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.