What are the symptoms and management of Charcot-Marie-Tooth disease?

Symptoms and Management of Charcot-Marie-Tooth Disease

Charcot-Marie-Tooth disease (CMT) is best managed through a comprehensive rehabilitation approach including strengthening exercises, orthotic devices, and regular monitoring, as there is currently no curative drug therapy available. 1

Clinical Presentation

CMT is characterized by:

• Primary symptoms:

  • Distal limb muscle wasting and weakness (length-dependent axonal degeneration)
  • Distal sensory loss
  • Skeletal deformities (particularly in feet)
  • Abnormal deep tendon reflexes 2

• Common physical findings:

  • Pes cavus (high arched feet)
  • Foot drop
  • Digit contractures
  • Difficulty with ambulation and grasping objects 3
  • Predominantly distal muscular atrophy of the limbs 4

• Less common manifestations:

  • Late onset presentations
  • Cranial nerve involvement
  • Upper limb predominance
  • Autonomic nervous system dysfunction
  • Severe scoliosis
  • Early-onset glaucoma 2

Diagnostic Approach

1. Electrodiagnostic studies (EDX) are essential for:

   • Distinguishing between demyelinating (CMT1) and axonal (CMT2) types
   • Guiding genetic testing strategy 1

2. Genetic testing should follow a tiered approach:

   • Start with PMP22 duplication/deletion testing for classic CMT symptoms and family history
   • Testing should be guided by clinical phenotype, EDX features, and inheritance pattern 1

3. Distribution of CMT subtypes:

   • CMT1A (PMP22 gene duplication): 70%
   • CMTX (Cx32/GJB1 mutations): 12%
   • CMT2 (MFN2 mutations): 33% of CMT2 cases
   • Other less common subtypes 1

Management Strategies

Rehabilitation and Exercise

• Implement a comprehensive exercise program including:
  • Strengthening exercises
  • Stretching
  • Core stability training
  • Balance and resistance training
  • Aerobic exercises 1

Orthotic and Footwear Management

• Provide appropriate footwear:
  • Extra wide or deep shoes
  • Custom-molded shoes for severe deformities 1
• Orthotic devices to maintain function and prevent complications 1

Monitoring and Prevention

• Regular foot inspection for injuries, especially in areas with sensory loss
• Monitor skin temperature and restrict activity during inflammation
• Regular assessment of:
  • Muscle strength
  • Balance
  • Functional capacity
  • Development of foot deformities and pressure points 1

Surgical Intervention

Consider surgical intervention when:

• Foot/ankle joint instability is present
• Deformities with high risk of developing ulcers exist
• Pain cannot be adequately managed with conservative measures 1

Potential Complications

• Progression to foot deformities
• Development of ulcers at pressure points
• Infections at sites of sensory loss
• Reactivation of the disease process 1

Emerging Therapies

While no curative treatments currently exist, promising research includes:

• Ascorbic acid (vitamin C) showed improvement in CMT1A mouse models
• Progesterone antagonists improved neuropathy in CMT1A rat models 5

Clinical Pearls

• CMT is often first apparent in infancy but may have variable onset and progression 4
• The disease is genetically heterogeneous with multiple inheritance patterns (autosomal dominant, autosomal recessive, X-linked) 4
• Careful distinction from acquired neuropathies is important, as CMTX can sometimes present with asymmetric and nonhomogeneous conduction slowing similar to inflammatory neuropathies 2
• CMT should be distinguished from diabetic Charcot, as CMT is a genetic condition requiring different long-term management strategies 1