27th June 2023

Charcot-Marie-Tooth disease

Charcot-Marie-Tooth disease (CMT) is a spectrum of primary hereditary disorders causing both motor and sensory neuropathies which are slowly progressive. CMT are typically inherited in an autosomal dominant manner, although recessive and X-linked forms have been identified as well. There are a wide number of mutations known to cause CMT.

The most common form of CMT is CMT1a, which is associated with a duplication of the PMP22 gene leading to cumulative damage to the myelin sheath of the peripheral nerve axons. Patients with CMT1 will often present as teenagers or young adults with distal weakness and paraesthesia, causing frequent falls and ankle sprains. On examination, a gradual loss of proprioception and vibration can be identified. Over time, the atrophy will often lead to foot deformities such as pes cavus and hammer toes. Sleep apnoea is also commonly seen in these patients.

Patients with CMT2 commonly present in the second or third decade of life with distal symptoms such as reduced sensation and muscle weakness with atrophy. This form of the condition is typically associated with direct damage to the axons. Mutations to the MFN2 gene are associated with CMT2a, which is the most common cause of CMT2.

Electromyography with subsequent genetic testing is key to establishing a reliable diagnosis for most patients. Management remains supportive, with daily physiotherapy exercises and orthotics playing a central role in reducing the severity of deformities. Disability is known to increase with age, although symptom severity, age of onset and rate of progression vary considerably. Patients with CMT are also considered to be at higher risk from iatrogenic neurotoxicity, therefore, the disease is listed as a contra-indication to several drugs such as amiodarone, vincristine and tacrolimus.