Suspicion and Persistence: A Case of

Pediatric Brugada Syndrome

Brynn E. Dechert, MSN, CPNP,a Martin J. LaPage, MD, MS,a Mitchell I. Cohen, MDb

This is the case of a 9-year-old girl who initially presents with episodes of abstract
syncope and potentially concerning family history. An extensive evaluation is
unrevealing, and she appears to have simple benign autonomic dysfunction.
Eventually, a rare and life-threatening disease is uncovered, and she receives
appropriate treatment. The case report highlights the persistence and
suspicion of the managing providers that ultimately allowed the diagnosis to
be revealed as well as some of the key features of the underlying disease.

Suspicion is the feeling or thought that
something is possible. Persistence is
the continuance in a course of action
despite difficulty or opposition.
Frequently, the art of medicine requires
the provider to make conclusions with
incomplete information; investigation
into the patient’s ailment must be
based on experience and suspicion. A
diagnosis is not always immediately
clear even with comprehensive testing
and only reveals itself with persistence
and time. In the case to follow, the
patient’s ongoing signs and symptoms
continued to stack evidence against any
serious underlying disease, and it was
only the persistence and suspicion of
the managing providers that ultimately
allowed the diagnosis to be revealed.
CASE REPORT
consults and EEG and head computed
tomography, was unremarkable.
Her father had been evaluated 7 years
before for reported Brugada pattern on
electrocardiogram during fever. He had
also had several syncopal episodes
diagnosed as vasovagal. Evaluation at
that time led to a reported
recommendation for an implantable
cardioverter defibrillator (ICD), but he
declined. The father’s
electrocardiogram result, at the time of
the subject patient’s presentation, was
normal. He was referred to adult
cardiology, which did not suspect
a diagnosis of Brugada syndrome. The
patient’s 4 siblings were asymptomatic
with normal electrocardiogram results.
The patient’s cardiac evaluation
included normal echocardiogram and
Holter monitor results. Her
electrocardiogram result was normal,
a
Department of Pediatrics, University of Michigan, Ann
Arbor, Michigan; and bInova Fairfax Children’s Hospital, Falls
Church, Virginia
Ms Dechert and Dr LaPage cared directly for the
presented patient, drafted the initial case report,
and reviewed and revised the manuscript; Dr Cohen
cared directly for this presented patient and
critically reviewed and revised the article for
intellectual content; and all authors approved the
final manuscript as submitted and agree to be
accountable for all aspects of the work.
DOI: https://doi.org/10.1542/peds.2018-3296
Accepted for publication Jan 11, 2019
Address correspondence to Brynn E. Dechert, MSN,
CPNP, Division of Pediatric Cardiology, Department of
Pediatrics, University of Michigan, 1540 E Hospital Dr,
Ann Arbor, MI 48109. E-mail: brynnd@med.umich.edu
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online,
1098-4275).
Copyright © 2019 by the American Academy of
Pediatrics

including placement of V1 and V2 at FINANCIAL DISCLOSURE: The authors have indicated

The patient presented at age 9 to
a pediatric electrophysiologist (M.I.C.)
after experiencing 4 episodes of
syncope, occurring during various
daily activities but not during exercise
or with fever. Occasionally, these were
associated with palpitations or tonic-
clonic–type movements and an ashen
appearance. Her initial hospital
evaluation, including neurology,
gastroenterology, and infectious disease
a high intercostal space. Procainamide
challenge caused some mild changes in
the V1 and V2 ST segments but was not
diagnostic for Brugada. An implantable
loop recorder (ILR) was implanted to
clarify any future syncope episodes.
Three months later, the family
relocated, and she established care with
another pediatric electrophysiologist
(M.J.L.). Aside from electrocardiogram,
they have no financial relationships relevant to this
article to disclose.
FUNDING: No external funding.
POTENTIAL CONFLICT OF INTEREST: The authors have
indicated they have no potential conflicts of interest
to disclose.
To cite: Dechert BE, LaPage MJ, Cohen MI.
Suspicion and Persistence: A Case of Pediatric
Brugada Syndrome. Pediatrics. 2019;144(1):
e20183296

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PEDIATRICS Volume 144, number 1, July 2019:e20183296 CASE REPORT
FIGURE 1
Wide complex tachycardia recorded by ILR on the day of fever. ECG, electrocardiogram; TS, tachycardia sensed; VS, ventricular sensed beat.

