Charcot-Marie-Tooth disease/Hereditary motor and sensory neuropathy

Charcot-Marie-Tooth disease (CMT), also known as hereditary motor and sensory neuropathy (HMSN) or peroneal muscular atrophy, is a group of inherited disorders that affect the peripheral nerves — the nerves outside the brain and spinal cord that control movement and sensation in the limbs. CMT is the most common inherited neurological disorder. It primarily affects the motor and sensory nerves, leading to progressive weakness and atrophy of the muscles in the feet, lower legs, hands, and forearms. Patients typically develop high-arched feet (pes cavus), hammertoes, difficulty walking, foot drop, and reduced sensation in the extremities. The disease is slowly progressive, and while most individuals remain ambulatory throughout life, some may require assistive devices such as braces or wheelchairs. CMT is classified into several major types based on electrophysiological findings, pathology, and genetic cause. CMT type 1 (demyelinating) is characterized by reduced nerve conduction velocities due to damage to the myelin sheath, while CMT type 2 (axonal) involves primarily axonal degeneration with relatively preserved conduction velocities. Other forms include CMT type 4 (autosomal recessive), CMT X-linked forms, and intermediate types. Over 100 genes have been identified as causes of CMT, with the most common being PMP22 duplication (CMT1A), mutations in GJB1 (CMTX1), MPZ, and MFN2. Inheritance patterns vary by subtype and include autosomal dominant, autosomal recessive, and X-linked forms. There is currently no cure for CMT. Treatment is supportive and focuses on maintaining function and quality of life. Physical therapy, occupational therapy, orthotic devices (such as ankle-foot orthoses), and pain management are cornerstones of care. Orthopedic surgery may be needed to correct foot deformities. Regular monitoring by a multidisciplinary team including neurologists, physiatrists, and orthopedic specialists is recommended. Several clinical trials are ongoing to investigate potential disease-modifying therapies, including gene therapy approaches and pharmacological agents targeting specific molecular pathways.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Charcot-Marie-Tooth disease/Hereditary motor and sensory neuropathy