Cardiac phenotype in ATP1A3-related syndromes
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Published:2020-09-10
Issue:21
Volume:95
Page:e2866-e2879
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ISSN:0028-3878
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Container-title:Neurology
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language:en
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Short-container-title:Neurology
Author:
Balestrini SimonaORCID, Mikati Mohamad A., Álvarez-García-Rovés Reyes, Carboni MichaelORCID, Hunanyan Arsen S., Kherallah Bassil, McLean Melissa, Prange Lyndsey, De Grandis Elisa, Gagliardi Alessandra, Pisciotta LiviaORCID, Stagnaro Michela, Veneselli Edvige, Campistol Jaume, Fons Carmen, Pias-Peleteiro Leticia, Brashear AllisonORCID, Miller Charlotte, Samões Raquel, Brankovic Vesna, Padiath Quasar S., Potic Ana, Pilch JacekORCID, Vezyroglou Aikaterini, Bye Ann M.E.ORCID, Davis Andrew M.ORCID, Ryan Monique M.ORCID, Semsarian Christopher, Hollingsworth Georgina, Scheffer Ingrid E., Granata Tiziana, Nardocci Nardo, Ragona Francesca, Arzimanoglou AlexisORCID, Panagiotakaki Eleni, Carrilho Inês, Zucca Claudio, Novy Jan, Dzieżyc Karolina, Parowicz Marek, Mazurkiewicz-Bełdzińska MariaORCID, Weckhuysen SarahORCID, Pons Roser, Groppa Sergiu, Sinden Daniel S., Pitt Geoffrey S., Tinker Andrew, Ashworth Michael, Michalak Zuzanna, Thom MariaORCID, Cross J. Helen, Vavassori Rosaria, Kaski Juan P.ORCID, Sisodiya Sanjay M.
Abstract
ObjectiveTo define the risks and consequences of cardiac abnormalities in ATP1A3-related syndromes.MethodsPatients 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.ResultsNinety-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.ConclusionsWe 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.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Neurology (clinical)
Reference38 articles.
1. De novo mutations in ATP1A3 cause alternating hemiplegia of childhood 2. Mutations in the Na+/K+-ATPase α3 Gene ATP1A3 Are Associated with Rapid-Onset Dystonia Parkinsonism 3. A novel recurrent mutation in ATP1A3 causes CAPOS syndrome 4. Brashear A , Sweadner KJ , Cook JF , Swoboda KJ , Ozelius L . ATP1A3-Related neurologic disorders. 2008. In: Adam MP , Ardinger HH , Pagon RA , et al ., editors. GeneReviews® [Internet]. Seattle: University of Washington; 1993–2018. Available at: ncbi.nlm.nih.gov/books/NBK1115/. Accessed January 5, 2019. 5. Diagnosis and treatment of alternating hemiplegia of childhood;Masoud;Curr Treat Options Neurol,2017
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