Journal of Pediatric Cardiology and Cardiac Surgery 8(2): 53‒59 (2024)

Review[JSPCCS 59th Annual Conference]

Pathogenic Variants Associated with Cardiomyopathy
in Pediatric Myocarditis as Outcome Predictors
Franziska Seidel, MD1, 2, 3, 4), Nele Rolfs, MD1, 2, 4), Tobias Hecht, MD5),
Johanna Hummel, MD5), Hendrik Milting, MSc, PhD6),
Daniel Messroghli, MD, PhD2, 4, 7), and Stephan Schubert, MD, PhD5)
1) Deutsches Herzzentrum der Charité, Department of Congenital Heart Disease‒Pediatric Cardiology,

Berlin, Germany

2) Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlinand Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany3) Experimental & Clinical Research Center, a cooperation between the Max-Delbrück-Center for Molecular Medicine

in the Helmholtz Association & Charité-Universitätsmedizin Berlin, Germany

4) DZHK (German Centre for Cardiovascular Research), partner site Berlin, Germany5) Center for Congenital Heart Disease/Pediatric Cardiology, Heart and Diabetes Center NRW, University Hospitalof the Ruhr University Bochum, Medical Faculty OWL (University of Bielefeld), Germany6) Erich & Hanna Klessmann-Institute, Heart and Diabetescenter NRW, University
Clinic of Ruhr University Bochum, Bad Oeynhausen, Germany7) Deutsches Herzzentrum der Charité, Department of Cardiology, Angiology
and Intensive Care Medicine, Berlin, Germany

Myocarditis in children and adolescents has different courses. Infants and young children suffer more frequently
from severe heart failure. In adolescence, on the other hand, patients are more likely to present with chest pain
and preserved cardiac function. At the same time, the recovery rate is significantly higher. The influence of disease-associated genetic variants in myocarditis is now widely recognized. Such variants are more common inyounger children and in patients with severe heart failure and a phenotype of dilated cardiomyopathy. However,genetic changes have also been described in children with myocarditis and preserved cardiac function, particularly in desmosomal genes. These genetic variants are associated with an increased number of cardiovascular
events. This review aims to provide an overview of the impact of genetic variants on the clinical presentation andoutcome of pediatric myocarditis.

Keywords: myocarditis, pediatric, genetic variants, cardiomyopathy, outcome

Introduction
Myocarditis is a disease with many different appearances. It can pass unnoticed or have a mild course oreven lead to a serious course with severely impaired
cardiac function and heart failure.1) In children, particularly severe courses occur in infants and young children.

Adolescents tend to have milder courses of the disease,which has led to the hypothesis of different pathomechanism in the different age groups.2) In addition to agerelated differences in immunological response, genetic
variants in cardiomyopathy genes are currently being
discussed.3, 4) These could be a cause of severe heart failure with impaired function and the phenotype of dilated

J-STAGE Advance Published Online: July 4, 2024
Corresponding author: Stephan Schubert, MD, PhD, Center for Congenital Heart Disease/Pediatric Cardiology, Heart and Diabetes
Center NRW, University Hospital of the Ruhr University Bochum, Medical Faculty OWL (University of Bielefeld), University Clinic of
Ruhr-University Bochum Georgstr. 11, 32545 Bad Oeynhausen, Germany
E-mail: sschubert@hdz-nrw.de
Stephan Schubert ( https://orcid.org/0000-0003-2894-6490)
doi: 10.24509/jpccs.23-020© 2024 Japanese Society of Pediatric Cardiology and Cardiac Surgery
This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/)

