In a recent with the Today show's Jenna Bush Hager, iconic country singer Alan Jackson revealed that he has been suffering from an increasingly debilitating nerve disorder. Jackson, 62, said he had been diagnosed with Charcot-Marie-Tooth (CMT) disease 10 years ago, but that the symptoms have recently started to become more noticeable.
"I have this neuropathy and neurological disease. It's genetic that I inherited from my daddy," Jackson said. "There's no cure for it, but it's been affecting me for years. And it's getting more and more obvious. And I know I'm stumbling around on stage. And now I'm having a little trouble balancing, even in front of the microphone, and so I just feel very uncomfortable."
Jackson went on to say, "It's not going to kill me. It's not deadly." And he noted that he doesn't have any plans to retire yet: "I'm not saying I won't be able to tour. I'll try to do as much as I can."
What is CMT?
Charcot-Marie-Tooth disease, named for the three physicians who described it in 1886, is one of a group of disorders that cause damage to the peripheral nerves as well as sensory information back to the spinal cord and brain. CMT can also directly affect the nerves that control the muscles. Progressive muscle weakness typically becomes noticeable in adolescence or early adulthood, but the onset of the disease can occur at any age.
According to the National Institute of Neurological Disorders and Stroke, , affecting an estimated 150,000 individuals in the United States and 2.6 million worldwide.
There are over 40 types of CMT. It is even possible to have two or more types, a situation that can occur when the person has mutations in two or more genes, each of which causes a form of the disease. CMT is a heterogenous genetic disease, meaning that mutations in different genes can produce similar clinical symptoms.
What Causes CMT ?
CMT is caused by mutations in genes that support or produce proteins involved in the structure and function of either the peripheral nerve axon or the myelin sheath. Although different proteins are abnormal in different forms of the disease, all of the mutations mainly affect the normal function of the peripheral nerves. Gene defects in myelin cause dysfunction of the coating, which distorts or blocks nerve signals, while other mutations limit axon function and cause axonal loss.
More than 40 genes have been identified in CMT, with each gene linked to one or more types of the disease. In addition, multiple genes can be linked to one type of CMT. More than half of all cases of CMT are caused by a duplication of the PMP22 gene on chromosome 17. The gene mutations in CMT are inherited in three distinct patterns: autosomal dominant, autosomal recessive, and X-linked.
Types of CMT
The different types of CMT disease may share some symptoms, but vary by pattern of inheritance, age of onset, and whether the axon or myelin sheath is involved.
For example, CMT type 1 is caused by abnormalities in the myelin sheath, and the autosomal dominant disorder has six main subtypes.
- CMT1A results from a duplication of the gene on chromosome 17, which carries the instructions for producing the peripheral myelin protein-22 (PMP22). CMT1A is typically slowly progressive. Individuals experience weakness and atrophy of the muscles of the lower legs beginning in childhood, and later have hand weakness, sensory loss, and foot and leg problems.
- CMT1B is caused by mutations in the gene that carries the instructions for manufacturing the myelin protein zero (MPZ, also called P0), which is another critical component of the myelin sheath. CMT1B produces symptoms similar to those of CMT1A.
- Other less common causes of CMT1 result from mutations within the SIMPLE (also called LITAF), EGR2, PMP22, and NEFL genes, respectively.
CMT2 results from abnormalities in the axon of the peripheral nerve cell, rather than the myelin sheath, and is less common than CMT1. This autosomal dominant disorder has symptoms similar to those seen in CMT1, but people with CMT2 often have less disability and sensory loss compared with individuals with CMT1. The onset of CMT2 is usually in childhood or adolescence. Some types of CMT2 may have vocal cord or phrenic nerve involvement, causing speech or breathing problems.
CMT3, or Dejerine-Sottas disease, is a particularly severe demyelinating neuropathy that begins in infancy. Affected infants have severe muscle atrophy, weakness, delayed development of motor skills, and sensory problems. Symptoms may progress to severe disability, loss of sensation, and curvature of the spine. This rare disorder can be caused by mutations in multiple genes, including PMP22, MPZ, and EGR2, and can be inherited either dominantly or recessively.
