@article{3193475,
    title = "Cardiac phenotype in ATP1A3-related syndromes A multicenter cohort study",
    author = "Balestrini, Simona and Mikati, Mohamad A. and Alvarez-Garcia-Roves, and Reyes and Carboni, Michael and Hunanyan, Arsen S. and Kherallah, Bassil and and McLean, Melissa and Prange, Lyndsey and De Grandis, Elisa and and Gagliardi, Alessandra and Pisciotta, Livia and Stagnaro, Michela and and Veneselli, Edvige and Campistol, Jaume and Fons, Carmen and and Pias-Peleteiro, Leticia and Brashear, Allison and Miller, Charlotte and and Samoes, Raquel and Brankovic, Vesna and Padiath, Quasar S. and Potic, and Ana and Pilch, Jacek and Vezyroglou, Aikaterini and Bye, Ann M. E. and and Davis, Andrew M. and Ryan, Monique M. and Semsarian, Christopher and and Hollingsworth, Georgina and Scheffer, Ingrid E. and Granata, Tiziana and and Nardocci, Nardo and Ragona, Francesca and Arzimanoglou, Alexis and and Panagiotakaki, Eleni and Carrilho, Ines and Zucca, Claudio and Novy, Jan and and Parowicz, Marek and Weckhuysen, Sarah and Pons, Roser and Groppa, and Sergiu and Sinden, Daniel S. and Pitt, Geoffrey S. and Tinker, Andrew and and Ashworth, Michael and Michalak, Zuzanna and Thom, Maria and Cross, and J. Helen and Vavassori, Rosaria and Kaski, Juan P. and Sisodiya, Sanjay and M. and Dzieiyc, Karolina and Mazurkiewicz-Beldzinska, Maria",
    journal = "Functional Neurology",
    year = "2020",
    volume = "95",
    number = "21",
    pages = "E2866-E2879",
    publisher = "Lippincott, Williams & Wilkins",
    doi = "10.1212/WNL.0000000000010794",
    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 (approximate to 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
(approximate to 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."
}