Confirmed biallelic germline pathogenic / likely-pathogenic variants in a mismatch repair...

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

ID	`RF-CMMRD-CONFIRMED-CARRIER`
Тип	Тривожна ознака
Статус	переглянуто 2026-05-19 \| очікує клінічного підпису
Хвороби	`DIS-CRC` `DIS-GLIOMA-LOW-GRADE`
Джерела	`SRC-ASCO-ACMG-LYNCH-2014` `SRC-NCCN-GENETIC-FAMILIAL-CRC-2025` `SRC-TABORI-CMMRD-2017` `SRC-WIMMER-CMMRD-2014`

Походження тривожної ознаки

Визначення	Confirmed biallelic germline pathogenic / likely-pathogenic variants in a mismatch repair (MMR) gene — MLH1, MSH2, MSH6, or PMS2 — defining Constitutional Mismatch Repair Deficiency (CMMRD) syndrome. Rare (~1 in 1,000,000) but severely cancer-predisposing autosomal-recessive syndrome in pediatric and adolescent patients. Lifetime cancer risk approaches 100% by adolescence; first malignancy typically before age 18, often within first decade. Cancer spectrum: hematologic (non-Hodgkin lymphoma, leukemia — often before age 10), CNS (medulloblastoma, glioblastoma, supratentorial PNET — often age 5-15), gastrointestinal (early-onset CRC + small bowel adenoma — often age 10-25 with Lynch-like phenotype but more aggressive), others (sarcoma, Wilms, pediatric Cushing, NF1-like phenotype including café-au-lait macules). Café-au-lait spots in a young cancer patient should always prompt CMMRD consi...
Клінічний напрям	investigate
Категорія	other

Логіка спрацьовування

{
  "any_of": [
    {
      "finding": "germline_cmmrd_biallelic_mmr_confirmed",
      "value": true
    },
    {
      "finding": "cmmrd_clinical_criteria_met",
      "value": true
    },
    {
      "finding": "biallelic_pms2_pathogenic_confirmed",
      "value": true
    },
    {
      "finding": "biallelic_mlh1_pathogenic_confirmed",
      "value": true
    },
    {
      "finding": "biallelic_msh2_pathogenic_confirmed",
      "value": true
    },
    {
      "finding": "biallelic_msh6_pathogenic_confirmed",
      "value": true
    }
  ],
  "type": "lab_value"
}

Нотатки

Prevention-persona RedFlag for CMMRD confirmed-carrier pediatric cohort. Surveillance per Care for CMMRD (C4CMMRD) consortium 2014: whole-body MRI annually from diagnosis; brain MRI q6mo from age 2; colonoscopy q6mo from age 6; upper GI endoscopy + small-bowel capsule annual from age 8; CBC + serum protein electrophoresis + abdominal US q6mo. Cascade testing of siblings + parental MMR carrier confirmation. Immunotherapy (anti-PD-1) effective in established CMMRD-related cancers (Bouffet 2016, Larkin/CheckMate series). STUB pending two-Co-Lead signoff per CHARTER §6.1 dev-mode.

Де використовується

Indications

IND-CMMRD-CARRIER-PREVENTION-OBSERVATION - IND-CMMRD-CARRIER-PREVENTION-OBSERVATION
IND-CMMRD-CARRIER-PREVENTION-SURVEILLANCE - IND-CMMRD-CARRIER-PREVENTION-SURVEILLANCE