Charcot-Marie-Tooth disease
The most common inherited peripheral neuropathy, comprising more than 70 genetic subtypes that cause slowly progressive distal weakness, sensory loss, areflexia, and foot deformity; diagnosis rests on nerve conduction studies and confirmatory genetic testing, and management is supportive since there is no disease-modifying drug therapy.
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What this article covers
- Overview
Definition: Charcot-Marie-Tooth (CMT) disease is a genetically heterogeneous group of more than 70 hereditary peripheral neuropathies in which peripheral nerve dysfunction is the sole or dominant clinical manifestation.
- Epidemiology
Most common inherited neuropathy: overall prevalence of roughly 1 in 2,500 people, making it more common than any single acquired hereditary neuromuscular disorder.
- Risk factors
Family history: autosomal dominant inheritance is most common (CMT1, most CMT2 subtypes); autosomal recessive (CMT4) and X-linked (CMT1X) patterns also occur and change the recurrence risk counseling.
- Pathophysiology
CMT1 (demyelinating): duplication of the PMP22 gene on chromosome 17 (CMT1A) or other myelin-protein mutations (CMT1B: MPZ) disrupt Schwann cell myelin structure and maintenance, causing segmental…
- Clinical features
Distal, symmetric, slowly progressive weakness: foot and ankle dorsiflexor weakness produces foot drop and a steppage gait; hand intrinsic weakness typically follows years later.
- Differential diagnosis
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP): also demyelinating but acquired, often asymmetric or proximal as well as distal, progresses over at least 8 weeks, has markedly…
- Diagnosis
Establishing the diagnosis: the combination of a compatible clinical phenotype (early-onset, slowly progressive, length-dependent, motor-predominant polyneuropathy with foot deformity) and…
- Management
No disease-modifying pharmacotherapy exists; management is supportive and centers on maximizing function and preventing secondary complications.
- Complications
Falls and fractures: from foot drop and impaired proprioception, a leading source of morbidity.
- Prognosis
Normal life expectancy in the great majority of subtypes, since CMT does not typically affect vital organ function.
- Prevention
No primary prevention of the genetic disease itself; prevention efforts target secondary complications and reproductive risk.
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