CONGRESS ABSTRACT

Introduction: Calcium release deficiency syndrome, recently identified, is a ryanodinopathy caused by mutations in the Ryr2 gene that result in loss of function of the gene. Clinically, it is associated with the risk of polymorphic VT and sudden death. Arrhythmias are not triggered by physical activity and can occur without warning signs. Some studies have demonstrated the utility of the intracavitary electrophysiological study with LBLPS stimulation protocol to identify high-risk subjects, who could benefit from flecainide therapy. Clinical case: C.M., a 9-year-old child, comes to our observation. At the age of 3 years, intellectual disability, language disorder, craniofacial dysmorphism were found. He performed karyotype, analysis for fragile X syndrome and SNIP-array , that resulted normals. He then performed a clinical exome that diagnosed a pathogenic variant of the NAA15 gene, compatible with the clinical picture, and an unexpected variant c.1477-1G>C, probably pathogenic, affecting the Ryr2 gene. This autosomal dominant variant, inherited from the mother, involves a splicing site, suggesting a possible loss-of-function effect. From a clinical point of view, the patient has never presented documented arrhythmias, neither syncope nor heart palpitation. His maternal grandmother and maternal great-grandmother died suddenly at the age of 50 and 59. The mother, who is a carrier of the variant, is asymptomatic. ECG and echocardiogram of the child are normal. On Holter and exercise testing absence of ventricular extrasystoles. An intracavitary electrophysiological study is performed, with programmed ventricular pacing with single, double and triple extra stimulus and with LBLPS protocol in apex and right ventricular outflow tract. No ventricular arrhythmias are induced. The patient is started to follow up. Conclusions: The increasing use of maximal genomic sequencing techniques such as clinical exome exposes to the risk of incidental findings and variants of uncertain significance. Calcium release deficiency syndrome may not manifest with ECG abnormalities or arrhythmias on Holter and exercise testing and may present with sudden death. Further studies are needed to define how risk stratification can be carried out in these patients and which may be the role of the electrophysiological study and the possible usefulness of a drug therapy.