The impact of Congenital Long QT Syndrome on First Nations children and youth in Northern British Columbia
Bibliographic record
Abstract
Background: Long QT syndrome (LQTS) is a cardiac condition which predisposes individuals to syncope, seizures, and sudden cardiac death. There is a high prevalence of congenital LQTS in a First Nations community in Northern British Columbia due to the founder variant p.V205M in the KCNQ1 gene. Additionally, two other variants of interest are present in this population: the KCNQ1 p.L353L variant, previously noted to modify the phenotype of LQTS in adults, and the CPT1A p.P479L variant, a metabolic variant common in Northern Indigenous populations associated with hypoglycemia and sudden unexpected infant death. Methods: We performed a mixed methods study to better understand the impact of LQTS in children and youth in this First Nations community. To learn about the clinical impact of LQTS, and better understand the effects of the KCNQ1 and CPT1A variants in children, we used statistical analysis to compare the cardiac phenotypes of 211 First Nations children with and without the p.V205M, p.L353L and p.P479L variants, alone and in combination. Ordinary Least Squares linear regression was used to compare the highest peak corrected QT interval (QTc). The peak QTc is an electrocardiogram measurement used in risk stratification of LQTS patients. Logistic regression was used to compare the rates of syncope and seizures experienced in childhood. Additionally, to learn about the lived-experience of LQTS, we interviewed one young First Nations adult about her experiences growing up with LQTS as a teenager. From this interview, we conducted a qualitative case study analysis using Interpretative Phenomenological Analysis. All research was done in partnership with the First Nations community using community-based participatory methods. Results: We found that the p.V205M variant conferred a 22.4ms increase in peak QTc (p<0.001). No other variants or variant interaction effects were observed to have a significant impact on peak QTc. No association between the p.V205M variant and loss of consciousness (LOC) events (syncope and seizures) was observed (OR(95%CI)=1.3(0.6-2.8); p=0.531). However, children homozygous for p.P479L were found to experience 3.3 times more LOC events compared to non-carriers (OR=3.3(1.3-8.3); p=0.011). With regard to the qualitative portion of the thesis, four superordinate (main) themes emerged from the case study: Daily life with Long QT Syndrome, Interactions with Medical Professionals, Finding Reassurance, and The In-Between Age. We found that even though our participant was asymptomatic and felt that she was not impacted by LQTS in her daily life, she considered certain elements of the condition to be stressful, such as taking a daily beta-blocker. Conclusion: These results suggest that while the KCNQ1 p.V205M variant is observed to significantly prolong the peak QTc, the CPT1A p.P479L variant is more strongly associated with LOC events in children from this community. More research is needed to further determine the effect of these variants; however, our preliminary findings suggest management strategies, such as whether beta-blockers are indicated for p.V205M carriers, may need to be reassessed. The importance of developing a holistic, well-balanced approach to medical care, taking into consideration the personal perspectives and unique medical circumstances of each child is exemplified in this study.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.003 |
| Science and technology studies | 0.003 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".