Is Charcot-Marie-Tooth (CMT) disease a progressive disease?

Charcot-Marie-Tooth Disease Progression

Yes, Charcot-Marie-Tooth (CMT) disease is definitively a progressive neurological disorder characterized by gradual worsening of muscle weakness, atrophy, and sensory deficits over time. 1, 2

Disease Characteristics and Progression

• CMT is a genetically heterogeneous group of inherited peripheral neuropathies with a prevalence of approximately 1:2,500 people 1
• The disease shows measurable progression over time, with studies demonstrating an average increase of 0.686 points per year on the CMT Neuropathy Score (CMTNS) 2
• CMT is characterized by progressive distal muscle weakness and atrophy, sensory loss, and foot deformities that worsen over time 1, 3
• The progression typically begins in childhood or adolescence but can present at any age, with symptoms gradually worsening throughout life 1
• If not properly diagnosed and managed, the progressive nature of CMT leads to increasing disability with gait abnormalities, foot drop, and steppage gait 1, 3

Clinical Manifestations of Progressive Disease

• The disease typically begins with distal muscle weakness and atrophy, particularly in the lower limbs, creating a characteristic "stork leg" appearance 1, 4
• Sensory deficits develop in a "glove and stocking" distribution and worsen over time 1, 4
• Bilateral pes cavovarus (high arch with inverted heel) is the most common foot deformity and can become more pronounced with disease progression 1
• Deep tendon reflexes decrease or become absent as the disease progresses 1
• The rate of progression may increase with age, suggesting an accelerating disease course in later years 2

Diagnostic Considerations

• Electrodiagnostic studies are essential for classification into demyelinating (CMT1) or axonal (CMT2) subtypes, which may have different rates of progression 1, 4
• Genetic testing provides definitive diagnosis with 100% specificity for established pathogenic mutations 1, 4
• The most common subtype, CMT1A (PMP22 gene duplication), accounts for approximately 70% of CMT1 cases and shows measurable progression that can be tracked with clinical scales 1, 2
• CMT should be differentiated from acquired neuropathies and Charcot arthropathy, which may present with similar symptoms but have different causes and progression patterns 5, 4

Monitoring Disease Progression

• The CMT Neuropathy Score (CMTNS) and Neuropathy Impairment Score (NIS) are validated tools for measuring disease progression 2
• The CMTNS combines symptoms, signs, and electrophysiology, while the NIS is based solely on neurological examination; both scales show measurable changes over time 2
• Regular monitoring of disease progression is important for assessing treatment efficacy and planning appropriate interventions 2
• The progressive nature of CMT supports the feasibility of clinical trials aimed at slowing disease progression using these scales as outcome measures 2

Common Pitfalls in Management

• Failure to recognize CMT as a progressive disease may lead to inadequate monitoring and management 1, 2
• Misdiagnosis as acquired neuropathies (diabetic, toxic, or inflammatory) can result in inappropriate treatment approaches 1, 4
• Overlooking the progressive nature of CMT may delay implementation of supportive measures to address worsening symptoms 1
• Asymmetric and nonhomogeneous conduction slowing in some CMT subtypes (particularly CMTX) can mimic acquired inflammatory neuropathies, leading to diagnostic confusion 1, 6