What are the treatment options for a young adult diagnosed with Charcot-Marie-Tooth (CMT) disease?

Charcot-Marie-Tooth Disease Treatment

For a young adult with Charcot-Marie-Tooth disease, treatment focuses on supportive care including physical therapy, orthotic devices, and surgical correction of deformities when necessary, as no effective pharmacological disease-modifying therapy currently exists. 1, 2, 3

Current Management Approach

Supportive Care (Primary Treatment)

• Rehabilitation and physical therapy form the cornerstone of CMT management, aimed at maintaining muscle strength, preventing contractures, and preserving functional mobility 2, 3

• Occupational therapy helps patients adapt daily activities and maintain independence as the disease progresses 3

• Orthotic devices (ankle-foot orthoses/braces) are essential for correcting foot drop, improving gait stability, and preventing falls in patients with characteristic cavovarus foot deformity 1, 4

Symptomatic Treatment

• Pain management should be addressed with appropriate analgesics, as pain can significantly impact quality of life 3

• Fatigue management requires regular monitoring and supportive interventions, as fatigue is a common debilitating symptom 3

Surgical Intervention

• Surgical correction is indicated when foot and ankle deformities (particularly cavovarus deformity) cause instability, limit mobility, or fail to respond to conservative management 4

• Surgical options include:

  • Soft-tissue releases for contractures 4
  • Tendon transfers to rebalance muscle forces 4
  • Osteotomies to correct bony alignment 4
  • Arthrodesis (joint fusion) when necessary to create a stable plantigrade foot 4

Diagnostic Workup Required

• Electrophysiological studies are essential to classify the disease into demyelinating versus axonal subtypes, which guides genetic testing and prognosis 1

• Genetic testing provides definitive diagnosis with 100% specificity for established pathogenic mutations and should follow a stepwise approach based on clinical and electrophysiological findings 1

Emerging Therapies (Not Yet Available)

While no pharmacological treatments are currently approved, several investigational approaches are in development:

• PXT3003 is the most advanced compound for CMT1A (the most common subtype), currently in phase III clinical trials 5, 2

• Gene therapy strategies under investigation include:

  • Gene silencing techniques (ASO, siRNA, CRISPR-Cas9) to reduce PMP22 overexpression in CMT1A 2
  • Gene replacement therapy for recessive forms with loss-of-function mutations 2
  • Neuregulin pathway modulation for myelin thickness regulation 2

• HDAC6 inhibitors have shown promise in animal models by improving axonal transport 2

Critical Clinical Pitfall

Do not confuse CMT with Charcot neuro-osteoarthropathy (CNO) - these are entirely different conditions despite similar naming 6, 1. CMT is an inherited peripheral neuropathy presenting with "stork leg" appearance and sensory deficits in a glove-and-stocking distribution 1, while CNO is an inflammatory bone/joint condition occurring in diabetic patients with neuropathy 6, 7.

Follow-Up Strategy

• Regular monitoring is essential, with frequency determined by disease severity and rate of progression 3

• Serial assessments should evaluate motor function, sensory deficits, pain levels, and development of skeletal deformities 3, 8