Charcot-Marie-Tooth disease (CMT) is named after the three doctors who first described the disease in 1886: Jean-Martin Charcot (shar-coh), Pierre Marie, and Howard Henry Tooth. Today, CMT refers to any peripheral neuropathy with a genetic cause, whether or not the specific genetic mutation is known.
CMT is a rare multisystem, multiorgan disease that causes lifelong, progressive symptoms, including muscle weakness and atrophy in the arms and legs, sensory loss, and other complications. These symptoms often lead to challenges with balance, walking, hand use, and other daily activities.
How Does CMT Affect the Body?
CMT is a peripheral neuropathy affecting the nerves that connect the brain and spinal cord to the rest of the body. Peripheral nerves are responsible for movement, sensation, hearing, organ function, and more. For example, they allow you to sense touch, feel heat, or move your muscles based on signals from the brain.
CMT is also a neuromuscular disease. “Neuro” refers to nerves, and “muscular” refers to CMT’s impact on skeletal muscle, such as weakness and atrophy. With this in mind, CMT leads to muscle weakness, atrophy, and sensory loss, especially in the arms, hands, legs, and feet. In some cases, it can even affect autonomic nerves.
Because CMT encompasses a wide range of symptoms and causes, it is categorized into multiple classifications based on the underlying genetic cause and nerve impact. These classifications are referred to as the types.
Types of CMT
CMT is not a single disease but a group of peripheral neuropathies caused by mutations in more than 130 genes. CMTA has cataloged over 160 CMT subtypes, which are classified into broader categories, including:
- CMT1: Nerve conduction studies show a demyelinating neuropathy.
- CMT2: Nerve conduction studies show an axonal neuropathy.
- CMTX: The gene with the CMT-causing mutation is on the X chromosome.
- CMT4: Autosomal recessive demyelinating CMT.
- Intermediate CMT: Nerve conduction studies show a mix of demyelinating and axonal neuropathy.
Additional classifications include dHMN (distal hereditary motor neuropathy, also called hereditary motor neuropathy or HMN), dSMA (distal spinal muscular atrophy), GAN (giant axonal neuropathy), HMSN (hereditary motor and sensory neuropathy), HSAN (hereditary sensory and autonomic neuropathy), HSN (hereditary sensory neuropathy), and a category for “unclassified” subtypes known by their gene names, such as CMT-SORD and CMT-BAG3.
Although each subtype is rare, CMT affects more than 3 million people worldwide. CMTA-accelerated advances in genetic research have enabled better identification and understanding of CMT’s subtypes.
Symptoms, Diagnosis, and Inheritance
Understanding CMT’s symptoms, diagnostic process, and inheritance patterns provides a solid foundation for navigating CMT’s challenges.
Symptoms
CMT symptoms vary widely among individuals but commonly include muscle weakness, difficulty walking, balance problems, numbness, and chronic pain. Additional symptoms may include spinal deformities, fatigue, hearing loss, and, in some cases, breathing difficulties.
Diagnosis
Diagnosing CMT can be complex due to its overlap with other diseases. The process typically includes a thorough clinical evaluation, nerve conduction studies, and, in some cases, genetic testing to confirm the specific subtype.
Inheritance
CMT is an inheritable disease following specific inheritance patterns, such as autosomal dominant, autosomal recessive, and X-linked inheritance. Sometimes, CMT results from a de novo (new) mutation rather than being inherited.
What is CMTA Doing to Find a Cure?
CMTA is the global leader in driving research for treatments and a cure for CMT through the CMTA Strategy To Accelerate Research (STAR) program. Since 2008, CMTA-STAR has invested nearly $30 million in groundbreaking work.
Through CMTA-STAR’s collaborative research model, CMTA connects people living with CMT to clinicians, researchers, and industry experts to advance treatment development and improve quality of life. These cooperative efforts have propelled CMT research to the forefront of scientific innovation, enabling promising advancements in genetic therapy, drug development, and other potential treatments.
Next Steps: Find Your CMTA Center of Excellence
Understanding CMT is the first step in managing its challenges. CMTA Centers of Excellence provide comprehensive care for individuals and families, offering expert guidance and tailored treatment plans. Visit the CMTA Center of Excellence directory to find a location near you and take the next step in your CMT journey.
Become a Partner in CMT Research
Your participation is vital to accelerating research to bring treatments and a cure. We invite you to become a patient partner by registering today with CMTA’s Patients as Partners in Research. Registering today ensures you stay informed about the latest developments in CMT research. You’ll also be the first to know about any clinical trial or study you wish to participate in. Registration is free, secure, and open to everyone with CMT, no matter where you are in your journey.
