Charcot-Marie-Tooth Disease
Overview
Charcot-Marie-Tooth (CMT) disease, also known as hereditary motor and sensory neuropathy (HMSN), is an inherited, degenerative nerve disorder that causes muscle weakness and atrophy in the feet, legs, hands, and forearms.It is characterized by progressive loss of use and sensation in the limbs.
Charcot, Marie, and Tooth are the names of the physicians who identified the disease and described its symptoms. It is not the same as Charcot foot disease, a neuropathic joint disease that is a common complication of diabetes mellitus.
In CMT, the myelin coating on motor and sensory nerves gradually deteriorates, resulting in poor transmission of nerve impulses. The feet and legs are the first to show the affects of myelin deterioration, or demyelination. Muscles fail to receive stimulation from the nerves and then begin to waste away (atrophy). Atrophy in the small muscles in the feet and hands causes the fingers and toes to curl.
Anatomy
Peripheral nerves extend from the spinal cord throughout the body. Nerve cells, or neurons, carry impulses to and from the brain via the spinal cord. Motor neurons signal muscles to move; sensory neurons transmit sensations, such as heat, pain, and surface texture to the brain.
Most neurons are made up of:
- a soma
- dendrites
- an axon, and
- synaptic terminals.
The soma contains a large nucleus and other structures responsible for proper maintenance and function of the neuron.
Dendrites are branching structures that extend from the soma. Dendrites may have hundreds or thousands of synapses that receive signals from other neurons and relay information to the soma.
The axon is an elongated structure that conducts signals from the soma to synaptic terminals. Each neuron has one axon, which is wrapped in multiple layers of a substance called myelin. Axons transmit signals at a constant speed, called nerve conduction velocity (NCV), which is determined by the diameter of the axon and by the thickness of its myelin sheath. Myelin is critical in nerve signal conduction.
Synaptic terminals are formed within the end of an axon. They contain chemicals (neurotransmitters) that relay signals from one neuron to other neurons or to tissues (i.e., muscles, glands).
Types
There are two forms of CMT. One form involves degeneration of the myelin sheath that surrounds a nerve's axon. The other involves impairment of the axon. There are several types of CMT within each form. The most commonly diagnosed type is CMT1. In patients with CMT1, there is axonal demyelination resulting in reduced motor and sensory nerve conduction. Loss of stimulation by the affected nerves causes muscle weakness and atrophy.
Incidence and Prevalence
Approximately 125,000 people in the United States have Charcot-Marie-Tooth disease. CMT occurs slightly more often in men than in women and is not prevalent in any one race. Signs of the disease usually appear before the age of 30.
Cause
CMT is caused by an inherited genetic mutation. There are rare cases in which the mutation occurs spontaneously within one egg or sperm.
Signs and Symptoms
Symptoms vary from mild to severe, from patient to patient, and even among family members with the disease. Symptoms are more severe in cases of early age of onset.
The first indications of CMT are mild, usually foot and ankle weakness, and fatigue. If the toes have started to curl into "claw toes," wearing shoes may become painful. Weakness in the hands also may be present.
Another sign of CMT is a highly arched foot (cavus arch). When the muscles of the foot weaken, an imbalance develops that typically raises the arch of the foot. This increases tension in the muscles on the bottom of the foot and worsens the curling of the toes.
A change in gait is another common sign. When atrophy progresses, the muscle in the front of the leg usually is the first affected. This produces two distinct characteristics in gait:
1. Swaying from side to side
2. Foot slapping the ground
Because the muscle in the front of the leg is deteriorating, it lacks the strength to pull the foot forward for the next step and the foot drags across the ground. People with CMT sway as they walk so the trailing foot can clear the ground.
The same muscle helps slowly lower the forefoot once the heel touches the ground. Because the muscle is weakened, the forefoot drops and slaps against the ground as soon as the heel touches down.
In later stages of the disease, most of the muscles below the knee have atrophied, producing thin, spindly calves and lower legs. Fractures and sprains of the ankle and lower leg are common. In rare severe cases, crutches or a wheelchair may be needed. Muscles above the knee usually are not affected.
An affected hand may turn in on itself, making ordinary activities like writing, fastening buttons, and opening doors and jars very difficult.
CMT disease also may produce these symptoms:
- Burning, tingling, numbness in hands and feet
- Chronic weakness and fatigue
- Difficulty with balance
- Difficulty with motor coordination (e.g., writing)
- Loss of sensation in hands and feet
- Lower leg and forearm muscle cramping
- Partial sight or hearing loss (rare)
- Scoliosis (rare)
- Weakened reflexes
Diagnosis
A physical examination may confirm a high arch, claw toes, and muscle weakness. The Achilles (above the heel) and patellar (knee) tendon reflexes are weak or absent. Muscle strength testing can reveal atrophy and can be used to establish a baseline from which disease progression can be tracked.
Examining and testing several family members for signs of neuropathy can help establish a diagnosis.
Tests
Several tests are used to determine reduced muscle responses and nerve damage.
- A nerve conduction velocity (NCV) study measures the speed of nerve signal conduction. A patient with CMT1 has slower than normal NCV readings due to myelin deterioration.
- Electromyography (EMG) records muscle activity during voluntary contractions and when electrically stimulated. It also determines if muscles are receiving neurological stimulation.
- Magnetic resonance imaging (MRI scan) establishes whether the nerves in the spinal cord have been affected (rare).
- A DNA blood test can identify some types of the disorder.
EMG and NCV tests, which can be used in combination, are often referred to as EMG/NCV studies.
Treatment
Treatment for CMT depends on the severity of symptoms and the age of the patient. The goal is to make the patient comfortable and increase the ability to perform daily activities.
Orthotics
Orthotics may be prescribed to improve mobility and gait, provide support, and decrease risk of injury.
In the early stages of CMT, foot deformities can be corrected with braces that help maintain proper foot and leg alignment and reduce the risk of sprains. Splints are used on the forearm and hand.
If muscle weakness in the leg causes the foot to drag while walking, the patient can be fitted with a special brace that holds the foot at a 90-degree angle to the leg. If the entire lower leg is severely weakened, braces that extend above the knee and attach to the stronger muscles of the upper leg can provide adequate support.
Custom-made shoes and/or inserts can improve gait and redistribute the weight of the body on the foot.
Physical therapy
Physical therapy helps maintain muscle strength and endurance in the affected limbs.
Surgery
If rigid foot deformity prevents the foot from being manipulated into proper alignment with a brace, surgery may help. The goal of surgery is to help the foot and leg function as normally as possible, so the patient can walk with minimal difficulty. When foot muscles are too weak to hold the bones in proper position, the foot bones can be surgically fused to provide stability and support.
Prognosis
Foot and hand deformity and walking problems are lifelong disabilities. Mental function and longevity usually are not affected, however, and most people with CMT lead productive lives.