10 Key Symptoms of Charcot-Marie-Tooth Disease You Should Know

Charcot-Marie-Tooth disease (CMT) is a group of inherited neurological disorders that affect the peripheral nerves, which control muscle movement and sensation in the limbs. Named after the three physicians who first described it in 1886, CMT disease is one of the most common inherited neurological conditions, affecting approximately 1 in 2,500 people worldwide. This progressive disorder primarily damages the nerves in the arms and legs, leading to muscle weakness, sensory loss, and various physical deformities.

Understanding the symptoms of Charcot-Marie-Tooth disease is crucial for early detection and proper management. While CMT is typically not life-threatening, it can significantly impact quality of life. The severity and progression of symptoms vary greatly among individuals, even within the same family. Some people experience mild symptoms that may go unnoticed for years, while others develop more severe complications that affect mobility and daily activities.

In this comprehensive guide, we’ll explore the ten most common symptoms of CMT disease, helping you recognize the warning signs and understand what to expect from this condition.

1. Progressive Muscle Weakness in the Lower Legs and Feet

One of the earliest and most characteristic symptoms of Charcot-Marie-Tooth disease is progressive muscle weakness in the lower legs and feet. This weakness typically begins in the muscles that control the feet and ankles, particularly affecting the peroneal muscles on the outer part of the lower leg.

As these muscles weaken, individuals may experience:

• Difficulty lifting the front part of the foot (foot drop)
• Tendency to trip or stumble frequently
• A high-stepping gait to compensate for foot drop
• Reduced ability to walk on heels
• Weakness when standing on tiptoes

This muscle weakness gradually worsens over time, though the rate of progression varies considerably among patients. In the early stages, individuals may notice they tire more easily during physical activities or have difficulty with tasks that require foot and ankle strength. As the condition advances, the weakness may extend upward into the thighs and eventually affect the hands and forearms, though lower limb involvement typically remains more severe.

2. Foot Deformities and High Arches

Foot deformities are hallmark physical signs of Charcot-Marie-Tooth disease, with high arches (pes cavus) being the most common abnormality. These structural changes occur due to the imbalance between weakened and stronger muscles, which pulls the foot into abnormal positions over time.

Common foot deformities associated with CMT include:

• High arches (pes cavus): An exaggerated arch that makes the foot appear unusually curved
• Hammer toes: Toes that bend downward at the middle joint, resembling a hammer
• Claw toes: Toes that curl under and grip downward
• Inverted heel: The heel turns inward, affecting stability

These deformities can make it challenging to find comfortable, properly fitting shoes and may cause pain when walking or standing for extended periods. The high arches concentrate weight on the heel and ball of the foot, leading to calluses, pressure sores, and discomfort. Many individuals with CMT require specialized footwear or custom orthotics to accommodate these structural changes and provide adequate support.

3. Loss of Muscle Mass in the Lower Legs

As Charcot-Marie-Tooth disease progresses, significant muscle atrophy (wasting) occurs in the lower legs, creating a distinctive appearance often described as “inverted champagne bottle” or “stork legs.” This muscle loss results from the denervation of muscle tissue—when damaged nerves can no longer properly stimulate the muscles.

The muscle atrophy in CMT typically follows this pattern:

• Begins in the muscles below the knee, particularly the anterior and lateral compartments
• Creates a noticeable contrast between thin lower legs and relatively normal-appearing thighs
• Progresses slowly over years or decades
• May eventually affect the hands and forearms, creating a similar wasting pattern in the upper extremities

While the visual appearance can be concerning, the muscle atrophy itself is generally painless. However, the weakness associated with muscle loss significantly impacts function and mobility. The degree of atrophy often correlates with the severity of weakness and functional impairment, though this relationship isn’t always linear.

4. Decreased Sensation and Numbness

Sensory symptoms are a significant component of Charcot-Marie-Tooth disease, as the condition affects both motor and sensory nerves. Many individuals with CMT experience reduced sensation in their extremities, particularly in the feet and hands, following a “stocking-glove” distribution pattern.

