From OMIM
Cardiac arrhythmia syndrome with or without skeletal muscle weakness (CARDAR) is characterized by onset of exercise- or emotion-induced cardiac arrhythmias in infancy or early childhood, associated with syncope or cardiac arrest. Electrocardiography shows variable abnormalities, including polymorphic or bidirectional ventricular extrasystoles and/or transient or persistent prolonged QT intervals, as well as inverted T-waves across the precordial leads. Cardiac events are refractory to both beta-blockers and left cardiac sympathetic denervation. Skeletal muscle weakness has been reported in some patients (Roux-Buisson et al., 2012; Altmann et al., 2015). Reviews Giudicessi and Ackerman (2016) reviewed the role of Ca(2+) cycling in cardiac repolarization and in the pathogenesis of long QT-associated cardiac arrhythmias. They noted that TRDN-null mouse models show remodeling of the calcium release unit molecular architecture, implicating either early or delayed after-depolarization as the mechanism predominantly responsible for the observed ventricular arrhythmias. Clemens et al. (2019) established an International Triadin Knockout Syndrome Registry and reviewed 14 previously published patients with TRDN-associated cardiac arrhythmias, as well as 7 additional patients. Affected individuals presented with either cardiac arrest or syncope at an average age of 3 years. The most common trigger was physical exertion, although a large number of events were not associated with a specific trigger. Mild skeletal myopathy or slight proximal muscle weakness was observed in 6 (29%) of the patients. Two patients died after cardiac events. Of the 19 surviving patients, 16 (84%) showed T-wave inversions across precordial leads, extending to V3 or V4, and 10 (53%) had transient QT prolongation greater than 480 ms. In addition, 8 (89%) of 9 patients who underwent exercise stress testing exhibited ventricular ectopy. All 16 patients tested had normal echocardiograms. The 19 surviving patients were treated with beta-blockers, and 13 (68%) also received implantable defibrillators; however, despite treatment, 14 (74%) of the patients experienced recurrent breakthrough cardiac events.  http://www.omim.org/entry/615441