Congenital Long QT Syndrome (LQTS) is one of the main causes of sudden cardiac death (SCD) in the pediatric age group, with a prevalence of approximately one case for every 2,000 newborns. The most prevalent inheritance is dominant, with the typical phenotype associated with cardiac manifestations.¹

The genetic alteration of LQTS is multigenic, with 17 main genes, and in 80% of the cases, it identifies: KCNQ1 (LQTL1), KCNH2 (LQTL2), and SCN5A (LQTL3).² The LQTS type 2 (LQTS2) subtype alters the expression of potassium channels in myocytes, causing electrical instability and ventricular arrhythmias.³ The most common arrhythmia is Torsades de Pointes (TdP), a type of polymorphic ventricular tachycardia, which can lead to syncope, seizures, and sudden death.¹

The therapeutic objectives are to reduce the QT interval and maintain the sinus rhythm. Beta blockers are the most commonly used medication to treat this condition. In cases of refractoriness, other drugs or left cardiac sympathetic denervation (LCSD) can be considered.¹

This article reports on the case of an infant with LQTS2 who shows early manifestations, discussing relevant aspects about diagnosis and treatment, in addition to our experience of using mexiletine associated with beta-blocker therapy to control arrhythmias.

Patients with congenital LQTS may be asymptomatic for a long period, resulting in underdiagnosis and underestimation of incidence. Symptoms of LQTS2 begin during puberty and, among symptomatic patients, one in four presents an arrhythmia that triggers the syndrome or sudden death. In the present case report, the patient presented atypical manifestations from the ECG and clinical perspectives, which began at one month of age.⁴

The clinical picture of the syndrome is triggered by specific triggers depending on the genotype. Patients with LQTS2 develop arrhythmias triggered by abrupt sound stimuli, fright, and emotional stress. In LQTS3, they are triggered during sleep and rest, as occurred in the patient in this study.⁵

The ECG findings, in addition to the long QT interval, indicate morphological alterations in the T wave. In LQTS2, the T wave is bifid or notched, asymmetrical, and of low amplitude, which was not characteristic of the patient; in LQTS3, the T wave has a later peak. Although these alterations are found, they are nonspecific and increasingly less valued.⁶

In the first moment, the investigation of secondary causes is extremely important. Next, serial ECG, clinical parameters, family history, and the Schwartz Score are assessed. The scoring of this score defines the probability of the disease; a value of ≥ 3.5 points indicates a high probability.⁷

The therapy of choice is beta-blockers, at the maximum dose tolerated by the patient.⁴ In LQTS2, these drugs are less effective in monotherapy and can be optimized with magnesium and potassium-sparing diuretics.¹ Mexiletine may be an alternative in refractory cases. A case of this nature would refer to an antiarrhythmic that acts by selectively suppressing sodium channels in myocytes, corroborating its therapeutic efficacy in LQTS3.

Bos et al.⁸ developed a retrospective cohort with 12 patients with LQTS2 using beta-blockers and associated with mexiletine, to assess the control of the syndrome. The analysis was performed using serial ECG, comparing QTc values before and after medication. A 65ms reduction in QTc value was observed in 8 patients and a 90ms reduction in the others. They concluded that pharmacological targeting of the late physiological sodium current may provide additional therapeutic efficacy to beta-blocker therapy in patients with LQTS2.

A meta-analysis that evaluated six studies with 217 patients with LQTS, using mexiletine, confirmed a reduction in the QTc interval in LQTS2 by 40 ms and an absence of cardiac events, especially TdP during the study, confirming the efficacy of the drug in this genotype, with the need for further studies to understand its action.⁹

Therefore, although the therapeutic approach using mexiletine in LQTS2 is not fully described in the literature, its use showed significant efficacy in controlling the QTc interval to values below the proarrhythmic threshold in the patient. After the administration of mexiletine, the QTc remained below 500 ms, and an absence of arrhythmias was observed.