Introduction
The skeletal muscle system is one of the body’s major organ systems, along with the cardiac and smooth muscle systems. It attaches to the bones through tendons and is responsible for all body movements. The skeletal muscles need to contact and relax in a coordinated manner to achieve proper movements, which depends on the concentration of calcium ions in the muscle cells. In the skeletal muscle cell membrane, ryanodine receptors (protein molecules) are present, which form channels (RYR1 channels), which on activation, release the calcium ions from storage in the sarcoplasmic reticulum into the cell fluid. This, in turn, increases the concentration of calcium ions in the muscles, resulting in the proper contraction and relaxation of the skeletal muscles.
What Is Central Core Disease?
The central core disease is also called central core myopathy. It is called so because of the disorganized areas at the center of the skeletal muscle cells, sometimes at the edges or along the length of the cells, observed under a microscope. Absence or decreased mitochondria (cells that produce energy) may also be noted in some cases. It was first described by Shy GM and Magee KR in 1956. It is a rare muscular disorder present from birth in some individuals (an autosomal dominant genetic disorder) and mainly affects the skeletal muscles (muscles that help in movement). It is usually diagnosed in infancy, but in most cases, it is asymptomatic until adulthood or middle age. The severity may vary, even among the members of the same family. It may affect males and females equally, and the exact incidence and prevalence are unknown.
What Are the Causes of Central Core Disease?
The main cause of central core disease is the mutation of the RYR1 gene, which results in the abnormal flow of calcium ions within the skeletal muscle cells. Calcium ions that are unable to pass through the receptor channels leak slowly and cause disruption in the flow, leading to abnormal contraction and relaxation, resulting in muscle weakness. It mainly affects the core muscles or the muscles near the center of the body, like the muscles of the hips, upper legs, etc.
What Are the Signs and Symptoms of the Central Core Disease?
Some of the signs and symptoms include:
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Muscle pain or myalgia, muscle cramps, and severe fatigue.
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Decreased muscle tone (hypotonia or floppiness) and weakness.
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Delay in development affects children's motor skills like sitting, standing, walking, etc.
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Weakness of facial, shoulder, upper legs, and hip muscles.
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Skeletal disorders like scoliosis and hip dislocation.
What Are the Risk Factors Associated With Central Core Disease?
Some of the risk factors associated with the central core disease include:
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Patients with the central core disease have an increased risk of developing malignant hyperthermia, which is characterized by a severe reaction to drugs used during surgery or other invasive treatment procedures. It occurs mainly in response to anesthetic gasses, which are given as a single or in combination with muscle relaxants to block the pain sensation during the procedure. It results in increased heart rate (tachycardia), increased body temperature (hyperthermia), abnormal breathing, increased acid levels in the body, and breakdown of muscle fibers. It can be a life-threatening condition and requires prompt management.
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The central core disease is also associated with joint deformities, hip dislocation, foot deformities, the rounded upper portion of the back that curves to one side (kyphoscoliosis), and also, eyes that do not look in the same direction (strabismus).
How Is the Central Core Disease Diagnosed?
The diagnosis of the central core disease is based on the patient's history, family history, and physical findings, along with blood tests, muscle biopsy, electromyography, nerve conduction velocity studies, etc. Blood tests usually show normal or slightly increased creatinine kinase enzyme levels, except during a malignant hyperthermia crisis. Other tests include:
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Electromyography (EMG): It is a test procedure that records the electrical activity in skeletal muscles during rest and activity. An electrode is inserted into the muscle, which reads the electrical signals and displays them in the monitor called an oscilloscope. In the case of central core disease, some muscle fibers show an unusually short duration of activity with low amplitude, which may confirm the diagnosis.
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Nerve Conduction Studies: During this test, the motor and sensory nerves are electrically stimulated to assess the ability and the speed of conduction of nerve impulses. It is usually found to be normal in most cases of the central core disease.
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Muscle Biopsy: This procedure involves removing a small sample of muscle tissue, and special staining is done (histochemistry) and observed under a microscope. On examination, the biopsy reveals dense ill-defined areas located in the central portion of the muscle fibers, which contain myofibril material (thin strands of muscle fibers). The altered areas confirm a lack of enzyme activity compared to the surrounding normal fibers. The absence of mitochondria, the main source of energy for the cells, may also be seen in some cases.
How Is Central Core Disease Managed?
A curative treatment is not available for the central core disease, and the management includes supportive and symptomatic treatment. It requires the combined support of pediatricians, orthopedists, physicians, physiotherapists, and psychiatrists. Some of the treatment methods:
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In the case of infants with weak muscles, adaptive seating with comfortable head and neck support is recommended, and tube feeding is advised to maintain the nutritional intake. The use of special braces or supporting devices is recommended to prevent falls and injury.
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As the patients are at high risk of developing malignant hyperthermia, care should be taken in administering anesthetics during surgical procedures. It should be carried out only under the supervision of an anesthesiologist.
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Genetic counseling is advised for the patients and their family members.
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Physiotherapy may be helpful in most cases by preventing the development of contractures, maintaining breathing capacity, and delaying the development of spine curvature.
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Spinal surgery is preferred in some severe cases, involving realigning the spinal column by inserting rods, screws, or wires.
Conclusion
The central core disease is an autosomal dominant disorder that affects the skeletal muscles due to the mutation of the RYR1 gene. It is characterized by decreased muscle tone, weakness, and delayed motor skills in the case of infants. A muscle biopsy and electromyography usually confirm the diagnosis. Curative treatment is not available for this condition and is managed by supportive and symptomatic treatment through physiotherapy and genetic counseling.
