1215Neurodevelopmental disorders in patients with RYR2-associated catecholaminergic polymorphic ventricular tachycardia
Bibliographic record
Abstract
Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare inherited cardiac disorder characterized by adrenergically-evoked ventricular arrhythmias. Mutations in the cardiac ryanodine receptor gene (RYR2) are identified in the majority of patients with CPVT. RyR2 is the major RyR isoform expressed in the brain. Purpose: To estimate the prevalence of intellectual disability (ID) and other neurodevelopmental disorders (NDDs) in RYR2-associated CPVT (CPVT1) and to study the clinical characteristics of this patient subgroup. Methods: We reviewed the medical records of all CPVT1 patients from fourteen tertiary referral centers in Japan, the United States, the United Kingdom, and the Netherlands. We identified all patients with CPVT and concomitant ID. Results: Among 370 patients with CPVT1, we identified 33 patients (9%) with concomitant ID with or without other NDDs. In all cases the ID was diagnosed before the onset of CPVT symptoms. Sixteen patients (49%) were male, median age at diagnosis of CPVT was 9.4 (quartiles 7.1–15.8) years. Parents were available for genetic testing in 23 patients, of whom a de novo mutation was identified in 12 (52%). In three families the RYR2 mutation cosegregated with the ID. The RYR2 mutations (22 missense and 1 splice site) clustered in the known hot-spot regions of the gene, in a three-dimensional structure of RyR2, 10 mutations (43%) clustered in the central domain. The severity of ID ranged from mild to severe, and was accompanied by other NDDs in 12 patients (36%). Thirty patients (91%) had a history of cardiac symptoms and showed ventricular arrhythmias and seventeen patients (52%) had supraventricular tachyarrhythmias. In four patients (12%) supraventricular arrhythmias were the first presenting cardiac symptom. All but one patient were treated with β-blockers, which was combined with flecainide in 17 (53%). During a median follow up of 7.4 (quartiles 1.7–12.4) years, 12 patients (38%) experienced an arrhythmic event.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".