n.e.: not evaluated.
DISCUSSION
Brugada syndrome (BrS) was first described in 1992 as a new electrical heart disease (16). This is characterized by episodes of syncope or SCD in individuals <45 years of age affected by the pathology, and the ECG shows typical elevation of the ST segment in the right precordial leads without the presence of ischemia or structural heart disease (12). However, BrS is definitively diagnosed when elevation of the ST segment is observed, and more than one right precordial ligament in the presence or absence of a sodium channel blocking agent (9).
As the most recurrently observed channelopathy the BrS was also more identified in the studies pointed out in this review in children and adolescents. The diagnosis of BrS can be difficult in childhood, as it usually manifests as dysrhythmia or SCM (14), in addition, children and adolescents with BrS may have a normal resting ECG, however the presence of fever during a symptomatic episode of the disease could unmask the disease-related changes on the ECG (12, 17). In this sense, a previous study of pediatric cases with BrS, approximately half of the syncope events were precipitated by fever (18).
Thus, Besli et al. (2018) in a case study pointed out in this review also evidenced the presence of fever in the patient who presented minor polymorphic deletion in the heterochromatic region of the long arm of the Y chromosome and SCN5A polymorphism with point mutation in exon 11. Interestingly, although there was no family history consistent with BrS, the patient’s parents and sibling presented a mutation or polymorphism similar to that of the patient. Possibly associated with heterozygosis and mild or asymptomatic phenotype of family members.
Moreau et al. (2018) also identified mutations related and consistent with SBr in their case study with an 11-year-old child with a heterozygous missense mutation SCN5A and a 14-year-old teenager with a homozygous missense mutation in the compound SCN5A, the individuals were unrelated and both suffered a stroke. In this type of mutation, there is an alteration of one of the DNA bases, in such a way that the nucleotide triplet of which it is part changes, starting to encode an incorrect amino acid with altered function of the synthesized protein (19).
Still on the study by Moreau et al. (2018) the clinical phenotype associated with the first mutation includes several cardiac dysfunctions such as atrial dysfunctions, including sinus node syndrome, atrial arrest and atrial arrhythmias, as well as conduction system disorders. In the second mutation, the E1053K mutation is observed, which is associated with dysfunctions in the ankirin binding protein of Nav1.5, promoting a cardiac arrhythmia caused by altered Nav1.5 function (20). The E1053K mutation eliminates the binding of Nav1.5 to ankirin-G and prevents the accumulation of Nav1.5 at cell surface sites in ventricular cardiomyocytes (20). These mutations that significantly alter the activity and production of important proteins related to cardiomyocyte excitability, they are considered mutations that promote fatal arrhythmias (21). In this case study, the author also associates the presence of mutations in events related to stroke in children and adolescents.
Baskar et al. (2014) observed in his case study changes related to a rare P1048SfsX97 frame mutation that, although it has not yet been reported, this mutation results in loss of sodium channel function, possibly associated with Type 1 Brugada Syndrome. study, the child also had a missense T220I mutation (c.659 C> T). Unlike the previous mutation, it was previously reported and functionally characterized as having multiple effects on the sodium channel, causing general loss of sodium channel function and function of the sinoatrial node pacemaker (22, 23).
We can also observe that the SLC12A3 A588V mutation and the SCN5A H558R polymorphism, the only dysfunctions associated with long QT syndrome in the studies included in this review, imply low serum levels of potassium and magnesium, which contribute significantly to the prolongation of the QT interval (24). Although the clinical manifestations of this dysfunction present a mild phenotype and with a good prognosis, life-threatening events can occur even in a rare way (25). Therefore, it is important to monitor and correct serum electrolyte disturbances to prevent ventricular arrhythmias and sudden death in patients with the condition. In the study by Tsukakoshi et al. (2018) the author describes that the H558R polymorphism increases the level of expression of the sodium channel and can therefore affect the initial phase of the action potential, however its effects on the QT interval in the present case were unclear.
Thus, the studies included in this review demonstrate the importance of better assessment and elucidation of mutations and polymorphisms related to the cardiovascular system of children and adolescents, once in the last decades an increasing number of studies have described the physiology and changes at the molecular level these dysfunctions, however, few studies have explored the prevalence of these pathologies and their implications in this population. Given this, we found mostly case studies that addressed the theme, but none of them carried out longitudinal monitoring of the individuals reported in the research after diagnosis of the pathologies.
CONCLUSION
In this literature review, it is possible to observe the main hereditary canalopathies found in children and adolescents from 7 to 14 years old, these being Brugada Syndrome Type 1 and Long QT Syndrome. As the most frequently observed channelopathy, BrS was also more identified in children and adolescents, characterized by episodes of syncope or sudden cardiac death. The second mutation shows clinical manifestations with a mild phenotype and good prognosis, although it is necessary to monitor and correct serum electrolyte disturbances to prevent ventricular arrhythmias and, consequently, sudden death in patients with the pathology.