54

cardiomyopathy (DCM) in children with myocarditis.
However, it is unclear whether these children alreadyhad a DCM phenotype prior to the initial presentation
and whether an additional infection led to a further
deterioration of the condition. Another hypothesis isthat the clinical picture of the DCM phenotype only
becomes apparent after an infection. The presence ofgenetic variants in cardiomyopathy genes, however, may
then lead to the severe phenotype.5, 6) Little is known
about the outcome of children and adolescents withmyocarditis in the presence of genetic variants in cardiomyopathy genes. The aim of this review is to provide
an overview of the presence of these genetic variants
in pediatric myocarditis and their impact on clinicalpresentation and phenotypes. Whereas myocarditis isdefined according to the available histologic, immunologic and immunhistochemic criteria.7) In addition, theimpact of the genetic predisposition on the outcome ofthe disease is highlighted. These findings could improverisk prediction and may influence subsequent therapy
management in the context of listing for heart transplantation or weaning from mechanical circulatory
support systems. The prospective multicenter registry
for children and adolescents with suspected myocarditis“MYKKE” aims to investigate pediatric myocarditis andits course as well as to identify different pathomecha-

nisms. Previously published data on genetic findings of
myocarditis patients within the “MYKKE” registry serveas the basis for this review.2, 3, 8)

Heterogeneous Clinical Presentationof Pediatric Myocarditis
As mentioned above, pediatric myocarditis manifests
with varying symptoms and ranges from severe heart
failure to a mild disease course with rapid resolutionof symptoms. The often non-specific symptoms andtheir diversity frequently cause a delay in diagnosis.9)
The age distribution of pediatric myocarditis reveals
two distinct peaks: infancy and adolescence.10, 11) This isaccompanied by differences in the clinical presentation.
In the multicenter registry “MYKKE”, patients<2 yearsof age were more likely to have severe left-ventricular
impairment and cardiac adverse events like need formechanical circulatory support and death, with an evensex distribution in this age group (Figs. 1 and 2). This
cohort presents with a heart failure-like myocarditis.
The probability of severe disease progression declines
with age by 14% a year.2, 3, 12) Nearly half of the children
with impaired function at initial presentation do notrecover fully.13) Another large multicenter study foundthat moderate to severe ventricular dysfunction was
associated with young age, female sex and the presence

Fig. 1 Transthoracic echocardiography in chronic lymphocytic myocarditis with the phenotype of dilated cardiomyopathy and acute heart failure
A. Transthoracic echocardiography with 4 chamber view in a 1 month old child with myocarditis and phenotype of dilative
cardiomyopathy (Left ventricular (LV) ejection fraction 38%, LV diameter 26 mm (Z-Score +3,5); B. short axis view. The
endomyocardial biopsy revealed a virus negative chronic lymphocytic myocarditis. Genetic panel diagnostic reveals nopathological result, but WES was currently not performed. LA, left atrium; LV, left ventricular; RA, right atrium; RV, rightventricular

J Pediatr Cardiol Card Surg Vol. 8, No. 2 (2024)

55

Fig. 2 X-ray in a child (1 month) with chronic lymphatic myocarditis with the phenotype of dilated cardiomyopathy
and acute heart failure
A. X-ray with enlarged heart and with pulmonic congestion prior (acute heart failure) and B. post implantation of a left ventricular assist device (LVAD, Berlin Heart EXCOR® 10cc) with reduced heart size and congestion. The endomyocardial biopsy
revealed a virus negative chronic lymphocytic myocarditis. This is showing the acute therapeutic eﬀect of VAD therapy inorder to complete diagnostic workup.

of respiratory distress and gastrointestinal symptoms(including nausea, emesis, diarrhea, poor appetite).10)
The presence of unspecific gastrointestinal symptoms
such as emesis and abdominal pain may delay diagnosisof myocarditis in younger children.14) A Japanese survey
study found that in pediatric patients with acute andfulminant myocarditis, gastrointestinal symptoms wereeven more common than cardiorespiratory symptoms at
the onset of the disease.15)
In contrast to that, myocarditis in adolescentʼs manifests most often with chest pain or acute coronary
syndrome-like symptoms. Chest pain was the mostcommon symptom in adolescent patients with preservedor mildly reduced ventricular function.10, 16) Among theadolescents diagnosed with myocarditis, males accountfor about two-thirds of patients.2) This is consistent withfindings of myocarditis in adults, which thus might sharesimilar pathophysiologic mechanisms.17‒19)
In the sub-study of the “MYKKE” registry, patientswith myocarditis and DCM phenotype with 35%
disease-associated genes had a significantly worse
event-free survival compared to the group without DCM
phenotype, but also compared to a group of children
with DCM and no evidence of inflammation. In addition to the genetic background, myocardial inflammation appeared to be an important factor influencing theoutcome.3)

