Mutations in one of these genes, even in heterozygosis (meaning that only 1/6 alleles is affected), is sufficient to lead to an early and severe form of LQTS with extreme long QTc interval secondary to an impaired CaV1.2 inactivation and increased ICaL currents [45,46,47,48,49]. The gene discussed is CACNA1C; the disease is familial long QT syndrome.