Intrauterine and neonatal manifestations of congenital long QT syndrome are associated with a high cardiac risk, particularly when atrioventricular block and excessive QT prolongation (> 600 ms^1/2) are present. In a female newborn with these features, treatment with propranolol and mexiletine led to complete reduction of arrhythmia that was maintained 1.5 years later. High throughput genetic analysis found a sodium channel gene (LQT3) mutation. Disappearance of the 2:1 atrioventricular block and QTc shortening (from 740 ms^1/2 to 480 ms^1/2), however, was achieved when mexiletine was added to propranolol. This effect was considered to be possibly genotype related. Early onset forms of long QT syndrome may benefit from advanced genotyping.