Patient has a confirmed germline HRAS pathogenic variant — Costello syndrome (CS), an aut...

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

ID	`RF-COSTELLO-CONFIRMED-CARRIER`
Type	Red flag
Status	reviewed 2026-05-19 \| pending_clinical_signoff
Diseases	`DIS-SOFT-TISSUE-SARCOMA`
Sources	`SRC-ESMO-SARCOMA-2024` `SRC-NCCN-BLADDER-2025` `SRC-NCCN-GENETIC-FAMILIAL-BREAST-OVARIAN-2025`

Red Flag Origin

Definition	Patient has a confirmed germline HRAS pathogenic variant — Costello syndrome (CS), an autosomal-dominant RASopathy. CS confers an estimated 6-15% lifetime malignancy risk concentrated in pediatric embryonal sarcomas: embryonal rhabdomyosarcoma (often before age 10, the most common malignancy), neuroblastoma, and adolescent/adult bladder transitional cell carcinoma. Cardiac comorbidity (hypertrophic cardiomyopathy, arrhythmias) is the leading cause of non-cancer mortality. Prevention-persona confirmed-carrier RedFlag (§20).
Clinical direction	investigate
Category	other

Trigger Logic

{
  "any_of": [
    {
      "finding": "germline_hras_pathogenic_confirmed",
      "value": true
    }
  ],
  "type": "lab_value"
}

Notes

Prevention-persona Costello syndrome confirmed-carrier RedFlag (pediatric cancer predisposition Wave M). Engine routes to PreventionPlan for embryonal-sarcoma surveillance: abdominal/pelvic US q3-6mo through age 8-10, then urine cytology + bladder US from age 10 lifelong. Cardiac surveillance is comorbidity-driven and handled by paired cardiology pathway, not this RF. STUB pending two-Clinical-Co-Lead signoff per CHARTER §6.1 dev-mode. Disease anchor DIS-SOFT-TISSUE-SARCOMA covers embryonal RMS; neuroblastoma + bladder TCC cancer-spectrum noted in rationale of paired Indications.

Used By

Indications

IND-COSTELLO-CARRIER-INTENSIFIED - IND-COSTELLO-CARRIER-INTENSIFIED
IND-COSTELLO-CARRIER-SURVEILLANCE - IND-COSTELLO-CARRIER-SURVEILLANCE