PO61 Novel mutation in the KCNH2 gene in a patient with long QT syndrome presenting with cardiac arrest

Sudden cardiac arrest (SCA) in young adults is a devastating event, and its underlying causes should be thoroughly explored to prevent recurrence. Long QT Syndrome (LQTS) is a cardiac channelopathy that affects approximately 1 in 2,500 individuals in the general population and is a cause of SCA in otherwise healthy individuals, as it could originate potential fatal ventricular tachyarrhythmias. LQTS 1, 2 and 3 are the most common forms of the disease and are associated with mutations in the KCNQ1, KCNH2 and SCN5A genes respectively. Although more than 900 mutations related to LQT2 have already been reported, there are novel mutations yet to be discovered, which is essential to further clarify the pathogenesis of LQT2. We report the case of a 32-year-old woman, 3 months postpartum, with a history of syncope episodes since childhood, typically occurring at rest, and a family history of sudden cardiac arrest at young age (her father at the age of 40 years-old). She was not taking any medication. She presented with SCA in ventricular fibrillation, which occurred after she woke up startled by a noise at home. The first electrocardiogram following successful resuscitation showed sinus rhythm and a corrected QT interval of 542 ms. Laboratory analysis revealed hypomagnesemia, hypophosphatemia, and hypocalcemia. The echocardiogram at admission revealed moderately depressed left ventricular function with diffuse wall motion abnormalities, which improved during hospitalization. The remaining initial etiological workup was negative. During the first 24 hours of hospitalization, the patient experienced recurrent VF and polymorphic ventricular tachycardia, associated with cardiogenic shock, which improved after ionic replacement, dobutamine, and noradrenaline infusion. The QT interval prolongation persisted despite correction of electrolyte disturbances. Cardiac magnetic resonance performed 17 days after the SCA revealed preserved left ventricle function with unspecific subendocardial late gadolinium enhancement at the interventricular septum, particularly on the mid-basal segments. The patient was treated with an oral beta-blocker and an implantable cardioverter-defibrillator for secondary prevention. She remained asymptomatic with no device therapies. Consultation ECG revealed persistence of QTc prolongation. Genetic testing identified the presence of the c.2063_2066dup p.(Pro690Aspfs*34) variant in the KCNH2 gene, in heterozygosity, which leads to the formation of a premature termination codon, and was classified as likely pathogenic, associated with LQTS. This variant had not been previously described in the literature. This case highlights the importance of maintaining a high level of clinical suspicion and the role of genetic testing when evaluating a patient who experienced ventricular fibrillation without an obvious cause. It also provides the first clinical evidence that the Pro690Aspfs*34 variant is likely pathogenic and associated with LQTS type 2.