Charcot‐Marie‐Tooth Disease: An Overview of Genotypes, Phenotypes, and Clinical Management Strategies

Abstract

Charcot-Marie-Tooth (CMT) disease, which encompasses several hereditary motor and sensory neuropathies, is one of the most common neuromuscular disorders. Our understanding of the molecular genotypes of CMT and the resultant clinical and electrophysiological phenotypes has increased greatly in the past decade. Characterized by electrodiagnostic studies into demyelinating (type 1) and axonal (type 2) forms, subsequent genetic testing often provides an exact diagnosis of a specific subtype of CMT. These advancements have made diagnostic paradigms fairly straightforward. Still, the nature and extent of neuromuscular disability is often complex in persons with CMT, and no curative treatments are yet available. Genotypically homologous animal models of CMT have improved exploration of disease-modifying treatments, of which molecular genetic manipulation and stem cell therapies appear to be the most promising. Research is also needed to develop better rehabilitative strategies that may limit disease burden and improve physical performance and psychosocial integration. Clinical management should be multidisciplinary, including neurologists, physiatrists, neurogeneticists, neuromuscular nurse practitioners, and orthopedists, along with physical and occupational therapists, speech-language pathologists, orthotists, vocational counselors, social workers, and other rehabilitation clinicians. Goals should include maximizing functional independence and quality of life while minimizing disability and secondary morbidity.

Management of Charcot–Marie–Tooth disease: improving long-term care with a multidisciplinary approach

“…It has been used as primary endpoints in therapeutic trials, and in natural history studies as discussed in the “Physical therapy and orthoses” section. 13 , 16 , 20 , 34 , 47 – 51 The CMT examination score can be used in patients without electrodiagnostic data, and is simply the sum of non-neurophysiologic data on the CMTNS. 41 The CMT pediatric examination score is another physician determined age-adjusted functional assessment score designed to assess disability in children.…”

Long term AAV2/9-mediated silencing of PMP22 prevents CMT1A disease in rats and validates skin biomarkers as treatment outcome measure

“…Indeed, several peripheral nerve diseases impair the myelin sheath leading to reduced nerve conduction velocity, nerve dysfunction, muscle waste, limb extremities deformations and walking and sensory problems [6]. The large majority of patients suffering from hereditary diseases of peripheral nerves, namely Charcot-Marie-Tooth diseases (CMT), have defects in the myelin sheath formation, function or maintenance [10]. The most common of these myelin-related CMT diseases is CMT1A (prevalence 5-10/10000) [47].…”

Trk receptor signaling and sensory neuron fate are perturbed in human neuropathy caused by Gars mutations

“…Although lifespan is usually unaffected, patients display characteristic muscle weakness and wasting predominantly in the extremities, leading to difficulty walking, foot deformities, and reduced dexterity (2). CMT is traditionally divided into type 1/ demyelinating CMTs that display loss of peripheral nerve myelin causing reduced nerve conduction velocity (NCV), type 2/axonal CMTs typified by axon loss with relatively normal NCVs, and intermediate CMTs that share clinical features of CMT1 and -2 (1).…”