Genetic Predisposition in Pediatric Myocarditis
It has been shown that there is an influence of genetic
variants in the context of myocarditis.1) The proportionof myocarditis patients with pathogenic variants ranges
from 8 to 16% in larger adult cohorts.20, 21) However, thenumber of pathogenic variants detected increases significantly to 33% with the severity of the myocarditis.22)
These are particularly cardiomyopathy-associated genesthat affect the sarcomere and desmosome. In addition
to the phenotype of DCM, arrhythmogenic right ventricular cardiomyopathy (ARVC) with the occurrence ofmalignant cardiac arrhythmias also plays a major role inmyocarditis, with ARVC being more frequently associated with variants in desmosomal genes.23‒25)
The number of cases for genetic variants in children and adolescents with myocarditis is limited(Table 1). Small cohorts show varying frequencies, but
again depending on the severity of the disease. Amonga cohort of eight children, all of whom were treated for
acute heart failure or cardiac arrest at a pediatric intensive care unit, likely pathogenic or pathogenic variants
were found in seven of these children. Half of thesechildren were under one year of age. The identified cardiomyopathy-associated variants included titin (TTN,n=2); myosin binding protein C3 (MYBPC3, n=1);
Troponin T2 (TNNT2, n=1) and sodium voltage-gatedchannel alpha subunit 5 (SCN5A, n=1). Two patients© 2024 Japanese Society of Pediatric Cardiology and Cardiac Surgery

56

Cardiac arrhythmia like ventricular tachycardia (VT)was reported in one patient. This group of patients can
be clinically classified as having chest pain-like myocarditis, not only due to the described symptoms, but also
based on the patientsʼ ages of 10‒17 years. In addition,
recurrent myocarditis, a positive family history for
myocarditis and distinctive patterns in late enhancement sequences on magnetic resonance imaging withseptal enhancement and a ring-like pattern as well as
non-sustained VT were found more frequently in theentire presented cohort with pathogenic desmosomal
gene variants compared to patients without desmosomal
gene variants.24) A sub-study of the “MYKKE” registry
examined 42 patients with biopsy-confirmed myocarditis by targeted panel sequencing for cardiomyopathyassociated genes. Likely pathogenic and pathogenic

had genetically confirmed underlying syndromic diseases (Alström and Hurler syndrome).26) In contrast,
in another cohort of seven children with genetic testing
and an initial diagnosis of myocarditis, only one single
pathogenic variant was found in the Lamin A (LMNA)
gene.27) Further, genetic variants in three out of 13 children (23%) with acute myocarditis are reported, withtwo cases exhibiting multiallelic variants.21)
In contrast, Ammirati et al. reported 10 children withacute myocarditis and genetic variants in desmosomal
genes (desmoplakin (DSP) n=8; plakophilin 2 (PKP2)
and desmoglein 2 (DSG2), n=1 respectively), with
only one child having a reduced left ventricular ejection
fraction (LVEF) of 43%, the others had a preserved
LVEF. All had chest pain; four also had palpitations, one
a syncope and one presented with additional dyspnea.

