Elucidating the diagnostic odyssey of 22q11.2 deletion syndrome
Bibliographic record
Abstract
Clinical molecular testing has been available for 22q11.2 deletion syndrome (22q11.2DS) for over two decades yet under-recognition and diagnostic delays are common. To characterize the "diagnostic odyssey" in 22q11.2DS we studied 202 well-characterized unrelated adults, none ascertained through an affected relative. We used a regression model to identify clinical and demographic factors associated with length of time to molecular diagnosis. Kaplan-Meier analysis compared time to diagnosis for the molecular testing era (since 1994) and earlier birth cohorts. The results showed that the median time to molecular diagnosis of the 22q11.2 deletion was 4.7 (range 0-20.7) years. Palatal and cardiac anomalies, but not developmental delay/intellectual disability, were associated with a shorter time to molecular diagnosis. Non-European ethnicity was associated with longer time to diagnosis. Inclusion of a cohort from another 22q11.2DS center increased power to observe a significantly earlier diagnosis for patients born in the molecular testing era. Nonetheless, only a minority were diagnosed in the first year of life. On average, patients were seen in seven (range 2-15) different clinical specialty areas prior to molecular diagnosis. The findings indicate that even for those born in the molecular testing era, individuals with 22q11.2DS and their families face a diagnostic odyssey that is often prolonged, particularly in the absence of typical physical congenital features or for those of non-European ancestry. The results support educational efforts to improve clinical recognition and testing, and ultimately newborn screening as a means of maximizing early detection that would provide the best opportunity to optimize outcomes.
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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 | 0.003 |
| 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 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 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".