Intellectual and Neurodevelopmental Delays in Pediatric Catecholaminergic Polymorphic Ventricular Tachycardia: Distinct Characteristics and a More Malignant Neurocardiac Phenotype.

BACKGROUND: Marked intellectual and neurodevelopmental delay (INDD) was noted in 6 unrelated patients diagnosed with RYR2-related catecholaminergic polymorphic ventricular tachycardia (CPVT) from a single center. Patients exhibited similar distinct phenotypic features not previously described. We ai...

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Authors: Miyake CY, Kallas D, Stephens SB, Moore OM, Wehrens XHT, Fischbach PS, LaPage MJ, Landstrom AP, Law IH, Hill AC, Kannankeril PJ, Fish FA, Howard TS, Valdes SO, Pham TD, Kim JJ, Dhillon S, Johnsrude CL, Krause U, Sarquella-Brugada G, Kubus P, Tavacova T, Kwok SY, Etheridge SP, Tisma-Dupanovic S, Kean AC, Krahn AD, Ebrahim M, Atallah J, Fournier A, Batra AS, Young ML, Perry J, Kovach JR, Kamp AN, Clark BC, Jimenez E, Charafeddine F, Hamilton RM, Balaji S, Sanatani S
Format: article
Status:Published version
Publication Date:2025
Country:España
Institution:Fundació Sant Joan de Déu
Repository:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
OAI Identifier:oai:fsjd.fundanetsuite.com:p29169
Online Access:https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=29169
Access Level:Open access
Keyword:arrhythmias, cardiac
phenotype
polymorphic catecholergic ventricular tachycardia
ryanodine receptor calcium release channel
tachycardia, ventricular
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spelling Intellectual and Neurodevelopmental Delays in Pediatric Catecholaminergic Polymorphic Ventricular Tachycardia: Distinct Characteristics and a More Malignant Neurocardiac Phenotype.Miyake CYKallas DStephens SBMoore OMWehrens XHTFischbach PSLaPage MJLandstrom APLaw IHHill ACKannankeril PJFish FAHoward TSValdes SOPham TDKim JJDhillon SJohnsrude CLKrause USarquella-Brugada GKubus PTavacova TKwok SYEtheridge SPTisma-Dupanovic SKean ACKrahn ADEbrahim MAtallah JFournier ABatra ASYoung MLPerry JKovach JRKamp ANClark BCJimenez ECharafeddine FHamilton RMBalaji SSanatani Sarrhythmias, cardiacphenotypepolymorphic catecholergic ventricular tachycardiaryanodine receptor calcium release channeltachycardia, ventricularBACKGROUND: Marked intellectual and neurodevelopmental delay (INDD) was noted in 6 unrelated patients diagnosed with RYR2-related catecholaminergic polymorphic ventricular tachycardia (CPVT) from a single center. Patients exhibited similar distinct phenotypic features not previously described. We aimed to determine the prevalence of INDD in CPVT, compare clinical characteristics between patients with CPVT with and without INDD, and investigate the possibility of a unique neurocardiac CPVT phenotype. METHODS: Retrospective combined review of patients with RYR2-related CPVT diagnosed =18 years with and without INDD from a single center and the International Pediatric CPVT Registry. Patients with hypoxic ischemic insult were excluded unless INDD preceded injury. RESULTS: Among a total of 168 patients, INDD was reported in 19 (11.3% [95% CI, 7.0%-17.1%]). When compared with cases without INDD, patients with INDD exhibited distinct features including (1) younger age at onset of symptoms (median 7.0 versus 10.0 years; P=0.04); (2) higher frequency of atrial tachyarrhythmias (84.2% versus 16.3%, P<0.001); (3) atrial or ventricular tachycardia without adrenergic stimulation (81.3% versus 2.2%, P<0.001, 31.6% versus 4.5%, P=0.001 respectively); (4) cardiac structural changes or systolic dysfunction (36.8% versus 1.3%, P<0.001); and (5) higher incidence of cardiac arrest or sudden death after diagnosis (26.3% versus 2.7%, P=0.001). INDD-related RYR2 genetic variants clustered within the central and channel domains and may be specific to certain variants. CONCLUSIONS: This study demonstrates a wider spectrum of RYR2-related disease, with a subset associated with extracardiac manifestations. Certain RYR2 variants may lead to a neurocardiac phenotype with distinct features that are important to recognize, as these patients may be at higher risk.LIPPINCOTT WILLIAMS & WILKINS2025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=29169Circulation-Arrhythmia and ElectrophysiologyISSN: 19413149ISSNe: 19413084reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déuinstname:Fundació Sant Joan de DéuInglésinfo:eu-repo/semantics/openAccessoai:fsjd.fundanetsuite.com:p291692026-05-27T12:37:41Z
dc.title.none.fl_str_mv Intellectual and Neurodevelopmental Delays in Pediatric Catecholaminergic Polymorphic Ventricular Tachycardia: Distinct Characteristics and a More Malignant Neurocardiac Phenotype.
title Intellectual and Neurodevelopmental Delays in Pediatric Catecholaminergic Polymorphic Ventricular Tachycardia: Distinct Characteristics and a More Malignant Neurocardiac Phenotype.
spellingShingle Intellectual and Neurodevelopmental Delays in Pediatric Catecholaminergic Polymorphic Ventricular Tachycardia: Distinct Characteristics and a More Malignant Neurocardiac Phenotype.
