SNP Shot: Genomic Insights

Multiminicore disease is a condition that primarily affects the skeletal muscles, which are responsible for movement. This disease leads to muscle weakness and a range of related health issues, varying in severity from mild to life-threatening.

Researchers have identified at least four types of multiminicore disease, each characterized by distinct signs and symptoms. These types include the classic form, the progressive form with hand involvement, the antenatal form with arthrogryposis, and the ophthalmoplegic form.

The classic form is the most common, accounting for about 75% of cases. It causes muscle weakness that starts in infancy or early childhood. The muscles of the torso and neck (axial muscles) are most severely affected, with arm and leg muscles being less involved. Affected infants may appear "floppy" (hypotonic) due to muscle weakness and may experience difficulties with feeding. Motor skill development, like sitting, standing, and walking, may be delayed. The muscles of the ribcage and spine become stiff, and breathing muscles are weak, leading to potentially severe or life-threatening respiratory problems. Almost all children with the classic form develop scoliosis, an abnormal curvature of the spine, which appears in childhood and worsens over time.

The progressive form with hand involvement results in muscle weakness and joint laxity (looseness) in the arms and hands. Individuals with this form may experience muscle pain (myalgia) or extreme fatigue following physical activity (exercise intolerance). This form represents about 10% of multiminicore disease cases.

The antenatal form with arthrogryposis is characterized by stiff, rigid joints throughout the body (arthrogryposis) and distinctive facial features. Weakness in the breathing muscles can cause respiratory problems. This form also accounts for approximately 10% of multiminicore disease cases.

The ophthalmoplegic form of multiminicore disease is defined by paralysis of the eye muscles (external ophthalmoplegia), leading to abnormal eye movements and droopy eyelids (ptosis). This form can also cause weakness in proximal muscles, which are those closest to the center of the body, such as the upper arms and legs. The ophthalmoplegic form accounts for 5 to 10% of multiminicore disease cases.

Many individuals with multiminicore disease are at a higher risk of developing malignant hyperthermia, a severe reaction to certain drugs used during surgery and other invasive procedures. Malignant hyperthermia is triggered by some anesthetic gases, used to block pain sensation, either alone or in combination with a muscle relaxant used to temporarily paralyze a person during surgery. If given these drugs, individuals at risk may experience a rapid increase in heart rate (tachycardia) and body temperature (hyperthermia), rapid breathing (tachypnea), muscle rigidity, muscle fiber breakdown (rhabdomyolysis), and increased acid levels in the blood and tissues (acidosis). Untreated, malignant hyperthermia can be life-threatening.

Multiminicore disease is named for the presence of small, disorganized areas called minicores within the skeletal muscle cells of many affected individuals. These abnormal areas are visible only under a microscope. Minicores are frequently found in cells with few or no mitochondria, the energy-producing centers of cells. While the presence of minicores can aid in diagnosis, their exact relationship to muscle weakness and other features of the condition remains unclear.

Inheritance:

The inheritance pattern of this condition is autosomal recessive. This means that an individual must inherit two copies of the mutated gene (one from each parent) to develop the condition. The parents, who each carry one copy of the mutated gene, typically do not show signs or symptoms of the condition.