Abstract:
Cardiac channelopathies are a heterogeneous group of inherited cardiac
diseases that are associated with mutations in the genes that encode the
expression of cardiac ion channels. In view of this, it can be mentioned
that the main hereditary arrhythmias in children and adolescents, caused
by dysfunction of the ion channels are Brugada Syndrome (BrS) and Long
QT Syndrome (LQTS). However, few studies address the physiological
effects of these conditions on children and adolescents. Thus, the aim
of this study is to describe the mutation phenotype related to
voltage-gated sodium channels in children and adolescents. A search was
performed in the literature of Pubmed, Scielo and Google scholar. The
search was limited to articles written in English in the last 5 years,
so articles published between January 2014 and January 2019 were
included. Among 2196 studies identified through a systematic literature
review, thirty studies related to the theme were identified for complete
review and after applying exclusion criteria 4 articles were included in
the results of this research. As the most frequently observed
channelopathy, BrS was also more identified in children and adolescents,
characterized by episodes of syncope or sudden cardiac death. LQTS 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.
Palavras-chaves Cardiac channelopathies; Voltage-dependent
sodium channels; Children; Adolescents.
1. INTRODUCTION
Ion channels are a group of multiple proteins that cross the membrane
forming pores or channels (1,
2), these proteins are responsible for
ionic exchanges between the intracellular and extracellular media,
however in some cases the presence of genetic mutations in these
channels, also called cardiac channelopathies, are associated with
increased risks of cardiac arrhythmias and greater susceptibility to the
occurrence of syncope and seizures (3),
although, for the most part, there are no underlying structural heart
defects (4).
Cardiac channelopathies are a heterogeneous group of inherited heart
diseases that are associated with mutations in the genes that encode the
expression of cardiac ion channels, these being the Na, K + and Ca2 +
channels or proteins that regulate their function
(5-7).
In this sense, triggered arrhythmias can be potentially fatal and sudden
cardiac death (SCD) is often the first manifestation of these diseases
(8, 9).
Epidemiological data show that in the western adult population, cardiac
canalopathies constitute 1 to 2% of the most frequently diagnosed
predisposing pathologies (10). However,
some studies show that cardiac canalopathies are responsible for
approximately 1/3 of the cases of SCD in young people and for up to 50%
of cases of arrhythmic SCD in this same population
(1, 11).
Genetic cardiac arrhythmias are rare in clinical practice, but can have
a more severe course, especially in children and adolescents
(12). Thus, for the genetic evaluation of
patients, with suspicion of this abnormality, their condition and family
history must be considered (4).
The genetic panels used in this diagnosis can be general or specific,
the first when the individual’s clinical condition does not allow an
accurate identification of the possible mutation related to a particular
gene, the second when the clinical condition allows suspicion of a
particular mutation or when there is a previous examination carried out
on a family member that indicates the presence of a mutation
(6, 11).
Given this, it can be mentioned that the main hereditary arrhythmias in
children and adolescents, caused by dysfunction of the ion channels are
Brugada syndrome (SBr) with an approximate prevalence of 1: 3,300
individuals and the long QT syndrome (LQTS) with prevalence of 1: 2,500
(8, 13).
However, few studies address the physiological effects of these
conditions on children and adolescents.
2. METHODOLOGY
1. Literary review strategies
A literary review was carried out in order to summarize the results
available from the studies found that were related to the theme. To
identify the eligible articles, a search was performed in the literature
of Pubmed, Scielo and Google scholar. The search was limited to articles
written in English in the last 5 years, so articles published between
January 2014 and January 2019 were included. We used the following
descriptors to search: Cardiac voltage-gated sodium channel; mutations;
Cardiac Mutations; Children; and teenagers.
To identify the eligible articles, a search was performed in the
literature of Pubmed, Scielo and Google scholar. The search was limited
to articles written in English in the last 5 years, so articles
published between January 2014 and January 2019 were included. We used
the following descriptors to search: Cardiac voltage-gated sodium
channel; mutations; Cardiac Mutations; Children; and teenagers.
In addition, reference lists were scanned from retrieved studies to
identify any articles that may have been lost in the literature search.
The studies included in this review were selected based on the inclusion
and exclusion criteria shown in Figure 1.
Figure 1: Flow diagram of research strategy and study selection