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2 DECHERT et al
FIGURE 2
Baseline, afebrile electrocardiogram showing normal sinus rhythm at 71 beats per minute. A normal appearance of the V1 and V2 precordial leads with
upright T waves in V2 is shown.
no testing was repeated at that time.
Over the following year, she
continued to have frequent, weekly
symptoms, including episodes of
dizziness, chest pain, and near
syncope; hundreds of ILR recordings
showed sinus rhythm. At the annual
follow-up, the family inquired about
removing the ILR. The provider
recommended leaving the ILR in
place because of the low risk and
potential benefit of ongoing
monitoring.
Serendipitously, 5 months later
(20 months after ILR implant),
a sustained wide complex arrhythmia
was documented by her ILR (Fig 1)
during a febrile illness. At the time of
arrhythmia, she was transiently
lightheaded but not syncopal. Full
evaluation was repeated, including
echocardiogram and exercise tests,
which had normal results.
Electrocardiogram obtained after the
fever resolved did not show
a diagnostic Brugada pattern. Genetic
testing was sent. Procainamide
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PEDIATRICS Volume 144, number 1, July 2019
challenge was repeated, resulting in
T-wave inversion in V1 and V2 but
insufficient ST elevation to qualify as
a positive test result. A ventricular
stimulation study without
isoproterenol using single and double
premature ventricular extrastimuli
from the apex resulted in occasional
couplets and triplets of ventricular
ectopy. A more aggressive approach
using S4 premature ventricular
extrastimuli induced monomorphic
ventricular tachycardia, which
progressed abruptly to polymorphic
ventricular tachycardia and
ventricular fibrillation necessitating
defibrillation. These findings, in light
of the previous history, were
discussed with the family as well as
several colleagues who varied widely
in their opinions on whether to
implant an ICD. It was decided to
implant a subcutaneous implantable
cardioverter defibrillator (S-ICD).
Just 2 days before her scheduled
S-ICD implantation, the patient
became febrile. She was immediately
treated with antipyretics and
instructed to present to the clinic to
attempt to obtain an
electrocardiogram during fever. The
result from afebrile
electrocardiogram on arrival was
normal (Fig 2). Six hours later, she
remanifested a temperature of 39.3ºC
while in the clinic. Electrocardiogram
then performed with high V1-V2 lead
placement was diagnostic of the
Brugada sign (Fig 3). She was
promptly treated with ibuprofen and
admitted for observation.
She underwent successful
implantation of a S-ICD 2 days later.
Her genetic test eventually returned
with a positive result for a pathologic
mutation in SCN5A (c.384011G.A)
as well as a variant of unknown
significance identified in PKP2
(c.974C.T) also potentially affiliated
with Brugada syndrome. The genetic
testing facility reported the SCN5A
mutation to be likely pathogenic,
having been previously reported
multiple times in association with
3
FIGURE 3
Febrile electrocardiogram with high V1 and V2 placement in the second intercostal space. There is ST elevation $2 mm in V2 with a rectilinear downslope
to baseline followed by an inverted T-wave consistent with the Brugada sign.
Brugada syndrome and absent in
large population cohorts. Familial
cascade screening revealed only
1 genotype-positive sibling who
harbored both mutations. The SCN5A
mutation was inherited from the
father, and the variation of uncertain
significance in PKP2 was inherited
from the mother.
DISCUSSION
Brugada syndrome is a rare,
autosomal-dominant, inherited
channelopathy that predisposes
patients to ventricular arrhythmias
and sudden cardiac death.1,2 The
hallmark of the disease is a specific
pattern of ST segment elevation in the
precordial leads (V1–V3). The
Brugada pattern may be
intermittently present and only
revealed during fever, which also
increases the likelihood of lethal
arrhythmias.3–6 It is therefore
recommended that patients with
known or suspected Brugada
syndrome aggressively treat fever
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4 DECHERT et al
with antipyretic therapy. This case
report highlights the impact of fever
inducing both ventricular
arrhythmias and the Brugada sign,
identifies differing management
approaches among pediatric
electrophysiologists, and illustrates
the role of suspicion and persistence,
which may be critical to accurate
diagnosis.
The majority of presenting and early
evidence in this case did not support
the ultimate diagnosis. Brugada
syndrome typically presents in adult
men, is more often seen in those of
Asian descent, and rarely manifests in
children. The diagnosis can be
difficult because of the inconsistent
presence of the Brugada sign on
baseline electrocardiogram.3–7 The
procainamide challenge may not be
reliable in pediatric patients, as
shown by a large study on
asymptomatic children evaluated
because of family history in which
23% of patients had a negative drug
challenge result before puberty that
eventually became positive after
puberty, indicating that Brugada can
become unmasked with age.8 The
difficulty in diagnosis is important to
overcome because Brugada is thought
to be the cause of sudden cardiac
death in 4% to 12% of children and
young athletes.9
The patient’s frequent symptoms
