Cardiac phenotype in ATP1A3-related syndromes: A multicenter cohort study.
Détails
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_C9EB42E436AF
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Cardiac phenotype in ATP1A3-related syndromes: A multicenter cohort study.
Périodique
Neurology
ISSN
1526-632X (Electronic)
ISSN-L
0028-3878
Statut éditorial
Publié
Date de publication
24/11/2020
Peer-reviewed
Oui
Volume
95
Numéro
21
Pages
e2866-e2879
Langue
anglais
Notes
Publication types: Journal Article ; Multicenter Study ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
To define the risks and consequences of cardiac abnormalities in ATP1A3-related syndromes.
Patients meeting clinical diagnostic criteria for rapid-onset dystonia-parkinsonism (RDP), alternating hemiplegia of childhood (AHC), and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS) with ATP1A3 genetic analysis and at least 1 cardiac assessment were included. We evaluated the cardiac phenotype in an Atp1a3 knock-in mouse (Mashl <sup>+/-</sup> ) to determine the sequence of events in seizure-related cardiac death.
Ninety-eight patients with AHC, 9 with RDP, and 3 with CAPOS (63 female, mean age 17 years) were included. Resting ECG abnormalities were found in 52 of 87 (60%) with AHC, 2 of 3 (67%) with CAPOS, and 6 of 9 (67%) with RDP. Serial ECGs showed dynamic changes in 10 of 18 patients with AHC. The first Holter ECG was abnormal in 24 of 65 (37%) cases with AHC and RDP with either repolarization or conduction abnormalities. Echocardiography was normal. Cardiac intervention was required in 3 of 98 (≈3%) patients with AHC. In the mouse model, resting ECGs showed intracardiac conduction delay; during induced seizures, heart block or complete sinus arrest led to death.
We found increased prevalence of ECG dynamic abnormalities in all ATP1A3-related syndromes, with a risk of life-threatening cardiac rhythm abnormalities equivalent to that in established cardiac channelopathies (≈3%). Sudden cardiac death due to conduction abnormality emerged as a seizure-related outcome in murine Atp1a3-related disease. ATP1A3-related syndromes are cardiac diseases and neurologic diseases. We provide guidance to identify patients potentially at higher risk of sudden cardiac death who may benefit from insertion of a pacemaker or implantable cardioverter-defibrillator.
Patients meeting clinical diagnostic criteria for rapid-onset dystonia-parkinsonism (RDP), alternating hemiplegia of childhood (AHC), and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS) with ATP1A3 genetic analysis and at least 1 cardiac assessment were included. We evaluated the cardiac phenotype in an Atp1a3 knock-in mouse (Mashl <sup>+/-</sup> ) to determine the sequence of events in seizure-related cardiac death.
Ninety-eight patients with AHC, 9 with RDP, and 3 with CAPOS (63 female, mean age 17 years) were included. Resting ECG abnormalities were found in 52 of 87 (60%) with AHC, 2 of 3 (67%) with CAPOS, and 6 of 9 (67%) with RDP. Serial ECGs showed dynamic changes in 10 of 18 patients with AHC. The first Holter ECG was abnormal in 24 of 65 (37%) cases with AHC and RDP with either repolarization or conduction abnormalities. Echocardiography was normal. Cardiac intervention was required in 3 of 98 (≈3%) patients with AHC. In the mouse model, resting ECGs showed intracardiac conduction delay; during induced seizures, heart block or complete sinus arrest led to death.
We found increased prevalence of ECG dynamic abnormalities in all ATP1A3-related syndromes, with a risk of life-threatening cardiac rhythm abnormalities equivalent to that in established cardiac channelopathies (≈3%). Sudden cardiac death due to conduction abnormality emerged as a seizure-related outcome in murine Atp1a3-related disease. ATP1A3-related syndromes are cardiac diseases and neurologic diseases. We provide guidance to identify patients potentially at higher risk of sudden cardiac death who may benefit from insertion of a pacemaker or implantable cardioverter-defibrillator.
Mots-clé
Adolescent, Adult, Cerebellar Ataxia/genetics, Cerebellar Ataxia/metabolism, Cerebellar Ataxia/therapy, Child, Child, Preschool, Cohort Studies, Female, Foot Deformities, Congenital/genetics, Foot Deformities, Congenital/metabolism, Foot Deformities, Congenital/therapy, Hearing Loss, Sensorineural/genetics, Hearing Loss, Sensorineural/metabolism, Hearing Loss, Sensorineural/therapy, Hemiplegia/diagnosis, Hemiplegia/genetics, Hemiplegia/therapy, Humans, Infant, Male, Middle Aged, Mutation/genetics, Optic Atrophy/genetics, Optic Atrophy/metabolism, Optic Atrophy/therapy, Phenotype, Reflex, Abnormal/genetics, Seizures/therapy, Sodium-Potassium-Exchanging ATPase/genetics, Young Adult
Pubmed
Web of science
Open Access
Oui
Création de la notice
19/09/2020 14:24
Dernière modification de la notice
08/08/2024 7:40