Calmodulin interacts with several ion channels and its roles include modulation of the L-type calcium current in response to calcium concentrations, and trafficking the proteins produced by KCNQ1 and thereby influencing potassium currents. The precise mechanisms by which means these genetic variants prolong the QT interval remain uncertain.Table of causative genes

Mechanism
In the Romano-Ward forms of Long QT syndrome, genetic mutations affect how positively-charged ions, such as potassium, sodium and calcium ions are transported in and out of heart cells. Many of these genes encode proteins which form or interact with ion channels. In cardiac muscle, these ion channels play critical roles in maintaining the hearts normal rhythm. Mutations in any of these genes alter the structure or function of channels, which changes the flow of ions between cells, a disruption in ion transport alters the way the heart beats, leading to abnormal heart rhythm characteristic of the syndrome.The protein made by the ANK2 gene ensures that other proteins, particularly ion channels, are inserted into the cell membrane appropriately. A mutation in the ANK2 gene likely alters the flow of ions between cells in the heart, which disrupts the hearts normal rhythm and results in the features of Romano–Ward syndrome. Diagnosis
Romano–Ward syndrome is principally diagnosed by measuring the QT interval corrected for heart rate (QTc) on a 12-lead electrocardiogram (ECG). Romano–Ward syndrome is associated with a prolonged QTc, although in some genetically proven cases of Romano–Ward syndrome this prolongation can be hidden, known as concealed Long QT syndrome.
Romano–Ward syndrome is the most common form of congenital Long QT syndrome (LQTS), a genetic heart condition that affects the electrical properties of heart muscle cells. Those affected are at risk of abnormal heart rhythms which can lead to fainting, seizures, or sudden death. Romano–Ward syndrome can be distinguished clinically from other forms of inherited LQTS as it affects only the electrical properties of the heart, while other forms of LQTS can also affect other parts of the body. Romano–Ward syndrome is caused by abnormal variants in the genes responsible for producing certain proteins used to transport charged particles (ion channels) within the heart. These abnormalities interfere with the electrical signals that heart cells use to coordinate contractions, causing the heart to take longer to recharge in between beats. The condition is usually diagnosed using an electrocardiogram, but other tests sometimes used include Holter monitoring, exercise testing, and genetic testing. It may be treated using medications such as beta-blockers, an implantable cardioverter-defibrillator, or surgery to disrupt the sympathetic nervous system. Romano–Ward syndrome is estimated to affect 1 in every 7,000 people. Signs and symptoms
Romano–Ward syndrome increases the risk of abnormal heart rhythms or arrhythmias. These are typically a form of ventricular tachycardia known as Torsades de pointes which can cause faints, seizures, or even sudden death. Less dangerous arrhythmias such as atrial fibrillation also occur, causing symptoms of heart racing or palpitations. However, many of those with Romano–Ward syndrome will remain free from arrhythmias and therefore free from symptoms.