MISSENSE MUTATIONS IN S6 SEGMENT OF IV DOMAIN OF SCN5A CHANNEL CAUSING A CONGENITAL LONG QT SYNDROME WITH AV BLOCK AND TORSADES DE POINTES IN TWO NONRELATED NEONATES

INTRODUCTION:LQTS is a genetically heterogeneous disorder characterized by QT prolongation, ventricular arrhythmias and SCD. Neonatal manifestation is, however, rare. We review the clinical course of two cases of LQTS presenting immediately after birth.
CASE 1: Eutrophic baby manifested with bradycardia - 60 bpm 24 hours after the birth. QTc 720 ms with functional 2nd degree 2:1 AV block was recorded and an urgent epicardial VVI pacemaker was implanted. Non-sustained TdP occurred during the procedure and was treated with continuous infusion of lidocaine and esmolol. The baby was discharged home on propranolol in sinus rhythm with QTc 477 ms. Unfortunately, the child died suddenly at home. Genetic testing revealed a de novo SCN5A gene mutation causing LQTS type 3.
CASE 2: 3-days-old baby was admitted to our hospital with a heart rate of 70 bpm, QTc 550 ms, functional 2nd degree 2:1 AV block and non-sustained TdP. An epicardial VVI pacemaker was implanted, infusion of lidocaine and esmolol was initiated and gradually converted to oral treatment with propranolol and mexiletine according to the phenotype presentation. Subsequent ECGs showed sinus rhythm with QTc 430ms. Genetic evaluation confirmed also a de novo mutation in SCN5A gene. CONCLUSION: The type-specific diagnosis of long QT syndrome can direct physicians to the individualized therapy. LQTS type 3 was suspected in patient No 2 and a potentially life-saving sodium channel blocker therapy was started. In both patients, genetic evaluation subsequently revealed a de novo SCN5A mutation. Both of the variants were localized in close proximity in the same transmembrane segment S6 of the sodium channel domain IV.

Acknowledgement: Supported by Ministry of Health of the Czech Republic, grant nr. NV18-02-00237. All rights reserved." And by G90039 (IKEM,institutional support) and NF-CZ11-PDP-3-003-2014