Περίληψη:
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.
Συγγραφείς:
Balestrini, Simona
Mikati, Mohamad A.
Alvarez-Garcia-Roves,
Reyes
Carboni, Michael
Hunanyan, Arsen S.
Kherallah, Bassil
and McLean, Melissa
Prange, Lyndsey
De Grandis, Elisa and
Gagliardi, Alessandra
Pisciotta, Livia
Stagnaro, Michela and
Veneselli, Edvige
Campistol, Jaume
Fons, Carmen and
Pias-Peleteiro, Leticia
Brashear, Allison
Miller, Charlotte and
Samoes, Raquel
Brankovic, Vesna
Padiath, Quasar S.
Potic,
Ana
Pilch, Jacek
Vezyroglou, Aikaterini
Bye, Ann M. E. and
Davis, Andrew M.
Ryan, Monique M.
Semsarian, Christopher and
Hollingsworth, Georgina
Scheffer, Ingrid E.
Granata, Tiziana and
Nardocci, Nardo
Ragona, Francesca
Arzimanoglou, Alexis and
Panagiotakaki, Eleni
Carrilho, Ines
Zucca, Claudio
Novy, Jan
and Parowicz, Marek
Weckhuysen, Sarah
Pons, Roser
Groppa,
Sergiu
Sinden, Daniel S.
Pitt, Geoffrey S.
Tinker, Andrew
and Ashworth, Michael
Michalak, Zuzanna
Thom, Maria
Cross,
J. Helen
Vavassori, Rosaria
Kaski, Juan P.
Sisodiya, Sanjay
M.
Dzieiyc, Karolina
Mazurkiewicz-Beldzinska, Maria
