Female predominance and transmission distortion in the long-QT syndrome

Medea Imboden, Heikki Swan, Isabelle Denjoy, Irene Marijke Van Langen, Päivi Johanna Latinen-Forsblom, Carlo Napolitano, Véronique Fressart, Guenter Breithardt, Myriam Berthet, Silvia Priori, Bernard Hainque, Arthur Arnold Maria Wilde, Eric Schulze-Bahr, Josué Feingold, Pascale Guicheney

Research output: Contribution to journalArticlepeer-review


BACKGROUND: Congenital long-QT syndrome is a disorder resulting in ventricular arrhythmias and sudden death. The most common forms of the long-QT syndrome, types 1 and 2, are caused by mutations in the potassium-channel genes KCNQ1 and KCNH2, respectively. Although inheritance of the long-QT syndrome is autosomal dominant, female predominance has often been observed and has been attributed to an increased susceptibility to cardiac arrhythmias in women. We investigated the possibility of an unbalanced transmission of the deleterious trait. METHODS: We investigated the distribution of alleles for the long-QT syndrome in 484 nuclear families with type 1 disease and 269 nuclear families with type 2 disease, all with fully genotyped offspring. The families were recruited in five European referral centers for the long-QT syndrome. Mutation segregation, sex ratio, and parental transmission were analyzed after correction for single ascertainment. RESULTS: Classic mendelian inheritance ratios were not observed in the offspring of either female carriers of the long-QT syndrome type 1 or male and female carriers of the long-QT syndrome type 2. Among the 1534 descendants, the proportion of genetically affected offspring was significantly greater than that expected according to mendelian inheritance: 870 were carriers of a mutation (57%), and 664 were noncarriers (43%, P

Original languageEnglish
Pages (from-to)2744-2751
Number of pages8
JournalNew England Journal of Medicine
Issue number26
Publication statusPublished - Dec 28 2006

ASJC Scopus subject areas

  • Medicine(all)


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