Long QT syndrome.

1272 CMAJ, August 9, 2011, 183(11) © 2011 Canadian Medical Association or its licensors In a First Nation community located northeast of Haida Gwaii in British Columbia, a 38-year-old woman required resuscitation from an apparent cardiac arrest that had occurred while she was coaching at a competitive sports event. She had a history of syncope and palpitations. Her family history included a brother who had died unexpectedly as an infant and an aunt who had died suddenly at the age of 15 years. In the same community, a 37-year-old woman had a prolonged QT interval corrected for heart rate (QTc) on electrocardiograms (ECGs), a history of frequent palpitations and brief episodes of altered consciousness and weakness. Her family history included sudden, unexplained death in a newborn sibling and in a sister aged 32 years. The women were diagnosed with long QT syndrome. Clinical genetic sequencing showed they both had a G-to-A substitution in exon 4 of the KCNQ1 gene, resulting in a novel valine-tomethionine amino acid change at position 205 of the protein (V205M). Mechanistic studies subsequently established mutation pathogenicity. These two patients were not known to be related within four generations. The long QT syndrome in both women was managed with implantable cardioverter defibrillators. In a second First Nation community also located northeast of Haida Gwaii, a four-year-old girl complained that her “heart was jumping.” Several ECGs were performed, and community physicians made a clinical diagnosis of long QT syndrome. The child’s paternal aunt had died suddenly after childbirth at age 26, and her father had lost two other siblings as infants to sudden, unexplained death. Because the child’s grandmothers were both ancestrally from community one, it was presumed this family would also carry the KCNQ1 V205M mutation. However, targeted testing was negative for this mutation, and comprehensive molecular testing was done for the five most common long QT syndrome genes: KCNQ1, KCNH2, SCN5A, KCNE1 and KCNE2. Sequencing confirmed that the child and her father shared a different mutation in KCNQ1, R591H, which has been previously characterized as a pathogenic mutation. Other family members have been confirmed as mutation carriers, and a history of sudden, unexplained death can be traced back at least five generations. To date, long QT syndrome in this family has been managed effectively with β-blockers.