OR08-05 Case Series Of French Canadian Patients With Paragangliomas Carrying The c.397C>T SDHC Mutation: Insights On SDHC Phenotype And Outcomes
Bibliographic record
Abstract
Abstract Disclosure: S. Parisien-La Salle: None. D. Nadine: None. Z. El-Haffaf: None. A. Lacroix: None. A. Gimenez-Roqueplo: None. I. Bourdeau: None. Introduction: Germline SDHC pathogenic variants in pheochromocytomas and paragangliomas (PGLs) (PPGLs) are rare with a prevalence of 1-2% (1). The associated phenotype of patients with SDHC mutated PPGLs remains unclear. Objective: Describe the phenotype and outcomes of our cohort of patients with PGL carrying the recurrent SDHC c.397C>T (p.Arg133Ter) mutation due to a likely French Canadian founder effect (2). Methods: We retrospectively reviewed the charts of patients with SDHC related PPGLs from 2005-2022 to analyse their phenotype and outcomes. Results: In our genotyped PPGL cohort, 35% (84/240) of patients had an identified germline pathogenic/likely pathogenic variant in a known PPGL susceptibility gene. Of these, 27.4% (23/84) had a mutation in the SDHC gene. The SDHC c.397C>T mutation was identified in 87% (20/23) of SDHC patients, all being French Canadians. In the SDHC c.397C>T group, mean age at diagnosis was 46.3 years old. Sixty-five percent (13/20) presented with head and neck PGLs (HNPGL) and 35% (7/20) with thoraco-abdominal PGLs (TAPGLs), with 2 being intracardiac and one retrocardiac PGLs. There were no pheochromocytomas. Fifteen percent (3/20) had metastatic disease and 20% (4/20) had multiple tumors. One patient also presented with a GIST. TAPGLs were functional in 85.7% (6/7) of cases (mostly norepinephine/normetanephrine) and HNPGLs were biochemically active in 38.5% (5/13) of cases (mostly dopamine). In these 20 SDHC c.397C>T mutated patients with PGLs, 12 underwent curative surgery and were considered in remission. The PGL recurrence rate was of 25% (3/12) during a mean follow-up time of 11.4 years. The other 3 patients were not of French Canadian origin and had pathogenic variants that had previously been described: SDHC c.487T>C (p.Ser163Pro), SDHC c.380 A>G (p.His127Arg) and SDHC c.1A>G (p.Met1Val). Conclusion: The SDHC c.397C>T mutation is very prevalent in patients with PGLs who are of French Canadian descent due to a likely founder effect. Compared to other SDHC cohorts, SDHC c.397C>T PGLs showed a lower rate of metastasis and associated tumors, but a higher rate of multiple PGLs. Although this may indicate a possibly less aggressive phenotype, the recurrence rate was high at 25%, thus requiring close monitoring and lifelong follow-up. Bibliography: 1. Toledo RA, Burnichon N, Cascon A, Benn DE, Bayley JP, Welander J, et al. Consensus Statement on next-generation-sequencing-based diagnostic testing of hereditary phaeochromocytomas and paragangliomas. Nat Rev Endocrinol. 2017;13(4):233-47.2. Bourdeau I, Grunenwald S, Burnichon N, Khalifa E, Dumas N, Binet MC, et al. A SDHC Founder Mutation Causes Paragangliomas (PGLs) in the French Canadians: New Insights on the SDHC-Related PGL. J Clin Endocrinol Metab. 2016;101(12):4710-8. Presentation: Friday, June 16, 2023
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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) | 0.000 | 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".