Multiminicore disease

Multiminicore disease is a rare muscle disorder characterized by skeletal muscle weakness and the presence of small, disorganized regions called minicores within muscle cells.

Overview

Multiminicore disease primarily affects skeletal muscles, causing weakness that ranges from mild to life-threatening. The condition is named for the "minicores"—small, disorganized areas found in muscle cells when viewed under a microscope—which are often present in cells with few or no mitochondria.

Types

There are four recognized forms of the disease:

• Classic form: Accounts for 75% of cases; involves weakness in the torso and neck, "floppy" infants, and potential respiratory issues or spinal curvature (scoliosis).
• Progressive form with hand involvement: Involves muscle weakness and joint laxity in the arms and hands, often with exercise intolerance.
• Antenatal form with arthrogryposis: Characterized by rigid joints throughout the body and distinctive facial features.
• Ophthalmoplegic form: Characterized by paralysis of the eye muscles, leading to abnormal eye movements and droopy eyelids.

Causes & Risk Factors

Variants in the SELENON and RYR1 genes cause about half of all cases. SELENON variants are linked to the classic form and may affect muscle formation and calcium balance. RYR1 variants disrupt the ryanodine receptor 1 protein, which regulates calcium release in muscle cells, preventing normal contraction. Individuals with these variants may also be at risk for malignant hyperthermia, a severe reaction to certain anesthetic gases used during surgery.

Inheritance

This condition is inherited in an autosomal recessive pattern, meaning both copies of the gene in each cell have variants. Parents of an affected individual typically carry one copy of the altered gene but do not show symptoms.