The QTc is less than 450 ms in 95% of normal males, and less than 460 ms in 95% of normal females. Romano–Ward syndrome is suggested if the QTc is longer than these cutoffs. However, as 5% of normal people also fall into this category, some suggest cutoffs of 470 and 480 ms for males and females respectively, corresponding with the 99th centiles of normal values.The major subtypes of Romano–Ward syndrome are associated with specific ECG features. LQT1 is typically associated with broad-based T-waves, whereas the T-waves in LQT2 are notched and of lower amplitude, whilst in LQT3 the T-waves are often late onset, being preceded by a long isoelectric segment.Other factors beyond the QT interval should be taken into account when making a diagnosis, some of which have been incorporated into scoring systems such as the Schwartz score. These factors include a history of characteristic abnormal heart rhythms (Torsades de Pointes), unexplained blackouts (syncope), and a family history of confirmed LQT syndrome. 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). Treatment
The treatment for Romano–Ward syndrome aims to reduce the risk of arrhythmias. Lifestyle measures include avoiding very strenuous or competitive exercise.
SCN5A encodes the alpha subunit of the cardiac sodium channel, NaV1.5, responsible for the sodium current INa which depolarises cardiac cells at the start of the action potential. Cardiac sodium channels normally inactivate rapidly, but the mutations involved in LQT3 slow their inactivation leading to a small sustained late sodium current. This continued inward current prolongs the action potential and thereby the QT interval.A large number of mutations have been characterized as leading to or predisposing to LQT3. Calcium has been suggested as a regulator of SCN5A protein, and the effects of calcium on SCN5A may begin to explain the mechanism by which some of these mutations cause LQT3. Furthermore, mutations in SCN5A can cause Brugada syndrome, cardiac conduction disease, and dilated cardiomyopathy. In rare situations, some individuals can have combinations of these diseases. Other subtypes
LQT5 is caused by variants in the KCNE1 gene. This gene is responsible for the potassium channel beta subunit MinK which, in conjunction with the alpha subunit encoded by KCNQ1, is responsible for the potassium current IKs, and variants associated with prolonged QT intervals decrease this current. The same variants in KCNE1 can cause the more severe Jervell and Lange-Nielsen syndrome when two copies are inherited (homozygous inheritance) and the milder LQT5 subtype of Romano–Ward syndrome when a single copy of the variant is inherited (heterozygous inheritance).The LQT6 subtype is caused by variants in the KCNE2 gene.