SNP Shot: Genomic Insights

Central core disease (CCD) is a condition affecting skeletal muscles, the muscles responsible for movement. The main symptom is muscle weakness, which can range from very mild to severe. The degree of weakness can vary significantly, even among family members with the condition.

Most individuals with CCD experience mild, persistent muscle weakness that doesn't worsen over time. This weakness primarily affects muscles close to the body's center (proximal muscles), such as those in the shoulders, upper legs, and hips. Infants with CCD may have delayed motor skill development, impacting sitting, standing, and walking. However, most affected individuals eventually walk independently. Other symptoms can include muscle pain (myalgia) or extreme fatigue after physical activity (exercise intolerance). CCD can also be associated with misaligned eyes (strabismus), a curved spine (kyphoscoliosis), foot deformities, hip dislocation, and joint stiffness (contractures) that limit joint movement. In severe cases, infants may exhibit facial muscle weakness, significantly reduced muscle tone (hypotonia), and serious breathing difficulties that may be life-threatening.

A significant concern for individuals with CCD is the increased risk of malignant hyperthermia, a severe reaction to certain anesthesia drugs used during surgery and other procedures. Malignant hyperthermia is triggered by specific anesthetic gases, used to block pain, or when combined with muscle relaxants to temporarily paralyze patients during surgery. Individuals susceptible to malignant hyperthermia may experience a rapid heart rate (tachycardia), elevated body temperature (hyperthermia), rapid breathing (tachypnea), muscle rigidity, muscle breakdown (rhabdomyolysis), and increased acidity in the blood and tissues (acidosis). These complications can be life-threatening if not treated quickly.

The name "central core disease" comes from the presence of abnormal areas, called central cores, found within skeletal muscle cells. These cores are typically located in the center of the cell but can also be at the edges or span the length of the cell. They are only visible under a microscope. These cores are often found in cells that have few or no mitochondria, the structures responsible for energy production within cells. While the presence of central cores aids in diagnosing CCD, their exact role in causing muscle weakness and other symptoms remains unclear.

Inheritance:

CCD is most commonly inherited in an autosomal dominant pattern. This means that only one copy of a mutated gene in each cell is sufficient to cause the condition. In some instances, an affected person inherits the mutation from a parent who also has CCD. In other cases, the condition arises from a new gene mutation in an individual with no family history of the disorder. Less frequently, CCD is inherited in an autosomal recessive pattern. This means that both copies of the gene in each cell must have mutations for the condition to develop. In autosomal recessive inheritance, each parent typically carries one copy of the mutated gene but does not exhibit signs or symptoms of CCD. However, individuals carrying one mutation in the RYR1 gene may have a higher risk of malignant hyperthermia.