Long QT Syndrome:

Point of View. Long QT syndrome type 1 (LQFI) causes torsades de pointes arrhythmia, ventricular fibrillation, and sudden death. It usually is inherited as an autosomal dominant trait (Romano‐Ward syndrome). The primary defect in LQTI is a mutation in KVLQT1 , a gene that encodes the pore‐forming α‐subunit of a K + channel. KvLQT1 α‐subunits coassemble with minK β‐subunits to form channels that conduct the slow delayed rectifier K + current (I Ks ) in the heart. Recessive mutations in KVLQT1 cause Jervell and Lange‐Nielsen syndrome, which is characterized by more severe arrhythmias and congenital neural deafness. Heterologous expression studies demonstrated that mutations in KVLQT1 reduce I Ks by causing loss of channel function, altered channel gating, and/or a dominant‐negative effect. It remains to be proven that an understanding of the molecular basis of LQT1 will lead to more effective therapy.