Constitutional Mismatch Repair Deficiency: Scoping Review of a Cancer‐Predisposition Syndrome With Distinctive Cutaneous Findings
Bibliographic record
Abstract
Constitutional mismatch repair deficiency (CMMRD) is a rare but severe hereditary cancer predisposition syndrome caused by biallelic pathogenic variants in one of the mismatch repair genes (MLH1, MSH2, MSH6, or PMS2). The condition mainly presents in childhood, with cancers primarily affecting the hematological, brain, and gastrointestinal systems, along with cutaneous features typical of neurofibromatosis type 1. This scoping review aims to explore the clinical characteristics of CMMRD. A systematic search of medical databases resulted in the inclusion of 127 articles. PMS2 is the most affected gene, followed by MSH6, MLH1, and MSH2. Blood and brain malignancies occur in early childhood for all genetic variants, with the age of onset progressively decreasing from PMS2 to MSH6, to MLH1 and MSH2. Gastrointestinal tumors typically present in late adolescence in individuals with PMS2 variants, at slightly younger ages in those with MSH6 variants, and are rarely reported in MLH1 and MSH2 cases. Patients with CMMRD present with café-au-lait macules that are fewer in number and larger than in patients with neurofibromatosis type 1. Additional dermatological findings include hypopigmented patches and intertriginous freckling. PMS2 and MSH6 pathogenic variants are linked to the broadest spectrum of cutaneous manifestations, including vascular tumors, various nevi, and pilomatricomas. Despite its rarity and diverse clinical manifestations, advancements in diagnostic criteria, genetic testing, and surveillance protocols have significantly improved survival rates and cancer management in CMMRD 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 | 0.002 | 0.013 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.003 |
| Bibliometrics | 0.016 | 0.018 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
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".