Miyake CY
arrhythmias, cardiac
phenotype
polymorphic catecholergic ventricular tachycardia
ryanodine receptor calcium release channel
tachycardia, ventricular
title_short Intellectual and Neurodevelopmental Delays in Pediatric Catecholaminergic Polymorphic Ventricular Tachycardia: Distinct Characteristics and a More Malignant Neurocardiac Phenotype.
title_full Intellectual and Neurodevelopmental Delays in Pediatric Catecholaminergic Polymorphic Ventricular Tachycardia: Distinct Characteristics and a More Malignant Neurocardiac Phenotype.
title_fullStr Intellectual and Neurodevelopmental Delays in Pediatric Catecholaminergic Polymorphic Ventricular Tachycardia: Distinct Characteristics and a More Malignant Neurocardiac Phenotype.
title_full_unstemmed Intellectual and Neurodevelopmental Delays in Pediatric Catecholaminergic Polymorphic Ventricular Tachycardia: Distinct Characteristics and a More Malignant Neurocardiac Phenotype.
title_sort Intellectual and Neurodevelopmental Delays in Pediatric Catecholaminergic Polymorphic Ventricular Tachycardia: Distinct Characteristics and a More Malignant Neurocardiac Phenotype.
dc.creator.none.fl_str_mv Miyake CY
Kallas D
Stephens SB
Moore OM
Wehrens XHT
Fischbach PS
LaPage MJ
Landstrom AP
Law IH
Hill AC
Kannankeril PJ
Fish FA
Howard TS
Valdes SO
Pham TD
Kim JJ
Dhillon S
Johnsrude CL
Krause U
Sarquella-Brugada G
Kubus P
Tavacova T
Kwok SY
Etheridge SP
Tisma-Dupanovic S
Kean AC
Krahn AD
Ebrahim M
Atallah J
Fournier A
Batra AS
Young ML
Perry J
Kovach JR
Kamp AN
Clark BC
Jimenez E
Charafeddine F
Hamilton RM
Balaji S
Sanatani S
author Miyake CY
author_facet Miyake CY
Kallas D
Stephens SB
Moore OM
Wehrens XHT
Fischbach PS
LaPage MJ
Landstrom AP
Law IH
Hill AC
Kannankeril PJ
Fish FA
Howard TS
Valdes SO
Pham TD
Kim JJ
Dhillon S
Johnsrude CL
Krause U
Sarquella-Brugada G
Kubus P
Tavacova T
Kwok SY
Etheridge SP
Tisma-Dupanovic S
Kean AC
Krahn AD
Ebrahim M
Atallah J
Fournier A
Batra AS
Young ML
Perry J
Kovach JR
Kamp AN
Clark BC
Jimenez E
Charafeddine F
Hamilton RM
Balaji S
Sanatani S
author_role author
author2 Kallas D
Stephens SB
Moore OM
Wehrens XHT
Fischbach PS
LaPage MJ
Landstrom AP
Law IH
Hill AC
Kannankeril PJ
Fish FA
Howard TS
Valdes SO
Pham TD
Kim JJ
Dhillon S
Johnsrude CL
Krause U
Sarquella-Brugada G
Kubus P
Tavacova T
Kwok SY
Etheridge SP
Tisma-Dupanovic S
Kean AC
Krahn AD
Ebrahim M
Atallah J
Fournier A
Batra AS
Young ML
Perry J
Kovach JR
Kamp AN
Clark BC
Jimenez E
Charafeddine F
Hamilton RM
Balaji S
Sanatani S
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv arrhythmias, cardiac
phenotype
polymorphic catecholergic ventricular tachycardia
ryanodine receptor calcium release channel
tachycardia, ventricular
topic arrhythmias, cardiac
phenotype
polymorphic catecholergic ventricular tachycardia
ryanodine receptor calcium release channel
tachycardia, ventricular
description BACKGROUND: Marked intellectual and neurodevelopmental delay (INDD) was noted in 6 unrelated patients diagnosed with RYR2-related catecholaminergic polymorphic ventricular tachycardia (CPVT) from a single center. Patients exhibited similar distinct phenotypic features not previously described. We aimed to determine the prevalence of INDD in CPVT, compare clinical characteristics between patients with CPVT with and without INDD, and investigate the possibility of a unique neurocardiac CPVT phenotype. METHODS: Retrospective combined review of patients with RYR2-related CPVT diagnosed =18 years with and without INDD from a single center and the International Pediatric CPVT Registry. Patients with hypoxic ischemic insult were excluded unless INDD preceded injury. RESULTS: Among a total of 168 patients, INDD was reported in 19 (11.3% [95% CI, 7.0%-17.1%]). When compared with cases without INDD, patients with INDD exhibited distinct features including (1) younger age at onset of symptoms (median 7.0 versus 10.0 years; P=0.04); (2) higher frequency of atrial tachyarrhythmias (84.2% versus 16.3%, P<0.001); (3) atrial or ventricular tachycardia without adrenergic stimulation (81.3% versus 2.2%, P<0.001, 31.6% versus 4.5%, P=0.001 respectively); (4) cardiac structural changes or systolic dysfunction (36.8% versus 1.3%, P<0.001); and (5) higher incidence of cardiac arrest or sudden death after diagnosis (26.3% versus 2.7%, P=0.001). INDD-related RYR2 genetic variants clustered within the central and channel domains and may be specific to certain variants. CONCLUSIONS: This study demonstrates a wider spectrum of RYR2-related disease, with a subset associated with extracardiac manifestations. Certain RYR2 variants may lead to a neurocardiac phenotype with distinct features that are important to recognize, as these patients may be at higher risk.
publishDate 2025
dc.date.none.fl_str_mv 2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=29169
url https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=29169
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv LIPPINCOTT WILLIAMS & WILKINS
publisher.none.fl_str_mv LIPPINCOTT WILLIAMS & WILKINS
dc.source.none.fl_str_mv Circulation-Arrhythmia and Electrophysiology
ISSN: 19413149
ISSNe: 19413084
reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
instname:Fundació Sant Joan de Déu
instname_str Fundació Sant Joan de Déu
reponame_str r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
collection r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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