Ryanodine Receptor 1-Related Myopathies: Diagnostic and Therapeutic Approaches
November 7, 2018
Ryanodine Receptor 1-Related Myopathies: Diagnostic and Therapeutic Approaches

Authors: Tokunbor A. Lawal, Joshua J. Todd, Katherine G. Meilleur


Read the full article here

Ryanodine receptor type 1-related myopathies (RYR1-RM) are the most common class of congenital myopathies. Historically, RYR1-RM classification and diagnosis have been guided by histopathologic findings on muscle biopsy. Main histological subtypes of RYR1-RM include central core disease, multiminicore disease, core–rod myopathy, centronuclear myopathy, and congenital fiber-type disproportion. A range of RYR1-RM clinical phenotypes has also emerged more recently and includes King Denboroughsyndrome, RYR1 rhabdomyolysis-myalgia syndrome, atypical periodic paralysis, congenital neuromuscular disease with uniform type 1 fibers, and late-onset axial myopathy. This expansion of the RYR1-RM disease spectrum is due, in part, to implementation of next-generation sequencing methods, which include the entire RYR1 coding sequence rather than being restricted to hotspot regions. These methods enhance diagnostic capabilities, especially given historic limitations of histopathologic and clinical overlap across RYR1-RM. Both dominant and recessive modes of inheritance have been documented, with the latter typically associated with a more severe clinical phenotype. As with all congenital myopathies, no FDA-approved treatments exist to date. Here, we review histopathologic, clinical, imaging, and genetic diagnostic features of the main RYR1-RM subtypes. We also discuss the current state of treatments and focus on disease-modulating (nongenetic) therapeutic strategies under development for RYR1-RM. Finally, perspectives for future approaches to treatment development are broached.

Keywords: RYR1 . Myopathies . Therapeutics . Central core disease . N-acetylcysteine . Rycal . 4PBA . Salbutamol

Close close
Newsletter Registration