Charcot-Marie-Tooth disease (CMT) is one of the most common inherited neurological disorders. Overall CMT affects approximately 1 in 2,500 people. CMT, also known as hereditary motor and sensory neuropathy or peroneal muscular atrophy, comprises a group of disorders that affect peripheral nerves. The peripheral nerves lie outside the brain and spinal cord and supply the muscles and sensory organs in the limbs. Symptoms usually begin gradually sometime in adolescence, early adulthood or middle age with initial signs of weakness in the lower leg muscles, affecting the patient’s ability to walk and causing frequent falls. As the disease progresses, muscle atrophy may occur in the feet and hands. The condition affects an equal number of mem and women. Currently there is no cure for CMT, but pain killers, physical therapy, occupational therapy, braces, other orthopedic devices and surgery can help relieve some of the symptoms.
CMT is classically divided into two major types, a demyelinating form (CMT1 & CMT4) and an axonal form (CMT2). CMT3, also known as Dejerine-Sottas syndrome, is a severe type of CMT in which symptoms begin in infancy or early childhood. An X-linked variant also occurs (CMTX). Approximately 60% of all CMT patients have CMT1. About 70% of these patients have CMT1A (prevalence 1:5000) which is associated with an autosomal dominant 1.4 Mb duplication on chromosome 17p11.2 that includes the peripheral myelin protein 22 gene (PMP22) expressed predominantly in the compact myelin of Schwann cells. Another 5-10% of CMT1 cases have CMT1B, which is associated with mutations in the major myelin protein zero gene (MPZ) that cause demyelination. The CMT1A subtype is by far the most common form of CMT, followed by CMTX, CMT1B and CMT2A. Together these four subtypes account for more than 85% of all genetic diagnoses in CMT.