Case Report: Nadolol-mexiletine combination therapy for refractory neonatal long QT syndrome: a case series beyond sodium channelopathies.

Neonatal long QT syndrome (LQTS) is associated with substantial mortality and poses significant therapeutic challenges, particularly in cases refractory to beta-blocker monotherapy. Mexiletine is established for LQT3 caused by SCN5A gain-of-function mutations, but its role in potassium-channel-related neonatal LQTS is limited. We present two neonates with LQTS refractory to nadolol monotherapy: one with a heterozygous pathogenic SCN5A c.5287G > A (p.Val1763Met) variant (LQT3), and one with a heterozygous KCNQ1 exon 13-15 deletion (LQT1). In both cases, addition of mexiletine to nadolol was associated with QTc shortening, reduction in ectopic burden, and resolution of 2:1 atrioventricular conduction in Case 1; no adverse events were documented. We describe the clinical experience descriptively, without proposing a generalizable mechanistic claim regarding mexiletine outside LQT3. No ICD implantation was performed and no deaths occurred during follow-up. These observations support further evaluation of mexiletine as an adjunct in refractory neonatal LQTS, including non-LQT3 subtypes.