Abstract 5693: Detection of a Founder Effect in LQT1 in Five Apparently Unrelated Families in a Regional Inherited Arrhythmia Clinic
The Inherited Arrhythmia Clinic follows families with inherited arrhythmia syndromes from a population of 1.5 million people. Patients referred for evaluation of Long QT Syndrome (LQTS) underwent resting and standing ECGs, and 3 forms of exercise. Patients with findings consistent with LQTS underwent genetic testing, with assessment of all 1st degreerelatives. A proband from each of 5 unrelated families was found to have an identical disease causing transmembrane mutation in KCNQ1, suggesting a founder effect (Exon 6, 797 T>C). Systematic screening of 1st degree relative of affected individuals was performed. 31 patients (age 42±24yrs (range 4 – 89 years), 18 female) were identified from the 5 families, including the 5 probands. All affected individuals were offered beta-blockers. 18 affected family members and 13 unaffected 1st degree relatives were identified. Several family members had malignant presentations including sudden death and unexplained drowning. One proband had torsades de pointes during an exercise test. Other family members were asymptomatic until their 8th and 9th decades when they developed cardiac ischemia and had further QT prolongation, torsades de pointes and cardiac arrest. Sudden death occurred in a deaf child; both of the child’s consanguineous parents were gene positive for the KCNQ1 mutation (Jervell and Lange-Nielsen Syndrome). There was no identifiable common relative after pedigree construction of the previous 4 –7 generations. Affected patients typically had borderline QT prolongation at rest with dramatic prolongation with exercise (Table⇓). Genetic testing in this LQTS population suggests a founder effect for the five families with the descendants clustering in our geographical region. The observations highlight the utility of genetic testing when used in conjunction with a specialized clinic setting.