Sensory changes in CMT disease include:

• Numbness: Reduced or absent feeling in the feet and lower legs, sometimes extending to the hands
• Decreased temperature sensation: Difficulty distinguishing between hot and cold
• Reduced pain perception: Diminished ability to feel pain, increasing injury risk
• Loss of proprioception: Decreased awareness of foot and hand position in space
• Tingling or “pins and needles”: Abnormal sensations called paresthesias

The sensory loss in CMT can be problematic for several reasons. Reduced pain sensation may lead to unnoticed injuries, particularly on the feet, which can develop into serious wounds or infections. Decreased proprioception contributes to balance problems and increases fall risk. Some individuals may not realize the extent of their sensory loss until they experience an injury they didn’t feel or notice they can’t detect temperature differences when testing bathwater.

5. Difficulty with Fine Motor Skills and Hand Weakness

While Charcot-Marie-Tooth disease typically affects the legs first and most severely, hand involvement is common as the condition progresses. Hand and finger weakness, along with muscle atrophy in the intrinsic hand muscles, can significantly impact daily activities that require fine motor control.

Hand-related symptoms of CMT include:

• Difficulty buttoning shirts or handling small objects
• Weakness when gripping or grasping items
• Trouble with handwriting, which may become less legible over time
• Reduced manual dexterity when performing tasks like typing or using utensils
• Visible muscle wasting in the hands, particularly between the thumb and index finger
• Tremor in the hands, which occurs in some CMT variants

Hand weakness in CMT tends to develop later than leg symptoms and progresses more slowly. However, even mild hand involvement can be particularly frustrating as it affects numerous daily tasks that many people take for granted. Occupational therapy and adaptive devices can help individuals maintain independence despite these challenges.

6. Balance Problems and Frequent Falls

Balance difficulties are a common and potentially dangerous symptom of Charcot-Marie-Tooth disease, resulting from a combination of factors including muscle weakness, sensory loss, and foot deformities. Maintaining proper balance requires complex coordination between muscles, sensory feedback, and the vestibular system—all of which can be affected by CMT.

Balance impairment in CMT stems from:

• Ankle weakness: Inability to make quick adjustments to maintain stability
• Proprioceptive loss: Reduced awareness of foot position and ground contact
• Foot drop: Unexpected catching of the toes on uneven surfaces
• Foot deformities: Altered biomechanics affecting stability
• Muscle atrophy: Reduced strength for corrective movements

These balance problems increase the risk of falls, which can lead to injuries such as fractures, sprains, or head trauma. Many individuals with CMT report tripping over small obstacles, struggling on uneven terrain, or having difficulty in low-light conditions when visual cues can’t compensate for reduced proprioception. Using assistive devices like ankle-foot orthoses (AFOs), canes, or walkers can significantly improve stability and reduce fall risk.

7. Fatigue and Reduced Stamina

Chronic fatigue is an often underrecognized but significant symptom of Charcot-Marie-Tooth disease that can substantially impact quality of life. Unlike normal tiredness that improves with rest, CMT-related fatigue is persistent and disproportionate to activity level.

Several factors contribute to fatigue in CMT:

• Increased energy expenditure: Weakened muscles require more effort to perform normal activities
• Compensatory movements: Altered gait patterns and compensatory strategies consume extra energy
• Poor sleep quality: Discomfort, muscle cramps, or restless legs may disrupt sleep
• Muscle overuse: Remaining functional muscles work harder to compensate for weakened ones
• Psychological factors: The stress of managing a chronic condition contributes to mental and physical exhaustion

Individuals with CMT often describe needing more rest than peers, experiencing “crashes” after physical activity, or feeling exhausted by tasks that others find routine. This fatigue can affect work performance, social activities, and overall well-being. Energy conservation techniques, appropriate exercise programs, and strategic rest periods can help manage this challenging symptom.

8. Muscle Cramps and Pain

While Charcot-Marie-Tooth disease is primarily a motor and sensory neuropathy, many individuals experience muscle cramps and various types of pain. These symptoms can range from mild discomfort to severe pain that significantly affects quality of life.

