What is Charcot-Marie-Tooth Disease?

Charcot-Marie-Tooth disease, or CMT, is a progressive, degenerative disease involving the peripheral nerves that branch out from the brain and spinal cord to other parts of the body, including the arms, hands, legs and feet. CMT was discovered in 1886 by doctors—Jean-Marie Charcot, Pierre Marie, and Howard Henry Tooth—for whom the disorder was named.

Typically, the brain and nerves are constantly communicating with each other. But with CMT, the motor nerves (the nerves that control our muscles) and sensory nerves (the nerves that carry sensory information like pain and temperature to the brain) don’t work properly. They have trouble sending signals to and from the brain. This results in numbness, sensory loss, muscle weakness/atrophy and nerve degeneration. Over time, the muscles weaken and deteriorate.

Symptoms may begin as early as birth or during adulthood, and they become gradually worse over time. There are currently no treatments or cures for CMT.

What is Happening to My Body?

What Causes Charcot-Marie-Tooth Disease?

CMT is caused by genetic mutations. The type of CMT you have is determined by which gene is affected. CMT classification uses numbers (1, 2, 3, 4, 6) to depict type and letters (A, B, C …) to represent a subgroup within that type. An exception is type X (CMTX), which is passed down by X-linked inheritance.

Thanks to genetic testing and research there are more than 100 known genetic mutations that cause CMT, but most people have one of four most common types of CMT. These subtypes are:

• CMT1: Charcot-Marie-Tooth disease type 1 represents one of the most common hereditary types of neuropathy, highlighting the diversity of Charcot Marie Tooth types. This form of CMT affects the peripheral nerves with symptoms often manifesting in adolescence or early adulthood. CMT1 is primarily inherited in an autosomal dominant manner, making it a crucial subtype among the Charcot Marie Tooth disease types. Understanding the genetic underpinnings of CMT1 is essential for grasping how many types of Charcot-Marie-Tooth disease are there, offering insights into its diagnosis and management.
• CMT2: CMT2 is a significant subtype in the classification of Charcot Marie Tooth disease types, distinguished by its impact on the peripheral nerves. Unlike CMT1, CMT2 involves axonal damage that leads to muscle weakness and sensory loss, showcasing the complexity of types of Charcot Marie Tooth disorder. This form of CMT, highlighting how many types of Charcot Marie Tooth exist, is also inherited in patterns that can include autosomal dominant traits. The exploration of CMT2 enhances our understanding of Charcot-Marie-Tooth disease and its hereditary nature.
• CMT4: CMT4 is a rare and severe form of Charcot Marie Tooth disease, characterized by its autosomal recessive inheritance pattern. This subtype highlights the complexity and diversity among the Charcot Marie Tooth disease types, with significant implications for how many types of Charcot Marie Tooth disorder are recognized. CMT4’s impact on the peripheral nerves is profound, leading to early-onset symptoms that can significantly affect quality of life. As part of the broader spectrum of Charcot-Marie-Tooth disease, CMT4 underscores the critical need for research and awareness of these hereditary types of neuropathy.
• CMTX: Among the Charcot Marie Tooth types, CMTX stands out for its X-linked pattern of inheritance, contributing to the rich diversity of Charcot Marie Tooth disease types. This subtype affects both males and females differently, offering a unique perspective on the types of Charcot Marie Tooth disorder. CMTX is particularly notable for its impact on the peripheral nerves, leading to symptoms that can vary widely in severity. As researchers continue to explore how many types of Charcot-Marie-Tooth disease are there, CMTX remains a critical area of study for understanding this form of CMT.

The mutation is always hereditary, meaning it can be passed down from a parent to their child. The mutations originate in families by appearing spontaneously while DNA is forming in a child. Once there is a spontaneous mutation it can then be inherited by future children. CMT is something you are born with — it is not caused by anything you do and it is not contagious.

Symptoms of Charcot-Marie-Tooth Disease

The symptoms of Charcot-Marie-Tooth disease and the age when they begin depend on the type of CMT. Some people with CMT start experiencing symptoms as teens or young adults. Other types of CMT can cause symptoms in babies.

Less common symptoms of CMT can include sleep apnea, swallowing problems or choking, hearing loss, scoliosis, and breathing problems (from respiratory muscle weakness).

Testing for Charcot-Marie-Tooth Disease

Testing for Charcot-Marie-Tooth disease involves a comprehensive approach that integrates clinical evaluation, family history, and various diagnostic tests. This process is essential for diagnosing CMT and determining the specific subtype a patient may have.

Initially, a detailed medical history and neurological examination are conducted to assess symptoms consistent with peripheral nerve damage, a hallmark of CMT, and usually includes electrophysiological tests, such as nerve conduction studies and electromyography. These tests measure the electrical activity transmitted through the nerves and in the muscle and can help distinguish between the primary subtypes of CMT.

Given the genetic nature of CMT, genetic testing has become a key step in confirming the diagnosis. This test can detect the presence of gene mutations associated with the various forms of CMT. Genetic testing not only facilitates precise diagnosis, but also allows for more accurate treatment strategies and more understanding of the inheritance pattern. Having a genetic diagnosis also allows for more contribution to the advancement of drug development research.

In some cases, a nerve biopsy may be considered to further evaluate the structure and function of the peripheral nerves. This invasive procedure is less commonly performed today due to the advancements in genetic testing but can be useful in complex cases where the type of CMT remains unclear.

Together, these diagnostic approaches enable healthcare providers to identify the specific subtype affecting an individual to better manage the condition effectively and provide targeted interventions that address the unique challenges of the different types of Charcot Marie Tooth.

Treatments for Charcot-Marie-Tooth Disease

There are currently no known treatments or cures for Charcot-Marie-Tooth, but the following can help manage symptoms:

• Pain medication
• Braces or splints that support the feet and ankles
• Custom-made shoes or shoe inserts
• Physical therapy to help the muscles remain strong and flexible
• Occupational therapy to strengthen the muscles used for writing, gripping and other everyday tasks
• Surgery to correct joint deformities
• Hearing aids to help with hearing loss

While No Treatments or Cures Currently Exist for Charcot-Marie-Tooth Disease, the Science to Change That Does

Now that scientists know of more than 100 gene mutations that cause CMT, they can work to develop drugs that will target those genes or their functions. The CMT Research Foundation is solely focused on funding CMT research that has the promise to deliver safe and effective treatments for people with all forms of CMT. By pursuing creative and unconventional strategies to advance scientific discovery and partnering with researchers, medical experts, industry leaders and patients, we’re speeding urgently needed progress and answers to families once and for all.

Everything You Need to Know About Charcot-Marie-Tooth Disease in Five Minutes

Want to better understand CMT, the peripheral nervous system, CMT genetics and therapy development? Watch these three CMT 101 videos from research expert Dr. Grace Pavlath.