Charcot-Marie-Tooth disease type 1A (CMT1A) is the most frequently inherited peripheral neuropathy, a disorder affecting the nerves outside the brain and spinal cord. It is categorized as a demyelinating neuropathy, meaning it damages the protective myelin sheath. This chronic and progressive condition affects both motor nerves, which control muscle movement, and sensory nerves, which transmit signals for touch, pain, and temperature. The resulting nerve damage and physical symptoms gradually worsen over an individual’s lifetime.
The Genetic Basis of CMT1A
CMT1A is a hereditary condition caused by a specific alteration in the genetic code: a duplication of a segment of DNA on chromosome 17. This duplicated region includes the PMP22 gene, which codes for the Peripheral Myelin Protein 22. Individuals with CMT1A possess three copies of the gene instead of the standard two. This increased gene dosage causes Schwann cells, which produce myelin in the peripheral nervous system, to overproduce the PMP22 protein.
Myelin is an insulating sheath around nerve fibers that ensures rapid electrical signal transmission. The excess PMP22 protein disrupts the formation and maintenance of this sheath, a process called demyelination. This results in improperly formed, thinned, or absent myelin segments, significantly slowing and uncoordinating electrical signals traveling along the nerves. The disease follows an autosomal dominant inheritance pattern, meaning inheriting one copy of the duplicated gene is sufficient to develop the condition.
Clinical Manifestations and Progression
Symptoms typically begin in childhood or adolescence, though severity varies widely. The condition primarily affects the distal extremities, starting with the lower legs and feet, where muscles weaken and waste away symmetrically. This weakness often targets the muscles responsible for lifting the foot, causing foot drop. Foot drop results in a characteristic high-stepping or “steppage” gait, as individuals must lift their knees higher to clear their toes while walking.
Over time, the muscle imbalance in the feet leads to structural deformities. Common deformities include a high arch (pes cavus) and hammer toes, where the toes are permanently curled. These changes cause difficulties with balance and increase the risk of falls and ankle sprains. The slow progression of muscle atrophy gives the lower legs a distinct appearance, sometimes described as an inverted champagne bottle or stork leg.
As the disease progresses, often years after onset, weakness and atrophy extend to the hands and forearms. This severely impairs fine motor skills, making daily tasks like buttoning clothes or writing challenging. The lack of muscle support can also lead to hand deformities, such as the “claw hand” appearance. CMT1A also involves sensory nerve damage, causing a loss of sensation in the same distal areas. Individuals may experience numbness or reduced ability to feel pain, temperature, and light touch in the feet, extending up the legs and into the hands. Sensory nerve damage also affects proprioception, the body’s sense of limb position, further contributing to poor balance and coordination.
Diagnostic Procedures
Diagnosis begins with a thorough clinical examination and review of the patient’s history. The physician looks for physical signs, including reduced or absent deep tendon reflexes, characteristic foot deformities, and distal muscle wasting. A neurologist assesses muscle strength, gait, and sensory responses. The next step is electrodiagnostic testing, which includes Nerve Conduction Velocity (NCV) studies.
This test measures the speed and strength of electrical signals traveling through peripheral nerves. In CMT1A, demyelination causes a marked and uniform slowing of NCV. Motor NCV readings in the upper limbs are typically severely reduced, often falling below 38 meters per second, strongly suggesting a demyelinating neuropathy. Electromyography (EMG) is often performed alongside NCV to assess muscle electrical activity. The final and most definitive step is genetic testing, the gold standard for confirmation. Genetic testing analyzes a blood or saliva sample to identify the specific duplication of the PMP22 gene on chromosome 17, confirming CMT1A.
Current Management Strategies
Since no treatment can reverse the nerve damage, CMT1A management focuses on supportive care and maximizing function through a multidisciplinary approach. Physical therapy (PT) and occupational therapy (OT) are central to the plan. PT focuses on exercises to maintain muscle strength, flexibility, and range of motion, preventing contractures and joint stiffness. OT provides strategies and tools to help individuals adapt to fine motor skill difficulties, assisting with daily activities.
Stretching is encouraged to prevent muscle shortening, and low-impact aerobic exercises like swimming or cycling maintain fitness without excessive strain. Orthotic devices play a major role in managing physical effects. Ankle-Foot Orthoses (AFOs) are commonly prescribed to support the ankle and prevent foot drop, improving gait stability and reducing tripping hazards. Specialized shoes are often needed to accommodate structural foot deformities.
For severe deformities causing pain or impaired mobility despite orthotic use, surgical intervention may be considered. Common procedures include osteotomies (reshaping bones) and tendon transfers (rerouting working tendons). Pain management addresses chronic musculoskeletal pain resulting from abnormal mechanics. Regular monitoring by a neurologist and foot specialist tracks progression and adjusts the management plan.