Pain and cramping in CMT may include:

• Muscle cramps: Sudden, painful muscle contractions, often occurring in the calves, feet, or hands
• Neuropathic pain: Burning, shooting, or stabbing sensations caused by nerve damage
• Musculoskeletal pain: Aching in joints and muscles from altered biomechanics and overuse
• Foot pain: Discomfort from deformities, calluses, or abnormal pressure distribution
• Back and hip pain: Resulting from gait abnormalities and postural compensations

Nighttime leg cramps are particularly common in CMT and can disrupt sleep. The pain experienced in CMT can be chronic or intermittent, and its severity doesn’t always correlate with the degree of weakness or disability. Managing pain in CMT often requires a multifaceted approach, and individuals experiencing significant pain should consult with their healthcare provider about appropriate management strategies.

9. Foot Drop and Abnormal Gait

Foot drop—the inability to lift the front part of the foot—is one of the most functionally significant symptoms of Charcot-Marie-Tooth disease. This condition results from weakness in the muscles responsible for dorsiflexion (lifting the foot upward) and leads to characteristic gait abnormalities.

Foot drop in CMT causes several walking difficulties:

• Steppage gait: A high-stepping walk where the knee is lifted unusually high to prevent the toes from dragging
• Foot slap: The foot slaps down loudly when taking a step due to inability to control descent
• Toe dragging: The toes scrape along the ground, causing shoe wear and tripping hazards
• Reduced walking speed: Modified gait pattern slows overall walking pace
• Increased fall risk: Catching the toe on carpets, curbs, or uneven surfaces

The altered gait pattern requires significantly more energy than normal walking, contributing to fatigue and reduced walking distances. Many people with CMT benefit from ankle-foot orthoses (AFOs), which are braces that support the foot and ankle, helping to maintain proper foot position during walking and reducing the risk of trips and falls.

10. Decreased or Absent Reflexes

Diminished or absent deep tendon reflexes, particularly in the ankles, are common neurological findings in Charcot-Marie-Tooth disease and often among the earliest detectable signs during a clinical examination. Reflexes are typically tested by tapping tendons with a reflex hammer to elicit an automatic muscle contraction response.

Reflex abnormalities in CMT typically present as:

• Absent ankle reflexes (Achilles reflex): Usually the first and most consistently affected
• Reduced or absent knee reflexes (patellar reflex): Often affected as the disease progresses
• Decreased upper extremity reflexes: May occur in advanced cases or certain CMT subtypes
• Preserved reflexes initially: Early in the disease, reflexes may be normal or only slightly diminished

The loss of reflexes occurs because the damaged peripheral nerves cannot properly transmit the signals necessary for the reflex arc to function. While absent reflexes themselves don’t typically cause symptoms that patients notice, they are important diagnostic clues that help physicians identify and classify the type of peripheral neuropathy. During medical evaluations, reflex testing is a standard component of the neurological examination and can help track disease progression over time.

Main Causes of Charcot-Marie-Tooth Disease

Charcot-Marie-Tooth disease is a genetic disorder caused by mutations in genes that are responsible for the structure and function of peripheral nerves. Understanding the underlying causes helps explain why symptoms develop and how the disease is transmitted through families.

Genetic mutations: CMT is caused by mutations in more than 100 different genes, each affecting peripheral nerve function in different ways. These genetic defects impact either the myelin sheath (the protective coating around nerves) or the axon (the nerve fiber itself).

Types of CMT based on inheritance patterns:

• Autosomal dominant inheritance: The most common pattern, where a child has a 50% chance of inheriting the condition if one parent carries the mutation. CMT1A, caused by duplication of the PMP22 gene, accounts for approximately 70% of CMT cases.
• Autosomal recessive inheritance: Requires both parents to carry a copy of the mutated gene, with a 25% chance of an affected child. These forms are less common but often more severe.
• X-linked inheritance: Mutations on the X chromosome, typically affecting males more severely than females. CMTX1, caused by mutations in the GJB1 gene, is the second most common form of CMT.
• De novo mutations: In some cases, the genetic mutation occurs spontaneously without being inherited from either parent.