were repeatedly correlated with
benign rhythms, and the suspected
diagnosis appeared more unlikely
with each passing month. Although
there had been initial suspicion of her
father having a Brugada pattern
during a fever, the diagnosis of
Brugada pattern had never been
confirmed, and subsequent
evaluations had been unremarkable.
Brugada syndrome in a 10-year-old
with documented ventricular
arrhythmias would be a class 1
indication for an ICD implantation. In
this case, however, a definitive
diagnosis of Brugada syndrome had
not yet been established, and
mildly symptomatic, well-tolerated,
self-terminating ventricular
tachycardia would not be an
appropriate indication for an
ICD. Repeat testing, including
procainamide challenge, was again
unrevealing in clarifying a diagnosis,
and induced polymorphic ventricular
tachycardia at electrophysiology
study was not specifically
diagnostic. Additionally, there are
significant complication risks of
ICDs in children, including the high
rate of inappropriate shocks.
Before a clear diagnosis of Brugada
being established by
electrocardiogram findings or genetic
testing, the provider (M.J.L.) had
decided to implant an ICD in this
patient. This decision came to be
after extensive discussion with the
patient and her family as well as
with multiple colleagues. The case
was discussed with 4 additional
pediatric electrophysiologists, 2 of
whom stated they would implant an
ICD and 2 whom stated they would
not in this case. These opinions
were openly shared with the family,
who ultimately agreed with S-ICD
implantation, which is
recommended to mitigate the long-
term complications of
a transvenous system. The diagnosis
was ultimately confirmed by the
febrile electrocardiogram findings
and shortly thereafter by the
genetic testing results. The case is
illustrative of the wide variation in
treatment strategies for nonspecific
diagnostic findings even a life-
threatening disease is potentially
present.
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PEDIATRICS Volume 144, number 1, July 2019
CONCLUSIONS
The diagnosis of Brugada syndrome,
or any rare disease, in children may
be difficult. Pediatric diseases can
evolve over time. Suspicion and
persistence are important qualities
for a provider to apply judiciously
and may even be critically important
in life-threatening diseases, such as
Brugada syndrome. The early
markers of Brugada syndrome in
pediatric patients and the best
treatments are yet to be discovered,
and future effort should be directed
at developing pediatric
electrocardiogram standards as well
as management recommendations for
pediatric patients.
ABBREVIATIONS
ICD: implantable cardioverter
defibrillator
ILR: implantable loop recorder
S-ICD: subcutaneous implantable
cardioverter defibrillator
REFERENCES
1. Brugada P, Brugada J. Right bundle
branch block, persistent ST segment
elevation and sudden cardiac death:
a distinct clinical and
electrocardiographic syndrome. A
multicenter report. J Am Coll Cardiol.
1992;20(6):1391–1396
2. Priori SG, Wilde AA, Horie M, et al. HRS/
EHRA/APHRS expert consensus
statement on the diagnosis and
management of patients with inherited
primary arrhythmia syndromes:
document endorsed by HRS, EHRA, and
APHRS in May 2013 and by ACCF, AHA,
PACES, and AEPC in June 2013. Heart
Rhythm. 2013;10(12):1932–1963
3. Bayés de Luna A, Brugada J, Baranchuk
A, et al. Current electrocardiographic
criteria for diagnosis of Brugada
pattern: a consensus report [published
correction appears in J Electrocardiol.
2013;46(1):76]. J Electrocardiol. 2012;
45(5):433–442
4. Dumaine R, Towbin JA, Brugada P, et al.
Ionic mechanisms responsible for the
electrocardiographic phenotype of the
Brugada syndrome are temperature
dependent. Circ Res. 1999;85(9):
803–809
5. Porres JM, Brugada J, Urbistondo V,
García F, Reviejo K, Marco P. Fever
unmasking the Brugada syndrome.
Pacing Clin Electrophysiol. 2002;25(11):
1646–1648
6. Kum LC, Fung JW, Sanderson JE.
Brugada syndrome unmasked by
febrile illness. Pacing Clin
Electrophysiol. 2002;25(11):1660–1661
7. Probst V, Denjoy I, Meregalli PG, et al.
Clinical aspects and prognosis of
Brugada syndrome in children.
Circulation. 2007;115(15):2042–2048
8. Conte G, de Asmundis C, Ciconte G, et al.
Follow-up from childhood to adulthood
of individuals with family history of
Brugada syndrome and normal
electrocardiograms. JAMA. 2014;
312(19):2039–2041
9. Sarquella-Brugada G, Campuzano O,
Iglesias A, et al. Genetics of sudden
cardiac death in children and young
athletes. Cardiol Young. 2013;23(2):
159–173
5
 Suspicion and Persistence: A Case of Pediatric Brugada Syndrome
Brynn E. Dechert, Martin J. LaPage and Mitchell I. Cohen
Pediatrics 2019;144;
DOI: 10.1542/peds.2018-3296 originally published online June 12, 2019;

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 Suspicion and Persistence: A Case of Pediatric Brugada Syndrome
Brynn E. Dechert, Martin J. LaPage and Mitchell I. Cohen
Pediatrics 2019;144;
DOI: 10.1542/peds.2018-3296 originally published online June 12, 2019;

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://pediatrics.aappublications.org/content/144/1/e20183296

Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it
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the American Academy of Pediatrics, 345 Park Avenue, Itasca, Illinois, 60143. Copyright © 2019
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