Diagnosis of Charcot-Marie-Tooth Disease
Diagnosis of CMT begins with a standard medical history, family history, and neurological examination. Individuals will be asked about the nature and duration of their symptoms and whether other family members have the disease. During the neurological examination a physician will look for evidence of muscle weakness in the individual's arms, legs, hands, and feet, decreased muscle bulk, reduced tendon reflexes, and sensory loss. Doctors look for evidence of foot deformities, such as high arches, hammertoes, inverted heel, or flat feet. Other orthopedic problems, such as mild scoliosis or hip dysplasia, may also be present. A specific sign that may be found in people with CMT1 is nerve enlargement that may be felt or even seen through the skin. These enlarged nerves, called hypertrophic nerves, are caused by abnormally thickened myelin sheaths.

If CMT is suspected, the physician may order electrodiagnostic tests. This testing consists of two parts: nerve conduction studies and electromyography (EMG). During nerve conduction studies, electrodes are placed on the skin over a peripheral motor or sensory nerve. These electrodes produce a small electric shock that may cause mild discomfort. This electrical impulse stimulates sensory and motor nerves and provides quantifiable information that the doctor can use to arrive at a diagnosis. EMG involves inserting a needle electrode through the skin to measure the bioelectrical activity of muscles. Specific abnormalities in the readings signify axon degeneration. EMG may be useful in further characterizing the distribution and severity of peripheral nerve involvement.

Genetic testing is available for some types of CMT and results are usually enough to confirm a diagnosis. In addition, genetic counseling is available to assist individuals in understanding their condition and plan for the future.

If all the diagnostic work-up in inconclusive or genetic testing comes back negative, a neurologist may perform a nerve biopsy to confirm the diagnosis.  A nerve biopsy involves removing a small piece of peripheral nerve through an incision in the skin.  This is most often done by removing a piece of the nerve that runs down the calf of the leg.  The nerve is then examined under a microscope.  Individuals with CMT1 typically show signs of abnormal myelination.  Specifically, "onion bulb" formations may be seen which represent axons surrounded by layers of demyelinating and remyelinating Schwann cells.  Individuals with CMT1 usually show signs of axon degeneration.  Recently, skin biopsy has been used to study unmyelinated and myelinated nerve fibers in a minimally invasive way, but their clinical use in CMT has not yet been established.