CMT4, which is rare in the U.S., comprises several different subtypes of demyelinating and axonal and motor neuropathies that are inherited autosomal recessively. The mutations may affect a particular ethnic population and produce distinct physiologic or clinical characteristics. People with CMT4 generally develop symptoms of leg weakness in childhood and by adolescence may not be able to walk.
CMTX1 is the second most common form of CMT. This X-linked disease is caused by mutations in a gene that provides instructions for making the protein connexin-32, found in myelinating Schwann cells, which wrap around nerve axons and make up the myelin sheath. Males who inherit the mutated gene show moderate to severe symptoms of the disease beginning in late childhood or adolescence. Females who inherit the mutated gene typically develop milder symptoms than males or may not show symptoms at all.
Symptoms
CMT affects both sensory and motor nerves in the arms, hands, legs, and feet. The affected nerves slowly degenerate and lose the ability to communicate with their distant targets. Motor nerve degeneration results in muscle weakness and decrease in muscle bulk (i.e., atrophy) in the arms, legs, hands, or feet.
Typical early features include weakness or paralysis of the foot and lower leg muscles, which can cause difficulty lifting the foot (foot drop) and a high-stepped gait with frequent tripping or falling. Individuals also may notice balance problems. Foot deformities, such as high arches and curled toes (hammertoes), are also common in CMT. The lower legs may take on an "inverted champagne bottle" shape due to the loss of muscle bulk.
As the disease progresses, weakness and atrophy may occur in the hands, causing difficulty with fine motor skills. Degeneration of sensory nerve axons may result in a reduced ability to feel heat, cold, and touch, and the senses of vibration and position (proprioception) are often decreased.
The disease also can cause scoliosis and hip displacement. Many people with CMT develop contractures -- chronic shortening of muscles or tendons around joints, which prevents the joints from moving freely.
Muscle cramping is common. Nerve pain can range from mild to severe, and some individuals may need to rely on foot or leg braces or other orthopedic devices to maintain mobility. Some people with CMT experience tremor, and vision and hearing can also be affected.
In rare cases, breathing difficulties may occur if the nerves that control the muscles of the diaphragm are affected.
Diagnosis
The diagnosis of CMT begins with a detailed medical and family history and neurological examination. A physician will look for evidence of muscle weakness in the arms, legs, hands, and feet, decreased muscle bulk, reduced tendon reflexes, foot deformities or other orthopedic problems, and sensory loss.
Nerve conduction studies and electromyography are useful in making the diagnosis. Genetic testing can detect the most common types of CMT. In addition, a nerve biopsy of a small piece of peripheral nerve (typically from the calf) can show abnormal myelination. Specifically, formations that look like onion bulbs may be seen, which represent axons surrounded by layers of remyelinating Schwann cells.
Treatment
There is no cure for CMT, but physical and occupational therapies, braces and other orthopedic devices, and orthopedic surgery can help people cope with the disabling symptoms of the disease. In addition, pain-relief drugs can be prescribed for individuals who have severe nerve pain.
Maintaining mobility, flexibility, and muscle strength is important. Beginning a treatment program early may delay or reduce nerve degeneration and muscle weakness before it progresses to the point of disability. Physical therapy includes muscle strength training, muscle and ligament stretching, and moderate aerobic exercise. A specialized exercise program approved by the person's physician can help build stamina, increase endurance, and maintain overall health.
Many individuals with CMT disease use ankle braces or other orthopedic devices to maintain everyday mobility and prevent injury. Braces can help prevent ankle sprains by providing support and stability during activities such as walking or climbing stairs. High-top shoes or boots can help support weak ankles.
Thumb splints can help with hand weakness and loss of fine motor skills. Assistive devices should be used before disability sets in, because the devices may prevent muscle strain and reduce muscle weakening.
Michele R. Berman, MD, is a pediatrician-turned-medical journalist. She trained at Johns Hopkins, Washington University in St. Louis, and St. Louis Children's Hospital. Her mission is both journalistic and educational: to report on common diseases affecting uncommon people and summarize the evidence-based medicine behind the headlines.