Charcot-Marie-Tooth disease

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Charcot-Marie-Tooth disease


Autonomic nervous system disorders

Horner syndrome

Orthostatic hypotension


Charcot-Marie-Tooth disease


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USMLE® Step 1 questions

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High Yield Notes

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Charcot-Marie-Tooth disease

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USMLE® Step 1 style questions USMLE

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A 14-year-old boy is brought to the clinic by his mother due to complaints of weakness and numbness in the lower extremities. The patient has sprained both ankles on multiple occasions over the past year while playing soccer due to difficulty running, which has progressively worsened. The patient has not had any recent infections or diarrhea. The patient's family lives in a new home built 3 years ago. The patient’s mother reports the patient was adopted at the age of 3, and she is unsure of his biological family’s history. Vital signs are within normal limits. Distal calf muscle atrophy is noted. There is loss of proprioception and vibratory sensation in both feet. Ankle reflexes are 1+ bilaterally. An image of the patient’s foot is shown below. This patient’s neurological dysfunction is most likely caused by which of the following?  

Image reproduced from Wikimedia Commons

External References

First Aid








Autosomal dominant disease

Charcot-Marie-Tooth disease p. 542

Charcot-Marie-Tooth disease p. 542


Charcot-Marie-Tooth disease is named after three neurologists - Jean-Martin Charcot, Pierre Marie and Howard Henry Tooth.

The disease is actually not a single disease, but a group of related diseases that are progressive hereditary disorders of peripheral nervous system.

Said differently, these disorders are inherited, worsen over time, and affect both sensory and motor nerve cells.

Broadly speaking, the nervous system consists of two parts, the central nervous system, and the peripheral nervous system.

The central nervous system consists of the brain and the spinal cord, and the peripheral nervous system includes the nerves that fan out from the central nervous system and connect it with the skin, muscles, organs, and exocrine glands.

Now, zooming in to a neuron, each one is made up of three main parts.

The dendrites, which are little branches that receive signals from other neurons, the soma or cell body, which has all of the neuron’s main organelles, and the axon, which transmits the signal to the next neuron in the series.

Myelin is the protective sheath that surrounds the axons of the peripheral neurons, allowing them to quickly send electrical impulses.

And this myelin is produced by Schwann cells, which are a group of cells that support neurons.

There are multiple forms of Charcot-Marie-Tooth disease and all of them are related to the defective production of proteins in either the myelin sheath or the neuron’s axon.

Regardless of the part of the neuron that’s affected, signals fail to reach their target tissues, and this can affect both sensory and motor peripheral neurons.

The most common forms of Charcot-Marie-Tooth disease are CMT1 and CMT2, both of which are autosomal dominant diseases.

CM T1 is caused by mutations in the PMP22 and MPZ genes, which encode proteins that are part of the myelin sheath made by the Schwann cells.

Loss of myelin slows down transmission of electrical impulses through the nerves.

Over time, Schwann cells try to replace the lost myelin.

As a result, under a microscope, there’s often onion bulb formation, which is when an axon is surrounded by layers of new myelin with underlying damaged layers of myelin.


Charcot-Marie-Tooth disease (CMT) is a neuromuscular disorder that progressively affects the peripheral nervous system. It can lead to progressive lower extremity weakness but can also affect the other organs. CMT symptoms vary from person to person, but can include weakness or numbness in the feet and legs, problems with balance and coordination, difficulty walking, and pain in affected areas. In some cases, CMT can also cause problems with bladder or bowel function, breathing, and heart rate.


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  4. "CURRENT Medical Diagnosis and Treatment 2020" McGraw-Hill Education / Medical (2019)
  5. "Neurological dysfunction and axonal degeneration in Charcot-Marie-Tooth disease type 1A" Brain (2000)
  6. "Neuropathic pain in Charcot-Marie-tooth disease" Archives of Physical Medicine and Rehabilitation (1998)
  7. "Hereditary motor and sensory neuropathies." Journal of Medical Genetics (1991)

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