Pancreatitis in RYR1-related disorders

Mutations in RYR1 encoding the ryanodine receptor (RyR) skeletal muscle isoform (RyR1) are a common cause of inherited neuromuscular disorders. Despite its expression wide range tissues, non-skeletal manifestations associated with mutations have only been rarely reported.Here, we report three patients diagnosis Central Core Disease (CCD), King-Denborough Syndrome (KDS) and Malignant Hyperthermia Susceptibility (MHS), respectively, who addition to their (putative) RYR1-related disorder also developed symptoms signs acute pancreatitis. In two patients, episodes were recurrent, severe multisystem involvement sequelae.RyR1-mediated calcium signalling plays an important role normal pancreatic function but has critically implicated pathophysiology pancreatitis, particularly bile acid- ethanol-induced forms. Findings from relevant animal models indicate that damage these conditions may be ameliorated through administration specific RyR1 antagonist dantrolene other compounds modifying metabolism including signalling.These observations suggest gain-of-function variants at increased risk developing condition which should therefore considered health surveillance such individuals.