Hereditary Motor and Sensory Neuropathy

Hereditary motor and sensory neuropathy is a group of inherited conditions that progressively damage the nerves connecting your brain and spinal cord to the rest of your body, causing muscle weakness, sensory changes, and foot problems that can affect your daily life.

Charcot-Marie-Tooth disease, HMSN, peroneal muscular atrophy, hereditary sensory motor neuropathy

Table of contents

• What is hereditary motor and sensory neuropathy?
• Types of hereditary motor and sensory neuropathy
• What causes this condition?
• Signs and symptoms
• How is it diagnosed?
• Treatment options
• Living with the condition

What is hereditary motor and sensory neuropathy?

Hereditary motor and sensory neuropathy (HMSN) refers to a group of inherited conditions that affect the peripheral nervous system—the network of nerves outside your brain and spinal cord that control muscles and relay sensory information like touch from your limbs to your brain.^[1] These conditions are also commonly known as Charcot-Marie-Tooth disease, named after the physicians who first described the disorder in 1886.^[4]

This is the most commonly inherited peripheral nerve disorder, affecting about 2.4% of people globally, with rates increasing to between 5% and 7% among people aged 45 and older.^[1] The condition is characterized by progressive damage to the peripheral nerves, which means the nerves gradually become less able to function properly over time.^[1]

The peripheral nerves are responsible for transmitting signals between the brain, spinal cord, and the body’s muscles and sensory organs. When you have HMSN, these nerves become unresponsive over time and cause symptoms such as muscle weakness, decreased sensation, and abnormal reflexes.^[1] The severity and specific symptoms can be different for everyone, even within families where this condition is present.^[1]

Types of hereditary motor and sensory neuropathy

Hereditary motor and sensory neuropathy includes several different subtypes. The two most well-known conditions that fall under this category are Charcot-Marie-Tooth disease and peroneal muscular atrophy.^[1]

Charcot-Marie-Tooth disease (CMT) affects the peripheral nerves in the arms and legs, leading to muscle weakness, foot deformities, and sensory loss.^[1] This is the most common form of hereditary motor and sensory neuropathy.^[2]

Peroneal muscular atrophy specifically targets the muscles in the lower legs, resulting in weakness and wasting of muscles in these areas.^[1]

The conditions were historically classified into different groups based on how they affected the nerves. In 1968, doctors classified HMSN into seven main types.^[4] Type 1 (HMSN1) is characterized by slow nerve signals and affects the protective covering of nerves called myelin. Type 2 (HMSN2) mainly affects the nerve fibers themselves rather than their covering. Type 3 (HMSN3), also known as Dejerine-Sottas disease, begins in infancy and causes more severe symptoms than types 1 and 2.^[4]

Traditional classification was based on nerve conduction velocity—how fast electrical signals travel through your nerves—and the pattern of inheritance within families.^[6] As understanding of the genetic basis evolved, letters were added to represent specific genes involved.^[6]

What causes this condition?

All hereditary motor and sensory neuropathies are inherited, meaning they are passed down through families.^[4] The condition is caused by an inherited fault in one of the many genes responsible for the development of the peripheral nerves. This fault means the nerves become damaged over time.^[5]

HMSN is primarily caused by genetic mutations that affect the structure or function of proteins involved in the function and maintenance of the peripheral nervous system.^[1] Chromosomes 17 and 1 appear to be the most common chromosomes with mutations.^[4]

A child with hereditary motor and sensory neuropathy may have inherited the genetic fault responsible for the condition from one or both of their parents.^[5] The disease can be inherited in an autosomal dominant, autosomal recessive, or X-linked manner.^[4] There is no single faulty gene that causes the condition—there are many types caused by different genetic faults, and these can be inherited in several different ways.^[5]

The chances of passing the condition to your child depend on the specific genetic faults you and your partner carry.^[5]

Signs and symptoms

Hereditary motor and sensory neuropathy affects both sensory and motor functions. The symptoms can vary in severity and how they present themselves, but they generally include disturbances in sensation and movement.^[1]

Symptoms of the condition usually start to appear between the ages of 5 and 15, although they sometimes do not develop until well into middle age or later.^[5] They most often begin in the feet and legs, but in time, they may affect the hands and arms.^[3] Neuropathy disorders usually have onset in childhood or young adulthood, and motor symptoms seem to be more predominant than sensory symptoms.^[4]

Sensory symptoms

Sensory symptoms often involve changes to feeling and perception. If you have HMSN, you may experience numbness, tingling sensations, and a reduced ability to feel pain or temperature changes.^[1] These sensory symptoms can affect various parts of the body, including the hands, feet, and limbs.^[1] Loss of sensation in the legs and feet is common, and while usually described as “painless,” the neuropathy can be painful.^[1]

Motor symptoms

Motor symptoms typically present as weakness, muscle wasting, and difficulties with coordination and balance.^[1] Affected individuals may have trouble walking, running, or performing tasks that require fine motor skills. Muscle weakness can progress over time and may lead to significant impairments in mobility.^[1]

Common motor symptoms include weakness in the legs, ankles, and feet; muscle shrinking in the legs and feet that can cause the calves to look like an upside-down champagne bottle; not being able to run; trouble lifting the foot at the ankle, called footdrop; clumsy walking; and tripping or falling often.^[3]

Other physical features

People with hereditary motor and sensory neuropathy may have highly arched or very flat feet, curled toes called hammertoes, and an awkward way of walking.^[5] Some may also develop foot deformities, thin calf muscles, or scoliosis, which is curvature of the spine.^[4] Reduced reflexes and loss of balance are also common.^[4]

It is important to understand that symptoms may present themselves very differently in each person. While certain symptoms may be common, such as sensory abnormalities and muscle weakness, the severity and specific manifestations can vary widely.^[1] How bad the symptoms are varies greatly from person to person, even among family members.^[3]

How is it diagnosed?

