What is Charcot-Marie-Tooth (CMT) Disease?

Charcot-Marie-Tooth (CMT) disease is a hereditary neurological disorder that affects the peripheral nerves, responsible for transmitting signals between the brain, spinal cord, and muscles. CMT, also known as hereditary motor and sensory neuropathy, is one of the most common inherited neurological disorders, affecting an estimated 126,000 individuals in the United States and 2.6 million people worldwide [1]. CMT compromises patient lifestyles, everyday activities, and career and family choices. [2]. The disease is progressive, leading to muscle weakness and atrophy, particularly in the feet, legs, hands, and arms, and can significantly impact a person’s quality of life.

Types of Charcot-Marie-Tooth Disease

CMT is classified into several types based on the genetic mutations involved and the specific nerves affected:

1. CMT1: The most common form, CMT1, is caused by mutations in genes affecting the myelin sheath, the protective covering of nerve fibers [3]. This type leads to muscle weakness and sensory loss, especially in the legs and feet. CMT1 accounts for about 70-80% of all CMT cases [4].

2. CMT2: CMT2 involves damage to the nerve axons rather than the myelin sheath [5]. This type typically presents later in life and can cause significant muscle weakness and atrophy.

3. CMTX: Linked to the X chromosome, CMTX can affect both males and females, though males often experience more severe symptoms. It can cause symptoms similar to both CMT1 and CMT2 [6].

Causes of Charcot-Marie-Tooth Disease

CMT is caused by genetic mutations that affect the structure and function of peripheral nerves. The disease is primarily inherited in an autosomal dominant manner, meaning only one copy of the mutated gene from one parent is required to develop the disease [3]. About 90% of people with CMT inherit it from a parent with the condition, while the remaining cases are due to spontaneous mutations [7].

Symptoms of Charcot-Marie-Tooth Disease

Symptoms of CMT vary depending on the type and severity but generally include:

• Muscle weakness, especially in the lower legs and feet [9]
• Toe-walking and frequent tripping
• Difficulty walking, running, or maintaining balance [10]
• Frequent ankle rolls or sprains
• High foot arches or flat feet [11]
• Frequent kneecap dislocations
• Foot drop (difficulty lifting the front part of the foot) [12]
• Numbness or tingling in the hands and feet [13]
• Muscle cramps and decreased muscle mass [14]
• Difficulty with using writing or eating utensils, zippers, buttons, keys (problems with tasks involving fine motor skills)
• Fatigue
• Chronic pain in areas affected (pain can be neuropathic or musculoskeletal)

Statistics on Charcot-Marie-Tooth Disease

• Prevalence: CMT is one of the most common inherited neurological disorders, affecting an estimated 126,000 individuals in the United States and 2.6 million people worldwide [1]. Charcot-Marie-Tooth disease (CMT) affects 1 in 2,500 people and is caused by mutations in more than 30 genes [15].
• Types of CMT: The most common form, CMT1, accounts for 70-80% of all cases. CMT2 and CMTX are less common but still significantly impact those affected [4].
• Inheritance: About 90% of individuals with CMT inherit it from a parent, with the remaining 10% resulting from spontaneous genetic mutations [7]. Though there are a myriad of gene associations and mechanisms, four genes comprise over 90% of genetically confirmed cases of CMT [8].