Recent discoveries of genes involved in long-QT syndrome (LQTS) have led to 
extensive progress in understanding the molecular basis for this disorder of 
syncope and sudden cardiac death secondary to ventricular arrhythmias. The 
emerging unifying theme is that all genes identified to date encode either 
structural or regulatory subunits for ion channels involved in cardiac 
repolarization. Defects have been identified in the KCNQ1, HERG, and KCNE1 
genes, whose proteins form the K+ channels for the slowly and rapidly inwardly 
rectifying K+ currents IKs and IKr. Depending on their location and copy number, 
mutations of KCNQ1 and KCNE1 can cause either autosomal dominant Romano-Ward 
syndrome or autosomal recessive Jervell and Lange-Nielsen syndrome. The cardiac 
sodium channel gene, SCN5A, is also mutated in some Romano-Ward cases to produce 
defects in INa, the cardiac inward Na+ current. The fact that multiple genes are 
involved and that most LQTS mutations are "private" or "family-specific" 
complicates molecular diagnosis of LQTS which, currently, is limited to a small 
number of research laboratories. In future, genotypic determination of LQTS 
patients and their family members will hopefully lead to improved gene-specific 
prognostic determinations and therapeutic interventions.