The long QT syndrome family of cardiac ion channelopathies: A HuGE review

Abstract

Long QT syndrome (LQTS) refers to a group of "channelopathies"-disorders that affect cardiac ion channels. The "family" concept of syndromes has been applied to the multiple LQTS genotypes, LQT1-8, which exhibit converging mechanisms leading to QT prolongation and slowed ventricular repolarization. The 470ϩ allelic mutations induce loss-of-function in the passage of mainly K ϩ ions, and gain-of-function in the passage of Na ϩ ions through their respective ion channels. Resultant early after depolarizations can lead to a polymorphic form of ventricular tachycardia known as torsade de pointes, resulting in syncope, sudden cardiac death, or near-death (i.e., cardiac arrest aborted either spontaneously or with external defibrillation). LQTS may be either congenital or acquired. The genetic epidemiology of both forms can vary with subpopulation depending on the allele, but as a whole, LQTS appears in every corner of the globe. Many polymorphisms, such as HERG P448R and A915V in Asians, and SCN5A

Impaired endocytosis of the ion channel TRPM4 is associated with human progressive familial heart block type I

“…TRPM4 E7K correlated with elevated density of the TRPM4 channel in the plasma membrane because of attenuated channel deSUMOylation, a mechanism in the etiology of cardiac channelopathies (22,39) that was, to our knowledge, previously unknown. Gain-of-function mutations in ion channels associated with cardiac arrhythmias are relatively rare (40)(41)(42). Ion channel mutations mostly lead to loss of channel function by disrupting subunit assembly, anterograde trafficking, and/or ion channel gating properties (22)(23)(24)(25)(26)(27).…”

El síndrome de QT largo en anestesia. Una revisión a partir de un caso clínico

“…LQT3 se asocia a mutaciones en los canales de sodio voltaje dependientes I Na , otorgán-doles una "ganancia en su función", manteniendo el ingreso de sodio a la célula por más tiempo, prolongando el potencial de acción. Este grupo en general puede manifestar episodios sincopales y muerte súbita en reposo o durante el sueño [25][26][27][28][29][30][31][32] . Todas las variantes de cLQTS presentan aumento de la DRT como factor fisiopatológico clave, independiente de la duración del intervalo QT.…”

Predict, prevent and personalize: Genomic and proteomic approaches to cardiovascular medicine

“…The first causal mutation in the beta-myosin heavy chain was described in a large French-Canadian family in 1990 (25). Monogenic causes have been identified for many other cardiovascular disorders, including dyslipidemia (26), coronary disease (27), dilated cardiomyopathy (28), long QT syndrome (29), arrhythmogenic right ventricular cardiomyopathy (30) and atrial fibrillation (31).…”