Charcot-Marie-Tooth (CMT) disease is the most common genetic form of motor and sensory neuropathy, affecting approximately 1 in every 2500 individuals in the US.1 There are over 100 causative genes known to be responsible for the various forms of CMT, comprising a large spectrum of neuropathic disorders that are classified based on their effects on nerve cells and inheritance patterns.1 Recently, investigators have identified mutations that cause inherited neuropathies in at least 17 different genes, and chromosomal loci have been identified in more than 25 additional genes.2
The most prominent forms are type 1 (CMT1), the demyelinating form, and type 2 (CMT2), the axonal form. CMT1 is an autosomal dominant variant that presents abnormalities in the myelin that covers nerve cells, which slows the transmission of nerve impulses and compromises the health of the nerve fiber, causing decreased sensation in extremities and muscle strength.2
Type 2 CMT does not affect the speed of transmission of nerve impulses but reduces the action potential amplitude that thereby affects muscle strength. CMT is not fatal but can be debilitating and can negatively impact quality of life. Due to its dominant inheritance pattern, a thorough family history can be an initial screening tool for CMT to facilitate early identification and decrease disease progression.2
Signs and Symptoms of CMT
There are several physical examination findings that can increase the suspicion for CMT. Awareness of the 3 patterns in which a patient can present with CMT can lead to the appropriate diagnosis.
- The first presentation includes an insidious, progressive onset of bilateral leg weakness and sensory loss with an onset in patients aged 10 to 30 years. Eventually, the distal weakness leads to foot drop and decreased or absent deep tendon reflexes in all extremities. Patients can later develop weakness and changes in sensation in their hands and feet bilaterally.3
- The second CMT presentation involves a much earlier onset of symptoms in younger children and includes delayed walking (15 months) and clumsiness due to toe-walking, and difficulty picking up their feet when walking, often leading to falls.3
- The third presentation has a much later onset, at roughly age 40, with signs and symptoms similar to the first 2 presentations.3
One of the most common signs of CMT is a foot abnormality known as pes cavus. This is an increase in the degree of arch in the foot, often due to an imbalance between the intrinsic muscles of the foot and leg.4 Hammertoes are the second most common foot abnormality and are also due to atrophy of intrinsic muscles in the feet, causing them to curl up.
Patients who present with foot abnormalities may have difficulty flexing the foot or walking on their heels on physical examination, possibly precipitating a steppage gait that results in the patient taking higher than normal steps, while increasing the risk of ankle injuries and falls.4-6
Given the prevalence of symptoms of peripheral neuropathy, weakness in extremities, gait imbalance, and grip strength, the neurologic examination is an essential part of the patient interview. Once the signs and symptoms are identified, it is important for clinicians to complete further testing to definitively diagnose CMT in these patients.