Confirmed biallelic germline pathogenic / likely-pathogenic variants in WRN (RECQL2; Wern...

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

ID	`RF-WERNER-CONFIRMED-CARRIER`
Тип	Тривожна ознака
Статус	переглянуто 2026-05-20 \| очікує клінічного підпису
Хвороби	`DIS-MELANOMA` `DIS-MENINGIOMA` `DIS-OSTEOSARCOMA` `DIS-SOFT-TISSUE-SARCOMA` `DIS-THYROID-ANAPLASTIC` `DIS-THYROID-PAPILLARY`
Джерела	`SRC-NCCN-CNS-2025` `SRC-NCCN-MELANOMA-2025` `SRC-NCCN-STS-2025` `SRC-NCCN-THYROID-2025`

Походження тривожної ознаки

Визначення	Confirmed biallelic germline pathogenic / likely-pathogenic variants in WRN (RECQL2; Werner syndrome RecQ-like helicase) — Werner Syndrome (adult progeria). Patient has had germline WRN testing returned positive in both alleles (autosomal-recessive inheritance), or meets clinical diagnostic criteria (cardinal features all present: bilateral cataracts, sclerodermatous skin changes, characteristic facies — bird-like, short stature; plus ≥2 minor signs: gray hair / alopecia, type-2 diabetes, hypogonadism, osteoporosis, abnormal voice, flat feet — typically manifest in late adolescence / 20s). No current personal cancer diagnosis in the carrier being assessed. Werner syndrome is a premature-aging segmental progeroid syndrome with a distinctive cancer spectrum dominated by soft-tissue sarcoma, osteosarcoma, melanoma (acral / mucosal subtypes over-represented), meningioma, thyroid follicular...
Клінічний напрям	investigate
Категорія	other

Логіка спрацьовування

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

Нотатки

Wave O confirmed-carrier surveillance pathway — Werner Syndrome (WRN / RECQL2). Fires on documented germline WRN biallelic pathogenic variants OR clinical-diagnostic criteria met. Engine routes to PreventionPlan recommending: (a) IND-WERNER-CARRIER-SURVEILLANCE (standard) — annual full-body skin exam by dermatologist (melanoma — acral / mucosal subtypes over-represented; sclerodermatous skin complicates recognition); annual thyroid US (follicular / anaplastic enrichment); cardiac risk-factor surveillance (premature atherosclerosis is a defining Werner feature — annual lipid panel, BP, glycemia, echo q3-5y); skeletal pain-driven imaging (low threshold for X-ray / MRI on any persistent musculoskeletal pain). Cancer- screening colonoscopy + mammography per general-population guidelines (no Werner-specific elevation of these cancers). (b) IND-WERNER-CARRIER-INTENSIFIED (aggressive) — standard PLUS whole-body MRI baseline + q2-3y (full-body screening given diverse cancer spectrum) + intensified cardiovascular workup (statin + glycemic control for premature atherosclerosis) + bone-density q2y monitoring with bisphosphonate consideration for premature osteoporosis. STUB pending two-Clini...

Де використовується

Indications

IND-WERNER-CARRIER-INTENSIFIED - IND-WERNER-CARRIER-INTENSIFIED
IND-WERNER-CARRIER-SURVEILLANCE - IND-WERNER-CARRIER-SURVEILLANCE