Congenital Long QT Syndrome with Compound Mutations in KCNH2 Gene

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We report a case with long QT syndrome caused by compound mutations in KCNH2 gene. A 20-year-old man was referred to our hospital for evaluation of syncope. When he was a high school student, he experienced syncope. In electrocardiogram, the QT interval was prolonged to 498 ms (QTc=479 ms). His 22-year-old elder brother, who had syncopal episodes twice and the prolonged QT interval in electrocardiogram, suffered from ventricular fibrillation and became vegetative state on May 26, 2009. Genetic testing revealed the frameshift mutation by the insertion of 25 nucleotides causing both an altered amino acid sequence from codon 302 and a premature termination codon (i.e., TAG) at codon 339 and the missense mutation of c.1474 C>T (p.H492Y) in KCNH2 gene in both brothers. These mutations have not been reported previously. Family genetic screening found that their father had the same fameshift mutation and their mother and sister had the same missense mutation in KCNH2 gene. However the family members without two brothers experienced no symptoms and had no prolonged QT interval in electrocardiogram. These results suggest that the compound mutations in KCNH2 gene inherited independently from the parents made the phenotype of their sons more severe. Then we planted the implantable cardioverter defibrillator into him on March 17, 2010.