Heterosynaptic NMDA receptor plasticity in hippocampal dentate granule cells.

Calmodulin (CaM) is a ubiquitous calcium-binding messenger protein encoded by , , and . It regulates numerous ion channels and signaling pathways in cardiomyocytes (). Since the first report in 2012 linking mutations to ventricular tachycardia and sudden cardiac death, calmodulinopathy has been recognized as an important genetic etiology of malignant arrhythmias in children (, ). The clinical presentation of calmodulinopathy is heterogeneous, manifesting as long QT syndrome (LQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT), an overlap phenotype in which both manifestations coexist (LQTS/CPVT), or idiopathic ventricular fibrillation. The overlap phenotype is characterized by concurrent QTc prolongation and catecholamine-induced bidirectional/polymorphic ventricular tachycardia. This entity is clinically rare and poses greater challenges in diagnosis and management (). The article reports two independent Chinese pediatric cases of LQTS/CPVT overlap phenotype associated with gene mutations, and discusses their clinical characteristics, genetic basis, and treatment strategies in the context of a literature review. A 13-year-old Chinese girl presented with recurrent syncope within 15 months. She experienced a total of 7 episodes, all occurring during strenuous exercise (for example, fast running, fast cycling or frog jumps). The episodes were characterized by no prodrome, collapse with loss of consciousness, no convulsions, with or without urinary incontinence, lasting less than 10 min, although the exact durations were unknown. Any exercise-related chest pain was denied. Besides, she occasionally experienced palpitations and dizziness when climbing upstairs. She was born at 36 weeks of gestation. The motor and mental development were normal. There was no family history of inherited cardiovascular disease, sudden cardiac death, or drowning.