key: cord-0995269-ozpiyknu authors: Mahajan, Asha M.; Itan, Yuval; Cerrone, Marina; Horowitz, James; Borneman, Linda; Chinitz, Larry; Jankelson, Lior title: Sudden Cardiac Arrest in a Patient With Mitral Valve Prolapse and LMNA and SCN5A Mutations date: 2021-02-17 journal: JACC Case Rep DOI: 10.1016/j.jaccas.2020.11.046 sha: e636312cf724ab2716d0e43a9e376ebde9dcfd00 doc_id: 995269 cord_uid: ozpiyknu Bileaflet mitral valve prolapse (Bi-MVP) is associated with increased risk for cardiac arrest. We describe a patient who presented after a cardiac arrest with Bi-MVP and variants in Lamin A/C (LMNA) and the sodium channel alpha-subunit 5a (SCN5A). Genetic variants may be the culprit for arrhythmogenesis in Bi-MVP patients. (Level of Difficulty: Intermediate.) tricular fibrillation (VF). She was shocked to sinus rhythm on the field, and upon arrival to the hospital, she was tachycardic and had a systolic murmur. Her electrocardiogram (ECG) showed sinus tachycardia with ST-segment depressions in the lateral leads and a prolonged corrected QT (QTc) interval of 576 ms ( Figure 1A) . No medication exposure was identified. The patient had a history of heart murmur since childhood, which was not evaluated, and hypertension for which she was taking amlodipine-benazepril daily. Her paternal grandfather died suddenly at the age of approximately 30 years from an unknown cause. There was no information about her maternal side. She has 3 brothers and 1 sister between the ages of 24 and 41 years; all are alive but not available for clinical investigation. The initial differential diagnosis for the etiology of her VF included Bi-MVP syndrome, viral-induced myocarditis, and long QT syndrome (LQTS). To discuss the role of genetic variants in patients with Bi-MVP that could be the primary cause for ventricular arrhythmia rather than MVP alone. To highlight the use of advanced interpretation tools to further analyze genetic variants of uncertain significance in the setting of limited segregation data. The patient was admitted to the intensive care unit and underwent therapeutic hypothermia for 24 h. Bi-MVP has been associated with an increased risk of ventricular arrhythmias and cardiac arrest. We discuss a patient who had presented after an out-of-hospital VF arrest found to have Bi-MVP with LV dysfunction and LV inferobasal wall fibrosis. Genetic variants in LMNA and SCN5A were determined to be of uncertain significance by commercial interpretation. Family screening is essential for interpretation of suspicious variants. In the absence of such segregation data, we used an advanced prediction algorithm to adjudicate variants. We conclude that Bi-MVP with sudden cardiac arrest should not preclude genetic testing and that interpretation of discovered variants should be Sudden death in primary mitral valve prolapse Malignant bileaflet mitral valve prolapse syndrome in patients with otherwise idiopathic out-ofhospital cardiac arrest Myocardial fibrosis in patients with primary mitral regurgitation with and without prolapse Hybrid positron emission tomography/ magnetic resonance imaging in arrhythmic mitral valve prolapse Morphofunctional abnormalities of mitral annulus and arrhythmic mitral valve prolapse Dilated cardiomyopathy produced by lamin A/C gene mutations Clinical spectrum of SCN5A mutations: long QT syndrome, Brugada syndrome, and cardiomyopathy Prevalence and clinical phenotype of concomitant long QT syndrome and arrhythmogenic bileaflet mitral valve prolapse CADD: predicting the deleteriousness of variants throughout the human genome The mutation significance cutoff: gene-level thresholds for variant predictions Assessment is based on a combination of patient clinical findings, combined annotation dependent depletion, and variant frequency.CADD ΒΌ Combined Annotationperformed by experts using expanded tools beyond commercial kits (Central Illustration). The authors have reported that they have no relationships relevant to the contents of this paper to disclose.