Hereditary motor and sensory neuropathy is a group of inherited conditions that progressively damage the nerves responsible for muscle movement and sensation, most often beginning in the feet and legs during childhood or early adulthood.

Understanding Hereditary Motor and Sensory Neuropathy

Hereditary motor and sensory neuropathy, also commonly known as Charcot-Marie-Tooth disease or HMSN, represents a collection of genetic disorders that affect the peripheral nervous system—the network of nerves outside the brain and spinal cord. These nerves carry signals between the brain, spinal cord, muscles, and sensory organs, allowing us to move and feel. When someone has HMSN, genetic mutations interfere with the structure or function of proteins needed to maintain healthy peripheral nerves, causing them to gradually lose their ability to work properly over time.^[1]

The condition gets its name from three physicians who first described it in 1886: Jean-Martin Charcot, Pierre Marie, and Howard Henry Tooth. Unlike peripheral neuropathy caused by diabetes or other acquired conditions, HMSN is inherited, meaning it passes from parents to children through their genes.^[2]

This group of disorders includes several subtypes, with Charcot-Marie-Tooth disease being the most common, as well as peroneal muscular atrophy, which specifically targets muscles in the lower legs. While these conditions share common genetic causes, they may affect different body parts or progress at different rates.^[1]

How Common Is This Condition?

Hereditary motor and sensory neuropathy is considered the most commonly inherited peripheral polyneuropathy. Although specific global prevalence data for HMSN varies, these conditions affect a significant number of families worldwide.^[2]

The condition does not discriminate based on age, sex, race, or ethnicity—anyone can be affected if they inherit the genetic mutation. However, because HMSN is inherited, it tends to run in families, and multiple family members across generations may experience symptoms. Interestingly, even within the same family, the severity of symptoms can vary dramatically. Some family members may have only mild symptoms that barely affect their daily lives, while others may experience significant disability.^[3]

What Causes Hereditary Motor and Sensory Neuropathy?

All forms of hereditary motor and sensory neuropathy are caused by inherited genetic mutations. These mutations occur in genes that are responsible for the development and maintenance of peripheral nerves. When these genes don’t function properly, the nerves gradually deteriorate over time.^[4]

The condition can be inherited in several different patterns. In autosomal dominant inheritance, a child needs to inherit only one faulty gene from one parent to develop the condition. In autosomal recessive inheritance, a child must inherit faulty genes from both parents. There are also X-linked forms, where the genetic mutation is carried on the X chromosome. The specific pattern of inheritance affects how likely a child is to develop the condition based on their parents’ genetic makeup.^[4]

Research has identified that chromosomes 17 and 1 are among the most commonly affected by these mutations. There is no single faulty gene that causes HMSN—many different genetic faults have been identified, and different types of HMSN are associated with specific gene mutations. For example, one common subtype results from a duplication or deletion of the peripheral myelin protein-22 gene (PMP22) located on chromosome 17, accounting for 70 to 80% of certain HMSN cases.^[4][8]

Because hereditary motor and sensory neuropathy is genetic, it cannot be “caught” like an infection or developed later in life from lifestyle factors. If you have HMSN, you were born with the genetic mutation, even if symptoms don’t appear until later.

Risk Factors and Family History

The primary risk factor for hereditary motor and sensory neuropathy is having a family history of the condition. If one or both parents carry a genetic mutation associated with HMSN, their children may be at risk of inheriting the condition. The likelihood depends on the specific type of genetic mutation and the pattern of inheritance.^[5]

However, it’s important to understand that even if a parent has HMSN, not every child will necessarily develop symptoms. In some families with autosomal dominant inheritance, for example, each child has a 50% chance of inheriting the faulty gene. In autosomal recessive patterns, both parents must carry a copy of the faulty gene, and even then, each child has only a 25% chance of developing the condition.^[5]

Recognizing the Symptoms

The symptoms of hereditary motor and sensory neuropathy typically appear gradually and affect both movement (motor function) and sensation (sensory function). Most people first notice symptoms between ages 5 and 15, though some individuals don’t develop symptoms until middle age or later. In rare cases, symptoms may appear as early as infancy.^[5][6]

Motor Symptoms

Motor symptoms are often the most noticeable and typically appear first. These symptoms involve weakness and wasting of muscles, particularly in the lower legs and feet. People with HMSN may have trouble walking, running, or performing tasks that require fine motor skills. The muscle weakness in the calves can become so pronounced that the legs take on a distinctive appearance, sometimes described as resembling an upside-down champagne bottle.^[3]

Common motor symptoms include difficulty lifting the foot at the ankle (called footdrop), which leads to a clumsy walking pattern with frequent tripping or falling. Many people develop high-arched feet or curled toes called hammertoes. As the condition progresses, the weakness may spread from the feet and legs to the hands and arms, making it difficult to button clothes, write, or hold objects.^[3][7]

Sensory Symptoms

Sensory symptoms involve changes in how the body perceives touch, temperature, pain, and position. People with HMSN often experience numbness, tingling sensations, or reduced ability to feel pain or temperature changes. These sensory changes typically follow a pattern, starting in the feet and gradually moving upward in what doctors call a “stocking-glove pattern.”^[1][7]

The loss of sensation can be particularly dangerous because it means injuries or infections may go unnoticed. Someone with severe sensory loss might step on something sharp without realizing it, or develop a blister that becomes infected because they didn’t feel the initial discomfort.

