Structural changes and contractility in muscle assessed by magnetic resonance imaging in individuals with ryanodine receptor 1-related rhabdomyolysis or myalgia.

Introduction/aims: Ryanodine receptor 1 (RYR1)-related myopathies associated with variants in the RYR1 gene present with a wide range of symptoms and severity. Two of the milder phenotypes associated with dominant pathogenic variants in RYR1 are rhabdomyolysis and myalgia. Only a few studies have investigated the muscle function and structure of individuals with RYR1-related rhabdomyolysis/myalgia objectively, showing inconsistent results. This study aimed to describe structural changes and contractility of muscles in individuals with RYR1-related rhabdomyolysis/myalgia.

Methods: We investigated 15 individuals with dominant variants in the RYR1-gene and compared them with 15 age-, sex-, and body mass index (BMI)-matched controls using MRI, stationary isokinetic dynamometry, and comprehensive clinical evaluation.

Results: No significant differences were found between individuals with RYR1-related rhabdomyolysis/myalgia and healthy controls in peak torque, fat fraction, cross-sectional area, contractile cross-sectional area, or contractility (p > .05) in muscles of the lower back (MRI data only), thigh, or calf. On clinical examination, three individuals exhibited weakness in hip or back extension on the Medical Research Council (MRC) test and eight had muscle hypertrophy. Individuals with weakness were not hypertrophic.

Discussion: Most individuals with RYR1-related rhabdomyolysis/myalgia have close to normal strength, and normal fat fraction and contractility of muscles, and therefore constitute a mild phenotype of RYR1-related myopathies.