CharcotMarieTooth

Charcot-Marie-Tooth disease (CMT) is a group of inherited neurological disorders that affect peripheral nerves, causing progressive weakness and atrophy in distal limbs. It is the most common inherited peripheral neuropathy, with an estimated prevalence of 1 in 2,500 to 1 in 5,000 people.

CMT is genetically heterogeneous, with many subtypes caused by mutations in different genes. The most common form, CMT1A, results from a duplication of the PMP22 gene and is usually autosomal dominant. Other forms involve MPZ, MFN2, GJB1, PRX, GDAP1, and several other genes. Inheritance patterns include autosomal dominant, autosomal recessive, and X-linked.

Symptoms typically begin in adolescence or early adulthood, though onset can be later or earlier. People develop foot deformities such as pes cavus, hammertoes, and a drop foot with steppage gait, leading to frequent falls. Distal muscle weakness and sensory loss in the feet and hands, reduced reflexes, and fatigue are common. Disease progression is variable, and some individuals experience relatively slow progression over decades.

Diagnosis combines clinical examination with nerve conduction studies and electromyography to distinguish demyelinating from axonal forms, followed by genetic testing to identify the subtype. Management is multidisciplinary and supportive, as there is no cure. Treatments focus on maintaining mobility and independence: physical and occupational therapy, ankle-foot orthoses, orthopedic surgery for foot deformities, pain management, and respiratory support when needed. Genetic counseling is available, and prognosis ranges from mild to wheelchair dependence in severe cases.