Diagnosing hereditary motor and sensory neuropathy involves a combination of a physical exam, review of your medical history and symptoms, and specialized tests.^[1]

If you think you may have symptoms of the condition, you should see your doctor. If they suspect hereditary motor and sensory neuropathy, they will refer you to a doctor who specializes in treating conditions of the nervous system, called a neurologist, for further tests to confirm the diagnosis.^[5]

Medical history and physical examination

Your healthcare provider will begin by taking a detailed medical history, including symptoms experienced and any family history of neurological and genetic disorders.^[1] During your physical exam, your provider will perform a neurological exam to assess muscle strength, sensation, reflexes, and coordination.^[1] The characteristic distribution of motor weakness, foot deformities, and family history suggests hereditary neuropathy.^[8]

Nerve function tests

Your provider may recommend nerve function tests to identify the type, location, and extent of any nerve damage.^[1] Nerve conduction studies (NCS) are commonly used to assess the function of peripheral nerves by measuring how fast electrical signals travel through them.^[1] Electromyography (EMG) measures muscle reaction and can help clinicians decide what type of motor and sensory neuropathy it is and how severe the disease is.^[4]

Imaging tests

Imaging tests may be used to rule out other conditions. CT scans of the spine can show herniated discs, narrowing of the spinal canal, tumors, and bone irregularities that may affect nerves. MRI scans of the spine can reveal tumors or nerve root compression, also known as a pinched nerve.^[1]

Genetic testing

Genetic testing can confirm the presence of specific gene mutations associated with hereditary motor and sensory neuropathy.^[1] Final confirmation can come through genetic testing, which is available for many types of the condition.^[4]

Other tests

In rare cases, a nerve biopsy may be recommended to examine a small sample of nerve tissue under a microscope.^[1] This can detect specific changes in the nerves that help confirm the diagnosis.^[4]

Treatment options

There is currently no cure for hereditary motor and sensory neuropathy.^[5] However, treatments can help relieve symptoms, aid mobility, and increase independence and quality of life for people with the condition.^[5] Treatment is mainly symptomatic and supportive, aimed at helping you maintain your independence and mobility.^[8]

Physical therapy

Physical therapy is vital for people living with hereditary motor and sensory neuropathy.^[1] The goal of physical therapy is to help you maintain your independence and mobility by providing strengthening exercises and flexibility training. Stretching and assistive devices also help to keep you mobile.^[1]

Occupational therapy

Occupational therapy can help you adapt to daily tasks and maintain independence as symptoms progress.^[5]

Bracing and assistive devices

Bracing may be used to improve mobility and provide support.^[5] Casting and bracing are necessary to stabilize the affected foot and ankle and provide structure to keep the bones from deforming. They also help with gait issues and footdrop due to nerve damage.^[1] Walking aids may also be helpful.^[5]

Pain management

Nerve damage from hereditary motor and sensory neuropathy often leads to chronic pain in the legs and feet. If needed, pain medication may be prescribed to manage discomfort not relieved by over-the-counter medications.^[1]

Surgery

In some cases, surgery may be needed to correct problems such as flat feet and muscle contractures, where muscles shorten and lose their normal range of movement.^[5] If nonsurgical treatments have not stopped the damage, surgery may be necessary to realign the bones in the foot to assist with shoe wear problems and mobility.^[1] Orthopedic surgery may be needed to correct severe foot or other skeletal deformities.^[8]

Living with the condition

Hereditary motor and sensory neuropathy is a progressive condition, meaning the symptoms slowly get worse over time, making everyday tasks increasingly difficult.^[5] The condition is not life-threatening, and most people with it have the same life expectancy as a person without the condition.^[5] However, it can make everyday activities very difficult.^[5]

The prognosis for individuals with hereditary neuropathies depends upon the type of neuropathy. Some types have very mild symptoms and may go undiagnosed for many years. Other types are more severe and are associated with more disabilities.^[8] Many patients struggle with nighttime symptoms that can cause insomnia and impact daytime activities because of disrupted sleep.^[1]

Living with a long-term progressive condition can also have a significant emotional impact. Some people find it helpful to speak to others with the condition through support groups. You may also benefit from a talking therapy, such as cognitive behavioral therapy (CBT).^[5]

If you or your partner have a family history of hereditary motor and sensory neuropathy and are considering having a baby, you should see your doctor. Your doctor can refer you for genetic counseling, where you can discuss your concerns and the options available with a genetics specialist.^[5] Genetic counseling is important to understand further details about the disease and prognosis.^[8]