Ryanodine receptor type 1-related disorder (RYR1-RD) is the most common subgroup of congenital
myopathies with a wide phenotypic spectrum ranging from mild
hypotonia to lethal fetal akinesia. Genetic testing for
myopathies is imperative as the diagnosis informs counseling regarding prognosis and recurrence risk, treatment options, monitoring, and clinical management. However, diagnostic challenges exist as current options are limited to clinical suspicion prompting testing including: single gene sequencing or familial variant testing, multi-gene panels, exome, genome sequencing, and invasive testing including muscle biopsy. The timing of diagnosis is of great importance due to the association of RYR1-RD with
malignant hyperthermia (MH). MH is a hypermetabolic crisis that occurs secondary to excessive
calcium release in muscles, leading to systemic effects that can progress to
shock and death if unrecognized. Given the association of MH with pathogenic variants in
RYR1, a diagnosis of RYR1-RD necessitates an awareness of medical team to avoid potentially triggering agents. We describe a case of a unique fetal presentation with bilateral diaphragmatic eventrations who had
respiratory failure, dysmorphic facial features, and profound global
hypotonia in the neonatal period. The diagnosis was made at several months of age, had direct implications on her clinical care related to anticipated need to long-term
ventilator support, and ultimately death secondary an
arrhythmia as a result of suspected MH. Our report reinforces the importance of having high suspicion for a genetic syndrome and pursuing early, rapid exome or genome sequencing as first line testing in
critically ill neonatal intensive care unit patients and further evaluating the pathogenicity of a variant of uncertain significance in the setting of a myopathic phenotype.