelines 1
• Fatigue should be addressed through energy conservation techniques and pacing strategies 4
• Cramp management may require stretching protocols and hydration optimization 4

Emerging Therapies (Not Yet Approved)

While no disease-modifying therapies are currently available, several approaches are under investigation:

Gene-Based Therapies

• Gene silencing strategies (ASO, siRNA, CRISPR-Cas9) targeting PMP22 overexpression in CMT1A are in development 2, 3
• Gene therapy for CMT2S has reached clinical trial stage, representing the most advanced gene therapy approach 3
• Gene addition therapy for recessive forms with loss-of-function mutations is being explored 2

Pharmacological Approaches

• PXT3003 is in phase III trials for CMT1A, representing the most advanced drug candidate 2
• Neuregulin pathway modulators show promise for both hypo- and hypermyelinating neuropathies 2
• HDAC6 inhibitors have demonstrated improved axonal transport in animal models 2

Critical Clinical Pitfalls

Do not confuse CMT with Charcot neuro-osteoarthropathy (CNO) - these are entirely different conditions despite sharing the "Charcot" name. The evidence provided includes extensive guidelines on CNO (a diabetic foot complication), which is unrelated to CMT (an inherited peripheral neuropathy) 6, 7, 8

Key Distinctions

• CMT is an inherited peripheral neuropathy causing progressive weakness and sensory loss 5
• CNO is an inflammatory bone/joint condition in diabetic patients with neuropathy 6
• Treatment approaches are completely different between these conditions

Monitoring and Follow-Up

• Muscle strength assessment should be performed regularly using standardized scales 4
• Walking speed and balance testing should be conducted to track functional decline 4
• Nerve conduction studies and genetic testing establish diagnosis but are not routinely repeated for monitoring 5
• Disease course is variable due to genetic and phenotypic heterogeneity, requiring individualized monitoring intervals 5

Current Limitations

There is no established best practice for rehabilitation frequency, intensity, or duration despite rehabilitation being the primary treatment modality 5. The evidence suggests benefits are temporary, requiring ongoing intervention cycles rather than one-time treatment 4.