What is Charcot-Marie-Tooth (CMT) disease?

Charcot-Marie-Tooth Disease (CMT)

Charcot-Marie-Tooth disease is a genetically heterogeneous group of inherited peripheral neuropathies characterized by progressive degeneration of peripheral nerves, resulting in distal muscle weakness, sensory loss, and foot deformities. 1, 2

Clinical Characteristics

• Primary Features:

  • Progressive distal muscle weakness and atrophy
  • Sensory loss in a "glove and stocking" distribution
  • Foot deformities (particularly cavus foot)
  • High stepping gait with frequent trips or falls
  • Areflexia (absent deep tendon reflexes)
  • Onset typically in infancy or childhood 1, 2

• Secondary Features:

  • Skeletal deformities (hammertoes, prominent metatarsal heads)
  • Distal muscle wasting, particularly in lower extremities
  • Abnormal gait patterns
  • Digit contractures 1, 3

Classification

CMT can be classified by several methods:

1. Pattern of Inheritance:

   • Autosomal dominant
   • Autosomal recessive
   • X-linked 2, 3

2. Electrophysiological Findings:

   • CMT1: Demyelinating form (slow nerve conduction velocities)
   • CMT2: Axonal form (normal or slightly reduced conduction velocities)
   • Intermediate forms 3, 4

3. Genetic Mutations:

   • CMT1A (most common): PMP22 gene duplication
   • CMTX1: Second most common
   • Other subtypes based on specific gene mutations 5, 4

Diagnostic Approach

• Clinical Evaluation:

  • Assess for distal muscle weakness and atrophy
  • Evaluate sensory loss patterns
  • Examine for foot deformities, especially cavus foot
  • Evaluate gait pattern
  • Check family history (often positive) 1, 3

• Electrophysiological Studies:

  • Nerve conduction studies to distinguish demyelinating from axonal forms
  • Uniform and diffuse slowing in CMT1A
  • Sometimes asymmetric slowing in CMTX 4

• Imaging:

  • Plain X-rays to assess foot deformities
  • MRI when clinical suspicion remains high despite normal X-rays 1

• Genetic Testing:

  • Based on clinical and electrophysiological findings
  • Start with testing for PMP22 duplication (CMT1A) as most common form 3, 4

Management Approaches

• Rehabilitation:

  • Structured exercise program including:
    • Strengthening exercises
    • Stretching
    • Balance training
    • Core stability training
    • Aerobic exercises 1

• Orthotic Management:

  • Custom footwear/orthoses to accommodate foot deformities
  • Below-knee customized devices for joint instability or severe deformity 1

• Supportive Care:

  • Regular foot inspection for injuries
  • Avoidance of high-impact activities
  • Use of assistive devices when needed 1

• Emerging Treatments:

  • Gene therapy approaches in development (silencing, replacement, or editing)
  • Currently no FDA-approved disease-modifying treatments 6

Differential Diagnosis

• Chronic inflammatory demyelinating polyneuropathy (CIDP)

  • CMT lacks conduction blocks typical in CIDP
  • CMT shows diffuse nerve enlargement on ultrasound vs. asymmetric in CIDP
  • Some CMT subtypes may respond to immunomodulatory therapy, complicating diagnosis 5

• Diabetic neuropathy (particularly Charcot neuro-osteoarthropathy)

  • Different etiology despite some similar presentations 1

Monitoring and Follow-up

• Regular assessment of muscle strength and functional capacity
• Monitoring for development of new foot deformities
• Surveillance for pressure points that could lead to skin breakdown
• Evaluation of need for adaptive equipment 1

CMT is a lifelong condition requiring ongoing management. While there are currently no disease-modifying treatments available, proper supportive care can significantly improve quality of life and prevent complications.