|
Title
|
|
|
|
Cardiac phenotype in ATP1A3-related syndromes : a multicenter cohort study
| |
|
Author
|
|
|
|
| |
|
Abstract
|
|
|
|
| Objective To define the risks and consequences of cardiac abnormalities in ATP1A3-related syndromes. Methods 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+/−) to determine the sequence of events in seizure-related cardiac death. Results 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. Conclusions 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. |
| |
|
Language
|
|
|
|
English
| |
|
Source (journal)
|
|
|
|
Neurology / American Academy of Neurology. - Minneapolis, Minn
| |
|
Publication
|
|
|
|
Minneapolis, Minn
:
2020
| |
|
ISSN
|
|
|
|
0028-3878
| |
|
DOI
|
|
|
|
10.1212/WNL.0000000000010794
| |
|
Volume/pages
|
|
|
|
95
:21
(2020)
, p. e2866-e2879
| |
|
ISI
|
|
|
|
000619288500004
| |
|
Pubmed ID
|
|
|
|
32913013
| |
|
Full text (Publisher's DOI)
|
|
|
|
| |
|
Full text (open access)
|
|
|
|
| |
|