Myotonic dystrophy type 1 evaluation from a generation and CTG repeat expansion perspective
Bibliographic record
Abstract
Abstract Background Myotonic dystrophy type 1 (DM1) is an autosomal dominant neuromuscular and multisystem disorder with variable expressivity, caused by an unstable CTG repeat expansion in DMPK gene, that tends to increase continuously over an individual's lifetime and in successive generations (anticipation phenomenon). Cardiac manifestations are considered a major contributor to morbidity and premature death in DM1. However, neither genetics not generation data are considered for risk stratification in current guidelines. This study sought to evaluate the cardiac conduction abnormalities in a large cohort of DM1 patients from this perspective. Methods This is a multicenter retrospective study, we evaluate cardiac involvement throughout life, assessing the influence of age at diagnosis (first group : diagnosed older than >59 years old, second form 40-59, third younger group <40), generational differences (1st generation born from 102-1965; 2nd, from 1966 to 1990; and 3rd generation 1991 to 2015), and the number of CTG repeats on disease progression. The primary endpoint was a composite of adverse cardiovascular events, which included cardiac conduction abnormalities (CCA) development over the lifetime, device implantation (PM and/or ICD), major ventricular arrhythmias (MVA), and/or cardiogenic syncope. Cardiac Conduction Abnormalities (CCAs) were considered when at least one of the following features was present: 1) first-degree atrioventricular block (AVB-I) defined by PR interval of 200 msec plus QRS duration of 120 msec or more, including right and left bundle branch blocks (R-BBB, L-BBB).; 2) HV interval longer than 70 msec in electrophysiological evaluation; 3) second-degree or third-degree atrioventricular block (AVB-II or AVB-III). Results 549 DM1 patients from 16 Spanish hospitals were evaluated (48.1 % women, mean age at diagnosis 33.6 (±16.2) years old). During follow-up, the primary composite endpoint was present in 182 (33.15%) patients. When we compared to the first older group (≥ 60 years old), the risk of the primary endpoint in the third younger group is 4.7–fold higher (HR: 4.70 CI95%: 2.4-9.1; p<0.001) and 2.4-fold higher (HR: 2.42 CI95%: 1.2-4.7; p=0.008) for the second group. Similarly, higher risks of the primary endpoint were found in the youngest generation (35 times more frequent in the 3rd generation compared with the 1st generation) and increased with CTG repeat expansion. Conclusion . We identified an earlier onset of electrical disturbances in those patients diagnosed at a younger age, in successive generations and in groups with longer repeat expansions This is supported by the anticipation phenomenon. This data may help future guidelines for risk stratification in DM1 patients.
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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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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) | 0.001 | 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".