Mechanism of nerve damage: The genetic mutations in CMT lead to nerve damage through various mechanisms. In demyelinating forms (CMT1), the myelin sheath deteriorates, slowing nerve signal transmission. In axonal forms (CMT2), the nerve fiber itself is damaged, affecting signal strength. Both types result in progressive muscle weakness and sensory loss.

Classification of CMT: CMT is classified into several types based on the genetic mutation and whether it primarily affects myelin or axons. The main categories include CMT1 (demyelinating), CMT2 (axonal), CMT3 (severe demyelinating), CMT4 (autosomal recessive), and CMTX (X-linked). Each subtype may have slightly different symptom patterns and progression rates.

Frequently Asked Questions

Is Charcot-Marie-Tooth disease fatal?

CMT is generally not life-threatening, and most people with the condition have a normal or near-normal lifespan. However, the disease can significantly impact quality of life and mobility. In rare, severe cases, respiratory muscle involvement may occur, but this is uncommon.

At what age do CMT symptoms typically appear?

Symptoms most commonly begin in adolescence or early adulthood, though onset can range from early childhood to middle age. Some individuals may not notice symptoms until their 30s, 40s, or even later. The age of onset and severity can vary considerably, even among family members with the same genetic mutation.

Can Charcot-Marie-Tooth disease be cured?

Currently, there is no cure for CMT. Treatment focuses on managing symptoms, maintaining function, and preventing complications through physical therapy, occupational therapy, orthotic devices, and sometimes surgery for severe foot deformities. Research into gene therapy and other potential treatments is ongoing.

How is CMT disease diagnosed?

Diagnosis typically involves a combination of clinical examination, family history assessment, nerve conduction studies, electromyography (EMG), and genetic testing. Nerve conduction studies can identify abnormalities in nerve function, while genetic testing can confirm the specific mutation and CMT subtype.

Will I need a wheelchair if I have CMT?

Most people with CMT remain ambulatory (able to walk) throughout their lives, though many benefit from assistive devices such as ankle-foot orthoses, canes, or walkers. Only a small percentage of individuals with severe forms of CMT eventually require wheelchair use. The progression and severity vary greatly among individuals.

Can exercise help with CMT symptoms?

Yes, appropriate exercise can be beneficial for people with CMT. Low-impact activities like swimming, cycling, and gentle stretching can help maintain muscle strength, flexibility, and cardiovascular fitness without overworking weakened muscles. It’s important to work with a physical therapist familiar with CMT to develop a safe, effective exercise program.

Is CMT the same as muscular dystrophy or multiple sclerosis?

No, CMT is distinct from both muscular dystrophy and multiple sclerosis. CMT is a peripheral neuropathy affecting the nerves outside the brain and spinal cord. Muscular dystrophy primarily affects muscle tissue itself, while multiple sclerosis affects the central nervous system (brain and spinal cord). These are separate conditions with different causes and symptoms.

Can CMT affect other body systems besides nerves and muscles?

CMT primarily affects peripheral nerves and the muscles they control. However, some subtypes may occasionally involve other symptoms such as hearing loss, vocal cord paralysis, or breathing difficulties. These additional manifestations are relatively uncommon and depend on the specific genetic mutation.

Should I see a specialist for CMT?

Yes, individuals with CMT benefit from care by a neurologist, particularly one specializing in neuromuscular disorders. A multidisciplinary team may also include physical therapists, occupational therapists, orthotists, orthopedic surgeons, and genetic counselors. Regular monitoring helps manage symptoms and prevent complications.

If I have CMT, what are the chances my children will inherit it?

The inheritance risk depends on the type of CMT and inheritance pattern. For autosomal dominant CMT (the most common type), each child has a 50% chance of inheriting the condition. Genetic counseling can provide personalized information based on your specific genetic mutation and family history.

References:

• National Institute of Neurological Disorders and Stroke – Charcot-Marie-Tooth Disease
• Mayo Clinic – Charcot-Marie-Tooth Disease
• Johns Hopkins Medicine – Charcot-Marie-Tooth Disease
• Charcot-Marie-Tooth Association
• GeneReviews – Charcot-Marie-Tooth Hereditary Neuropathy Overview
• Muscular Dystrophy Association – Charcot-Marie-Tooth Disease