Diagnostic Accuracy of Clinical Manifestations in Identifying People With Tuberous Sclerosis Complex
Why this work is in the frame
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Bibliographic record
Abstract
Background and Objectives: and are diagnosed clinically. In such situations, family members cannot be screened using genetic testing. We aimed to establish the diagnostic accuracy of TSC clinical features to better guide the screening process for the families of PwTSC. Methods: We used the TSC Natural History Database, a longitudinal database of PwTSC from 22 North American centers. We used a definite genetic TSC diagnosis as our gold standard. We estimated the sensitivity (95% CI) of TSC-related skin, structural brain, renal, and cardiac manifestations, as well as combinations of these manifestations. Using a series of sensitivity analyses to test alternate assumptions, we estimated positive predictive values and negative predictive values (PPVs and NPVs). Results: Among the 1,300 genetics-positive PwTSC, 50.3% were female and the mean age at diagnosis was 3.7 years. The sensitivity of at least one skin or structural brain manifestation was 98.7% (95% CI 98.0-99.2). The PPV and NPV were 83.2 (95% CI 81.6-84.6) and 98.4% (95% CI 97.8-98.8), respectively, while assuming 50% prevalence and 80% specificity. Including cardiac manifestations marginally increased the sensitivity, PPV, and NPV to 99.5% (95% CI 98.9-99.7), 83.3% (95% CI 81.8-84.7), and 99.4% (95% CI 99.0-99.6), respectively. Other combinations of TSC manifestations had lower or similar diagnostic accuracy. Discussion: Assessment of brain and skin manifestations in family members of genetics-positive PwTSC is sufficient to screen for TSC in most cases, with excellent sensitivity and NPV. Our findings are potentially applicable to family members of genetics-negative PwTSC. Further cardiac screening may optimize diagnostic accuracy in selected cases. Classification of Evidence: This study provides Class IV evidence that a combination of brain and skin manifestations is highly sensitive for diagnosing TSC in family members of patients with genetically confirmed TSC.
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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 | 0.002 |
| 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 | 0.001 |
| 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 it