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Brugada Syndrome: Clinical Care Amidst Pathophysiological Uncertainty. Brugada syndrome (BrS) is a complex clinical entity with ongoing conjecture regarding its genetic basis, underlying pathophysiology, and clinical management. Within this paradigm of uncertainty, clinicians are faced with the challenge of caring for patients with this uncommon but potentially fatal condition. This article reviews the current understanding of BrS and highlights the "known unknowns" to reinforce the need for flexible clinical practice in parallel with ongoing scientific discovery.