A mild phenotype associated with KCNQ1 p.V205M mediated long QT syndrome in First Nations children of Northern British Columbia: effect of additional variants and considerations for management

• Published in: Frontiers in pediatrics 2024-05, Vol.12, p.1394105-1394105
• Main Authors: Bene Watts, Simona, Gauthier, Barbara, Erickson, Anders C, Morrison, Julie, Sebastian, Mavis, Gillman, Lawrence, McIntosh, Sarah, Ens, Connie, Sherwin, Elizabeth, McCormick, Rod, Sanatani, Shubhayan, Arbour, Laura
• Format: Article
• Language: English
• Subjects: carnitine palmitoyltransferase 1A; First Nations; Indigenous; KCNQ1; long QT syndrome (LQTS); long QT syndrome type 1; Pediatrics
• ISSN: 2296-2360; 2296-2360
• DOI: 10.3389/fped.2024.1394105

Congenital Long QT Syndrome (LQTS) is common in a First Nations community in Northern British Columbia due to the founder variant p.V205M. Although well characterized molecularly and clinically in adults, no data have been previously reported on the pediatric population. The phenotype in adults has been shown to be modified by a splice site variant in (p.L353L). The p.P479L metabolic variant, also common in Northern Indigenous populations, is associated with hypoglycemia and infant death. Since hypoglycemia can affect the corrected QT interval (QTc) and may confer risk for seizures (also associated with LQTS), we sought to determine the effect of all three variants on the LQTS phenotype in children within our First Nations cohort. As part of a larger study assessing those with LQTS and their relatives in a Northern BC First Nation, we assessed those entering the study from birth to age 18 years. We compared the corrected peak QTc and potential cardiac events (syncope/seizures) of 186 children from birth to 18 years, with and without the (p.V205M and p.L353L) and variants, alone and in combination. Linear and logistic regression and student -tests were applied as appropriate. Only the p.V205M variant conferred a significant increase in peak QTc 23.8 ms (