Long QT interval syndrome- Genetics

Genetics 12 different genes have been linked to LQTS (3) Incomplete penetrance makes both diagnosis and management of asymptomatic disease challenging. IKs- Slow Potassium Channels IKr- Rapid Potassium Channels

• LQTS 1 (42-54%) is the most common. Mutation causes a defect in the IKs transport protein. Arrhythmias can be triggered by tachycardia due to exercise (swimming seems to be especially problematic) and other high catecholamine states.
• LQTS 2 (35-45%) is a defect in the IKr transport protein that is sensitive to catecholamine surges. Sudden loud noises or emotional arousal can provoke arrhythmias.
• LQTS 3 (8%) is a defect in the sodium channel that allows an excess of sodium into the cell, increasing repolarization time. Arrhythmias tend to manifest more during rest or sleep.

Jervell and Lange-Nielsen syndrome: Autosomal recessive form of LQTS that features homozygous mutations affect the IKs channel and presents with severe form of LQTS 1. Features also include deafness. Romano-Ward syndrome: autosomal dominant form of LQTS with variable penetrance. Hearing is normal.