Table 1 Genetic characterization of pediatric patients with myocarditis
Patient
characteristics(age, sex)

Authors

Year ofpublication

Brown EE et al.26)

201950%<1 y (range 3
weeks to 14 y)
88% female

8

Kontorovich AR
et al.21)

2021

Age<20 y

13* Pt 1 (13 y, female):multiallelic TTN
Pt 2 (0.6 y, female):
PRDM, DSP, DNM2,DMD (multiallelic)Pt 3 (19 y, female): DSP

Seidel F et al.3)

2017

MYC-DCM (n=20):
median age 1.4 y;
55% male
MYC-NonDCM(n=22):
median age 16 y;
64% male

42

Ammirati E
et al.24)

2022

Median age 15.5 y;
90% male (n=9)

10* DSP n=8
DSG2 n=1
PKP2 n=1

Chest pain, palpitations, Acute myocarditis withelevated serum troevidence in biopsy
ponins, preserved LVEF
and/or cardiac MRI

van der Meulen
MH et al.27)

2022

Age<18 y, nofurther details
available

7* LMNA n=1

Acute heart failure with
reduced LVEF, LV
dilatation

Samplesize

Genotype

Cardiac phenotype

Myocarditis type

TTN n=2;
TNNT2 n=1;
MYBPC3 n=1;
SCN5A n=1;
Syndromic disease n=2(Alström & Hurler
syndrome)

Acute heart failure with
reduced LVEF, LV
dilatation

Suspected myocarditis attime of presentation

No in depthcharacterization

Acute myocarditis withhistological evidence

22% with LP/P variants:
MYC-DCM: Acute heart
Myocarditis with
MYC-DCM (35%, n=7):
failure with reduced
histological evidence
BAG3 n=2
LVEF (median 22%), LV(acute or chronic/
LMNA n=1
dilatation
healing)
MYH7 n=1
MYC-NonDCM: chest
TNNI3 n=1
pain, arrhythmias, preTNNT2 n=1
served LVEF (median
TTN n=1
59%)
MYC-NonDCM (9%, n=2):
DSP n=2

Deﬁnite or probablemyocarditis

BAG3, BAG cochaperone 3; DMD, duchenne muscular dystrophy; DNM2, dynamin 2; DSG2, desmoglein 2; DSP, desmoplakin; LMNA, lamin
A; LV, left ventricular; LVEF, LV ejection fraction; MRI, magnetic resonance imaging; MYBPC3, myosin binding protein C3; MYH7, myosin
heavy chain 7; PKP2, plakophilin 2; RYR2, ryanodine receptor 2; SCN5A, sodium voltage-gated channel alpha subunit 5; TNNC1, troponin C1;
TNNI3, troponin I3; TNNT2, Troponin T2; TTN, titin. * Sample size indicated represents only a sub-cohort in the study, therefore some detailed
information on age or sex may not be available.

J Pediatr Cardiol Card Surg Vol. 8, No. 2 (2024)

57

Fig. 3 Relationship of clinical and genetic ﬁndings inpediatric myocarditis
Pathogenic genetic variants were found in all entities of pediatric myocarditis. Children with heart
failure-like myocarditis tended to be younger andare more likely to have disease-associated variants
in sarcomere genes, while in adolescents with chest
pain-like myocarditis desmosomal gene variants
have been identiﬁed.

genes were found in nine children (22%). However,they were significantly more frequent in children with
the DCM phenotype (MYC-DCM, n=20), who again
belonged to the heart failure-like myocarditis groupwith a median age of 1.4 years. They were compared
to a group without DCM phenotype (MYC-NonDCM,n=22) with a median age of 16.1 years. In contrast, thelatter group presented with chest pain and ST-segment
elevation on electrocardiogram, which once again places
them in the chest pain-like myocarditis cohort. Overall,disease-associated variants were identified in seven out
of 20 children in the MYC-DCM cohort (35%). These
were variants in the genes BAG cochaperone 3 BAG3(n=2), LMNA, myosin heavy chain 7 (MYH7), troponin
I3 (TNNI3), TNNT2 and TTN (n=1, respectively). In
two of the patients from the MYC-NonDCM cohort,however, DSP was identified as the disease-associatedvariant.3)
In a second study, in addition to cardiomyopathyassociated genes, immune disorder genes were examined in 12 children with severe courses of myocarditis
and their families. Cardiomyopathy-associated variants
were found in the majority (8/12 patients, 67%) of thesechildren. Looking at the immune disorder genes, likely
pathogenic variants were also found in three patients(dynein axonemal heavy chain 11 (DNAH11), FA complementation group C (FANCC), and sperm-associatedantigen 1 (SPAG1)). Overall, variants in genes associated with ciliary transport were frequently present.

