Intellectual and Neurodevelopmental Delays in Pediatric Catecholaminergic Polymorphic Ventricular Tachycardia: Distinct Characteristics and a More Malignant Neurocardiac Phenotype
Bibliographic record
Abstract
BACKGROUND: Marked intellectual and neurodevelopmental delay (INDD) was noted in 6 unrelated patients diagnosed with RYR2 -related catecholaminergic polymorphic ventricular tachycardia (CPVT) from a single center. Patients exhibited similar distinct phenotypic features not previously described. We aimed to determine the prevalence of INDD in CPVT, compare clinical characteristics between patients with CPVT with and without INDD, and investigate the possibility of a unique neurocardiac CPVT phenotype. METHODS: Retrospective combined review of patients with RYR2 -related CPVT diagnosed ≤18 years with and without INDD from a single center and the International Pediatric CPVT Registry. Patients with hypoxic ischemic insult were excluded unless INDD preceded injury. RESULTS: Among a total of 168 patients, INDD was reported in 19 (11.3% [95% CI, 7.0%–17.1%]). When compared with cases without INDD, patients with INDD exhibited distinct features including (1) younger age at onset of symptoms (median 7.0 versus 10.0 years; P =0.04); (2) higher frequency of atrial tachyarrhythmias (84.2% versus 16.3%, P <0.001); (3) atrial or ventricular tachycardia without adrenergic stimulation (81.3% versus 2.2%, P <0.001, 31.6% versus 4.5%, P =0.001 respectively); (4) cardiac structural changes or systolic dysfunction (36.8% versus 1.3%, P <0.001); and (5) higher incidence of cardiac arrest or sudden death after diagnosis (26.3% versus 2.7%, P =0.001). INDD-related RYR2 genetic variants clustered within the central and channel domains and may be specific to certain variants. CONCLUSIONS: This study demonstrates a wider spectrum of RYR2 -related disease, with a subset associated with extracardiac manifestations. Certain RYR2 variants may lead to a neurocardiac phenotype with distinct features that are important to recognize, as these patients may be at higher risk.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".