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.

[1] It may be treated using medications such as beta-blockers, an implantable cardioverter-defibrillator, or surgery to disrupt the sympathetic nervous system.

These are typically a form of ventricular tachycardia known as Torsades de pointes which can cause faints, seizures, or even sudden death.

[1] Less dangerous arrhythmias such as atrial fibrillation also occur, causing symptoms of heart racing or palpitations.

However, there is uncertainty as to whether some of the other rarer subtypes are truly disease-causing by themselves or instead make individuals more susceptible to QT prolongation in response to other factors such as medication or low blood potassium levels (hypokalaemia).

Loss-of-function mutations, commonly found in the voltage-sensing domain of the protein, often result in impaired trafficking to the cell surface at levels significantly lower than wild-type.

This current contributes to the terminal repolarisation phase of the cardiac action potential, and therefore the length of the QT interval.

[5] Caveolins form specific membrane domains called caveolae in which voltage-gated sodium channels sit.

Similar to LQT3, these caveolin variants increase the late sustained sodium current, which impairs cellular repolarization.

[5] The precise mechanisms by which means these genetic variants prolong the QT interval remain uncertain.

In cardiac muscle, these ion channels play critical roles in maintaining the heart's normal rhythm.

[medical citation needed] Romano–Ward syndrome is principally diagnosed by measuring the QT interval corrected for heart rate (QTc) on a 12-lead electrocardiogram (ECG).

Other investigations that may suggest a diagnosis of the LQT1 form of Romano–Ward syndrome include paradoxical lengthening of the QT interval in response to exercise (QTc >470 ms at 2–4 minutes of recovery) or during an artificial infusion of adrenaline (lengthening of the absolute QT interval >30 ms during low dose adrenaline).

[1] Those with the LQT2 form of Romano–Ward syndrome should avoid sudden loud noises such as alarm clocks as these may trigger arrhythmias.

[1] Medications that further prolong the QT interval such as sotalol should be avoided, lists of which can be found in publicly accessible online databases.

[8] Beta blockers such as propranolol or nadolol blunt the effects of adrenaline on the heart and thereby reduce the risk of arrhythmias.

These devices are recommended for those with Romano–Ward syndrome who have experienced a cardiac arrest or a blackout whilst taking beta blockers.

[8] In those who experience recurrent arrhythmias despite medical therapy, a surgical procedure called sympathetic denervation can be used to interrupt the nerves that stimulate the heart.