Fig. 4 Overview of gene distribution in pediatricmyocarditis
Variants in sarcomer genes were detected in 46%(n=15) of pediatric myocarditis patients, compared
to desmosomal genes in 36% (n=12) and others in
18% (n=6).3, 8, 21, 24, 26, 27) BAG3, BAG cochaperone
3; DSG2, desmoglein 2; DSP, desmoplakin; LMNA,
lamin A; MYBPC3, myosin binding protein C3; MYH7,
myosin heavy chain 7; PKP2, plakophilin 2; RYR2,
ryanodine receptor 2; SCN5A, sodium voltage-gatedchannel alpha subunit 5; TNNC1, troponin C1;
TNNI3, troponin I3; TNNT2, Troponin T2; TTN, titin.

The impact of this on the progression of myocarditis is
unclear and requires further exploration.8)
In summary, these results highlight clear clinical andgenetic differences in children and adolescents withcardiomyopathy-associated genetic variants and myocarditis (Fig. 3). Overall, infants or young children withheart failure-like myocarditis are more likely to havealterations in sarcomere genes, whereas adolescentswith chest pain-like myocarditis and preserved cardiac
function are more likely to have genetic variants in desmosomal genes (Fig. 4).

Outcome of Patients with PediatricMyocarditis and Genetic BackgroundA remarkable number of pediatric patients withmyocarditis requires heart transplantation (17‒19%)
and the overall mortality in pediatric myocarditis lies
around 6%.28) As mentioned earlier, data show that there© 2024 Japanese Society of Pediatric Cardiology and Cardiac Surgery

58

is an accumulation of genetic variants in severe disease
courses.3)
In a pediatric DCM cohort, younger children withlikely pathogenic or pathogenic variants were significantly more likely to undergo heart transplantation or
decease.27) However, in a mixed cohort of children andadults, no significant difference in clinical outcome
was found between patients with and without detected
genetic variants. The two children mentioned there withmultiallelic genetic cardiomyopathy-associated variants
and myocarditis underwent left ventricular assist device
implantation and heart transplantation.21)
A similar outcome was found in the eight patientsfrom the Brown et al. cohort. Those with evidence ofgenetic variants did not show recovery, instead twochildren died and five other children needed heart transplantation or were listed for transplantation.26)
With regard to desmosomal genes in acute myocarditis and preserved myocardial function of the chest
pain-like type myocarditis, it is shown that the incidence
of death, heart failure, ventricular tachycardia and myocarditis recurrence is significantly increased in patientswith detected variants in desmosomal genes comparedto patients without variant detection and to patients
without genetic testing at all.24)

Conclusion
Especially in children with severe courses of myocarditis, there is an accumulation of genetic variants in cardiomyopathy-associated genes. This particularly affects
infants and young children and children with impaired
cardiac function. These conditions can be described asheart failure-like myocarditis. The genes identified relate
in particular to sarcomere genes. In contrast, adolescentswith preserved function and acute myocarditis tend tohave pathogenic variants in desmosomal genes, which
also exhibited more cardiovascular events. Thus, clinicalpresentation suggests genetic variants in pediatric myocarditis that may affect clinical decision and outcome
and underscores the importance of genetic testing inpediatric myocarditis.
Acknowledgments
Genetic data from the MYKKE registry were interpreted by the AG Klaassen at the Experimental andClinical Research Center, A Cooperation between the
Max-Delbrück-Center for Molecular Medicine in the
J Pediatr Cardiol Card Surg Vol. 8, No. 2 (2024)