Additional Symptoms

Beyond motor and sensory changes, people with HMSN may experience depressed or absent tendon reflexes—the automatic responses doctors test by tapping on tendons with a small hammer. Some individuals develop foot deformities that make finding comfortable shoes difficult. Balance and coordination problems are common as the condition affects the nerves that help the body maintain stability.^[4]

Although HMSN is often described as painless, many people do experience pain, which can range from mild discomfort to severe chronic pain that significantly impacts quality of life. In some cases, people with HMSN may develop scoliosis (curvature of the spine). Some subtypes can also cause sensorineural hearing loss.^[4][6]

It’s important to remember that symptom severity varies greatly from person to person, even among family members with the same genetic mutation. While certain symptoms are common, the specific manifestations and their impact on daily life can differ widely.^[1]

How Is HMSN Diagnosed?

Diagnosing hereditary motor and sensory neuropathy involves several steps and usually requires consultation with a specialist called a neurologist, who focuses on nervous system disorders. The diagnosis combines physical examination, family history review, specialized tests, and sometimes genetic analysis.^[1][5]

The process typically begins with a detailed medical history. Your healthcare provider will ask about symptoms you’re experiencing and whether anyone in your family has been diagnosed with neuropathy or has similar symptoms. A family history of foot deformities, walking difficulties, or muscle weakness can provide important clues.^[1]

During the physical examination, the doctor performs a neurological assessment to evaluate muscle strength, sensation, reflexes, and coordination. They’ll look for characteristic signs such as high-arched feet, muscle wasting in the legs, or depressed reflexes. These physical findings, combined with family history, often suggest the diagnosis.^[7]

Specialized Testing

Nerve conduction studies are among the most important diagnostic tools for HMSN. These tests measure how quickly electrical signals travel through nerves. In people with certain types of HMSN, nerve signals travel more slowly than normal. During the test, small electrical impulses stimulate the nerves, and sensors measure the response. While the test can be uncomfortable, it provides crucial information about nerve function.^[1]

Electromyography (EMG) often accompanies nerve conduction studies. This test measures the electrical activity of muscles and helps determine whether weakness stems from nerve damage or muscle problems. Together, these electrodiagnostic tests help doctors determine the type and severity of neuropathy.^[4]

Imaging tests like CT scans or MRI of the spine may be used to rule out other conditions that could be causing similar symptoms, such as herniated discs, spinal stenosis, or tumors affecting the nerves. These tests help ensure that symptoms aren’t due to compression or other structural problems.^[1]

In some cases, a nerve biopsy may be recommended. This involves removing a small sample of nerve tissue for examination under a microscope. The biopsy can reveal characteristic changes in nerve structure that help confirm the diagnosis and identify the specific type of HMSN.^[1]

Genetic Testing

Genetic testing can confirm the diagnosis by identifying specific gene mutations associated with HMSN. This testing typically involves a blood sample or tissue sample. Finding the specific genetic mutation not only confirms the diagnosis but also helps predict how the condition might progress and provides important information for family planning.^[7][11]

Final confirmation of HMSN often comes through a combination of these tests rather than any single test result. The diagnostic process can take time, but accurate diagnosis is essential for appropriate management and genetic counseling.

Can Hereditary Motor and Sensory Neuropathy Be Prevented?

Because hereditary motor and sensory neuropathy is caused by inherited genetic mutations, there is currently no way to prevent the condition from developing in someone who carries the faulty gene. If you were born with the genetic mutation, the condition will eventually manifest, though the timing and severity of symptoms can vary.^[5]

However, understanding your family history and seeking genetic counseling can help prospective parents make informed decisions. Genetic counseling provides information about inheritance patterns, the likelihood of passing the condition to children, and available reproductive options. This knowledge doesn’t prevent HMSN, but it helps families prepare and make choices based on complete information.^[5]

While the condition itself cannot be prevented, early diagnosis and intervention can help minimize complications and maintain quality of life. People with a family history of HMSN should be alert to early signs and seek medical evaluation if symptoms appear. Early treatment and supportive care can help preserve mobility and independence for as long as possible.

How HMSN Affects the Body

To understand how hereditary motor and sensory neuropathy affects the body, it helps to know how peripheral nerves normally work. Peripheral nerves are like electrical cables that transmit signals between the brain, spinal cord, and the rest of the body. These nerves have several components, including a central fiber called an axon that carries signals, and a protective coating called myelin that insulates the nerve and helps signals travel quickly.^[1]

In HMSN, genetic mutations disrupt the normal structure and function of these nerve components. There are two main patterns of nerve damage in HMSN. In demyelinating neuropathy, the myelin coating deteriorates, causing signals to travel more slowly through the nerves. This is like removing insulation from an electrical wire—the signal still travels, but much less efficiently. In axonal neuropathy, the nerve fibers themselves break down, which is more like cutting the wire entirely.^[4]

These changes in nerve structure lead to the symptoms people experience. When motor nerves are damaged, muscles don’t receive proper signals from the brain, resulting in weakness and eventually muscle wasting from disuse. When sensory nerves are damaged, information about touch, pain, temperature, and position doesn’t reach the brain properly, causing numbness, tingling, or loss of sensation.^[1]

The damage typically begins in the longest nerves first—those reaching the feet and lower legs—because these nerves are most vulnerable. This explains why symptoms usually start in the feet and gradually progress upward. As the condition advances over years, shorter nerves in the hands and arms may also become affected.^[6]

In some types of HMSN, repeated cycles of demyelination and remyelination (where the body tries to repair the myelin coating) occur. This process can cause peripheral nerves to become thickened and enlarged, sometimes to the point where they can be felt under the skin. Under the microscope, this creates a characteristic appearance called “onion bulbs.”^[8]

The progressive nature of nerve damage in HMSN means that symptoms gradually worsen over time. However, the rate of progression varies considerably among individuals. Some people experience very slow progression over decades, while others may have more rapid deterioration of nerve function.