Confirmed germline pathogenic / likely-pathogenic variant in SMAD4 or BMPR1A — Juvenile P...

Детермінований перегляд YAML-сутності з джерельної бази. Клінічний авторитет лишається за вказаними source ID та статусом клінічного sign-off.

ID	`RF-JPS-CONFIRMED-CARRIER`
Тип	Тривожна ознака
Статус	переглянуто 2026-05-20 \| очікує клінічного підпису
Хвороби	`DIS-CRC` `DIS-GASTRIC` `DIS-PDAC`
Джерела	`SRC-ESMO-CRC-2024` `SRC-NCCN-COLON-2025` `SRC-NCCN-GENETIC-FAMILIAL-CRC-2025`

Походження тривожної ознаки

Визначення	Confirmed germline pathogenic / likely-pathogenic variant in SMAD4 or BMPR1A — Juvenile Polyposis Syndrome (JPS). Patient has had germline panel testing returned positive (or, in the SMAD4 / BMPR1A-negative ~20% of clinically diagnosed JPS, meets clinical diagnostic criteria: ≥5 juvenile polyps in colorectum, juvenile polyps throughout the GI tract, or any number of juvenile polyps with a JPS family history). Autosomal-dominant hamartomatous polyposis distinct from FAP (adenomatous) and PJS (hamartomatous-STK11) — JPS polyps are juvenile- type (mucus-filled lamina propria, smooth surface) with malignant potential through retention-polyp → mixed → adenomatous → carcinoma pathway. Lifetime CRC risk ~40%, gastric ~21%, small bowel + pancreatic modest. SMAD4 carriers have a distinct ~22% overlap with Hereditary Hemorrhagic Telangiectasia (HHT, Osler-Weber-Rendu) requiring cardiovascular AVM...
Клінічний напрям	investigate
Категорія	other

Логіка спрацьовування

{
  "any_of": [
    {
      "finding": "germline_smad4_pathogenic_variant_confirmed",
      "value": true
    },
    {
      "finding": "germline_bmpr1a_pathogenic_variant_confirmed",
      "value": true
    },
    {
      "finding": "jps_clinical_diagnostic_criteria_met",
      "value": true
    }
  ],
  "type": "lab_value"
}

Нотатки

Wave O confirmed-carrier surveillance pathway — Juvenile Polyposis Syndrome (JPS / SMAD4 / BMPR1A). Fires on documented germline SMAD4 / BMPR1A pathogenic variant positivity OR clinical-diagnostic criteria met in SMAD4 / BMPR1A-negative phenotypic JPS. Engine routes to PreventionPlan recommending: (a) IND-JPS-CARRIER-SURVEILLANCE (standard) — colonoscopy q1-3y from age 12-15 (intensified to every 6 months once polyps appear); upper endoscopy q1-3y from age 15 (intensified once polyps appear); juvenile-polyp-burden-driven prophylactic colectomy decision; SMAD4-specific HHT screening at diagnosis (pulse oximetry, contrast echocardiography for pulmonary AVMs, brain MRI for cerebral AVMs). (b) IND-JPS-CARRIER-INTENSIFIED (aggressive) — standard PLUS earlier prophylactic colectomy discussion for polyp-burden patients (juvenile-polyp count rapidly exceeding endoscopic-clearance capacity) + intensified SMAD4-HHT AVM management discussion. STUB pending two-Clinical-Co-Lead signoff per CHARTER §6.1 dev-mode exemption. Lifetime cancer risk in confirmed SMAD4 / BMPR1A carriers (NCCN Genetic Familial High-Risk: Colorectal v2.2025; Brosens et al. Gut 2007): - Colorectal: ~40% lifetime (range 1...

Де використовується

Indications

IND-JPS-CARRIER-INTENSIFIED - IND-JPS-CARRIER-INTENSIFIED
IND-JPS-CARRIER-SURVEILLANCE - IND-JPS-CARRIER-SURVEILLANCE