Helmholtz Association and the Charité-Universitätsmedizin Berlin. Special thank here to Sabine Klaassen, Jirko
Kühnisch and Josephine Dartsch.
We thank the National Register for Congenital Heart
Defects, Germany for support of the infrastructure of
MYKKE and the Biobank ZeBANC at Charité for sample
preparation.
Funding
Since 2017 the MYKKE registry is supported by kinderherzen-Fördergemeinschaft Deutsche Kinderherzzentren
e.V. (Bonn, Germany). Parts of the registry were funded
by a research grant from the Berliner Sparkassen Stiftung
Medizin since 2019. Logistic support and managementof the research database are provided by the Competence
Network for Congenital Heart Defects (Berlin, Germany)and the National Registry for Congenital Heart Defects(Berlin, Germany), which both received funding from theFederal Ministry of Education and Research, grant number
01GI0601 and 01KX2140.
Conﬂicts of Interest
The authors have nothing to disclose in relation to thisproject.
Author Contribution
Conceptualization, F.S., H.M. and S.S.; methodology,
F.S., D.M., H.M. and S.S.; formal analysis, F.S., and N.R.;
investigation, F.S., N.R., T.H., J.H., H.M. and S.S.; resources,
F.S., N.R., T.H, J.H., H.M., D.M. and S.S.; writing̶originaldraft preparation, F.S., N.R. and S.S.; writing̶review and
T.H., J.H., H.M. and D.M.; funding acquisition, F.S., H.M.,
D.M. and S.S.

References
1) Basso C: Myocarditis. N Engl J Med 2022; 387: 1488‒1500
2) Messroghli DR, Pickardt T, Fischer M, et al: MYKKE Consortium: Toward evidence-based diagnosis of myocarditis
in children and adolescents: Rationale, design, and firstbaseline data of MYKKE, a multicenter registry and study
platform. Am Heart J 2017; 187: 133‒1443) Seidel F, Holtgrewe M, Al-Wakeel-Marquard N, et al:
Pathogenic variants associated with dilated cardiomyopathy predict outcome in pediatric myocarditis. Circ Genom
Precis Med 2021; 14: e003250
4) Arbelo E, Protonotarios A, Gimeno JR, et al: ESC Scientific Document Group: 2023 ESC Guidelines for the
management of cardiomyopathies. Eur Heart J 2023; 44:3503‒3626

595) Belkaya S, Kontorovich AR, Byun M, et al: Autosomal
recessive cardiomyopathy presenting as acute myocarditis.
J Am Coll Cardiol 2017; 69: 1653‒1665
6) Campuzano O, Fernandez-Falgueras A, Sarquella-Brugada G, et al: A genetically vulnerable myocardium may
predispose to myocarditis. J Am Coll Cardiol 2015; 66:
2913‒2914
7) Caforio AL, Pankuweit S, Arbustini E, et al: European
Society of Cardiology Working Group on Myocardial and
Pericardial Diseases: Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis:
A position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial
Diseases. Eur Heart J 2013; 34: 2636‒2648, 2648a‒2648d
8) Seidel F, Laser KT, Klingel K, et al: Pathogenic variants in
cardiomyopathy disorder genes underlie pediatric myocarditis-further impact of heterozygous immune disorder
gene variants? J Cardiovasc Dev Dis 2022; 9: 216
9) Durani Y, Egan M, Baffa J, et al: Pediatric myocarditis:
Presenting clinical characteristics. Am J Emerg Med 2009;
27: 942‒947
10) Butts RJ, Boyle GJ, Deshpande SR, et al: Characteristics
of clinically diagnosed pediatric myocarditis in a contemporary multi-center cohort. Pediatr Cardiol 2017; 38:1175‒1182
11) Ghelani SJ, Spaeder MC, Pastor W, et al: Demographics,
trends, and outcomes in pediatric acute myocarditis in the
United States, 2006 to 2011. Circ Cardiovasc Qual Outcomes 2012; 5: 622‒62712) Schubert S, Opgen-Rhein B, Boehne M, et al: MYKKE
consortium: Severe heart failure and the need for mechanical circulatory support and heart transplantation in pediatric patients with myocarditis: Results from the prospective multicenter registry “MYKKE”. Pediatr Transplant
2019; 23: e13548
13) Foerster SR, Canter CE, Cinar A, et al: Ventricular remodeling and survival are more favorable for myocarditis thanfor idiopathic dilated cardiomyopathy in childhood: An
outcomes study from the Pediatric Cardiomyopathy Registry. Circ Heart Fail 2010; 3: 689‒69714) Chang YJ, Chao HC, Hsia SH, et al: Myocarditis presenting as gastritis in children. Pediatr Emerg Care 2006; 22:439‒440
15) Saji T, Matsuura H, Hasegawa K, et al: Comparison of theclinical presentation, treatment, and outcome of fulminant and acute myocarditis in children. Circ J 2012; 76:1222‒1228
16) Rodriguez-Gonzalez M, Sanchez-Codez MI, Lubian-Gutierrez M, et al: Clinical presentation and early predictors

