Confirmed germline pathogenic / likely-pathogenic variant in TSC1 (hamartin) or TSC2 (tub...

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

ID	`RF-TSC-CONFIRMED-CARRIER`
Тип	Тривожна ознака
Статус	переглянуто 2026-05-20 \| очікує клінічного підпису
Хвороби	`DIS-LAM` `DIS-RCC`
Джерела	`SRC-NCCN-CNS-2025` `SRC-NCCN-KIDNEY-2025`

Походження тривожної ознаки

Визначення	Confirmed germline pathogenic / likely-pathogenic variant in TSC1 (hamartin) or TSC2 (tuberin) — Tuberous Sclerosis Complex (TSC). Patient has had germline panel testing returned positive, OR meets clinical diagnostic criteria per International TSC Consensus 2012 / 2021 (≥2 major features OR 1 major + ≥2 minor features). Autosomal- dominant multi-organ hamartoma syndrome — mTOR pathway hyperactivation drives benign tumors in essentially every organ system: cortical / subependymal tubers + subependymal giant cell astrocytoma (SEGA) + cardiac rhabdomyoma (infants) + facial angiofibromas + shagreen patch + ungual fibromas + dental enamel pits + retinal hamartomas + renal angiomyolipoma (AML, ~80% lifetime) + lymphangioleiomyomatosis (LAM, adult women) + neurocognitive / epileptic phenotype (TSC- Associated Neuropsychiatric Disorders, TAND). Malignant transformation is rare but cancer is re...
Клінічний напрям	investigate
Категорія	other

Логіка спрацьовування

{
  "any_of": [
    {
      "finding": "germline_tsc1_pathogenic_variant_confirmed",
      "value": true
    },
    {
      "finding": "germline_tsc2_pathogenic_variant_confirmed",
      "value": true
    },
    {
      "finding": "tuberous_sclerosis_clinical_diagnostic_criteria_met",
      "value": true
    }
  ],
  "type": "lab_value"
}

Нотатки

Wave O confirmed-carrier surveillance pathway — Tuberous Sclerosis Complex (TSC / TSC1 / TSC2). Fires on documented germline TSC1 / TSC2 pathogenic variant positivity OR clinical-diagnostic criteria met per International TSC Consensus 2012 / 2021. Engine routes to PreventionPlan recommending: (a) IND-TSC-CARRIER-SURVEILLANCE (standard) — International TSC Consensus 2021 protocol: brain MRI q1-3y from infancy to age 25, then symptom-driven (SEGA detection); renal MRI / contrast US q1-3y from infancy (renal AML + RCC); cardiac echo in infancy (rhabdomyoma — usually involutes; surveillance into adulthood only if persistent); pulmonary function testing + chest HRCT baseline at age 18 in females (LAM screening); dermatologic exam q1y; ophthalmologic exam q1-3y (retinal hamartomas); neuropsychiatric screening q1y (TAND); dental exam q6mo. (b) IND-TSC-CARRIER-INTENSIFIED (aggressive) — standard PLUS proactive mTOR inhibitor (everolimus or sirolimus) initiation for renal AML > 3 cm or growing, AND for SEGA showing growth on serial MRI (replaces / delays surgical resection in many cases); intensified LAM management in adult women. STUB pending two-Clinical-Co-Lead signoff per CHARTER §6.1...

Де використовується

Indications

IND-TSC-CARRIER-INTENSIFIED - IND-TSC-CARRIER-INTENSIFIED
IND-TSC-CARRIER-SURVEILLANCE - IND-TSC-CARRIER-SURVEILLANCE