17)

18)
19)
20)
21)
22)

23)

24)
25)

26)

27)

28)

for poor outcomes in pediatric myocarditis: A retrospective study. World J Clin Cases 2019; 7: 548‒561
Ammirati E, Frigerio M, Adler ED, et al: Management of
acute myocarditis and chronic inflammatory cardiomyopathy: An expert consensus document. Circ Heart Fail
2020; 13: e007405
Abe T, Tsuda E, Miyazaki A, et al: Clinical characteristics
and long-term outcome of acute myocarditis in children.
Heart Vessels 2013; 28: 632‒638
Miyake CY, Teele SA, Chen L, et al: In-hospital arrhythmia development and outcomes in pediatric patients withacute myocarditis. Am J Cardiol 2014; 113: 535‒540
Lota AS, Hazebroek MR, Theotokis P, et al: Genetic architecture of acute myocarditis and the overlap with inherited
cardiomyopathy. Circulation 2022; 146: 1123‒1134
Kontorovich AR, Patel N, Moscati A, et al: Myopathic cardiac genotypes increase risk for myocarditis. JACC BasicTransl Sci 2021; 6: 584‒592
Tiron C, Campuzano O, Fernandez-Falgueras A, et al:
Prevalence of pathogenic variants in cardiomyopathy-associated genes in myocarditis. Circ Genom Precis Med
2022; 15: e003408
Ader F, Surget E, Charron P, et al: Inherited cardiomyopathies revealed by clinically suspected myocarditis: Highlights from genetic testing. Circ Genom Precis Med 2020;
13: e002744
Ammirati E, Raimondi F, Piriou N, et al: Acute myocarditis associated with desmosomal gene variants. JACC Heart
Fail 2022; 10: 714‒727
Poller W, Haas J, Klingel K, et al: Familial recurrent myocarditis triggered by exercise in patients with a truncating
variant of the desmoplakin gene. J Am Heart Assoc 2020;
9: e015289
Brown EE, McMilllan KN, Halushka MK, et al: Genetic
aetiologies should be considered in paediatric cases ofacute heart failure presumed to be myocarditis. Cardiol
Young 2019; 29: 917‒921
van der Meulen MH, Herkert JC, den Boer SL, et al:
Genetic evaluation of a nation-wide Dutch Pediatric DCM
Cohort: The use of genetic testing in risk stratification.
Circ Genom Precis Med 2022; 15: e002981
Law YM, Lal AK, Chen S, et al: American Heart Association Pediatric Heart Failure and Transplantation Committee of the Council on Lifelong Congenital Heart Disease
and Heart Health in the Young and Stroke Council: Diagnosis and management of myocarditis in children: A Scientific Statement from the American Heart Association.
Circulation 2021; 144: e123‒e135© 2024 Japanese Society of Pediatric Cardiology and Cardiac Surgery