Confirmed germline pathogenic / likely-pathogenic variant in SDHB (succinate dehydrogenas...

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

ID	`RF-SDHB-SPECIFIC-CARRIER`
Тип	Тривожна ознака
Статус	переглянуто 2026-05-20 \| очікує клінічного підпису
Хвороби	`DIS-PHEOCHROMOCYTOMA`
Джерела	`SRC-ENDOCRINE-SOCIETY-MEN-2023` `SRC-NCCN-GENETIC-FAMILIAL-BREAST-OVARIAN-2025` `SRC-NCCN-NET-2025`

Походження тривожної ознаки

Визначення	Confirmed germline pathogenic / likely-pathogenic variant in SDHB (succinate dehydrogenase complex subunit B) — paraganglioma syndrome type 4 (PGL4). SDHB carries the HIGHEST aggregate lifetime paraganglioma + pheochromocytoma risk among the SDHx subunits (~30-50% by age 60, ~50-70% lifetime in some kindreds) AND the highest metastatic / malignant rate (~30-70% of incident PPGL events metastasize, vs <10% in other SDHx subunits). Tumor distribution is predominantly sympathetic abdominal + thoracic paragangliomas (peri- aortic, organ-of-Zuckerkandl) rather than the head + neck parasympathetic distribution characteristic of SDHD / SDHC. Additional risk: SDH-deficient renal cell carcinoma (~14% lifetime, often aggressive type-2-papillary or oncocytic morphology) and SDH-deficient gastrointestinal stromal tumor. Pediatric onset is documented — index PPGL events before age 10 occur in ~10% o...
Клінічний напрям	investigate
Категорія	other

Логіка спрацьовування

{
  "any_of": [
    {
      "finding": "germline_sdhb_specific_carrier",
      "value": true
    },
    {
      "finding": "paraganglioma_pgl4_clinical_criteria_met",
      "value": true
    }
  ],
  "type": "lab_value"
}

Нотатки

Gene-specific paraganglioma syndrome 4 (PGL4) confirmed-carrier RF — CRITICAL severity. Fires on documented germline SDHB pathogenic / likely-pathogenic variant positivity in an asymptomatic individual. Distinct from the multi-gene RF-SDH-CONFIRMED-CARRIER which fires on the legacy `germline_sdhb_pathogenic_variant_confirmed` finding; this RF uses `germline_sdhb_specific_carrier` (or `paraganglioma_pgl4_ clinical_criteria_met`) to avoid double-firing under the new gene- stratified surveillance pathway. Engine routes to PreventionPlan: (a) IND-SDHB-CARRIER-SURVEILLANCE (standard) — whole-body MRI annually from age 6-10 (younger if family-specific proband younger); plasma free metanephrines + methoxytyramine (3-MT) q6-12mo; head + neck MRI q2-3y; abdominal MRI annually for sympathetic PGL + RCC + GIST; 68Ga-DOTATATE PET reserved for staging confirmed lesions (high SSTR2 expression in SDHx-PPGL); 18F-FDG PET as alternative functional modality (SDHB-PPGL high FDG-avidity reported); pre-operative alpha-blockade mandatory for any PPGL resection; cascade testing. (b) IND-SDHB-CARRIER-INTENSIFIED (aggressive) — earlier baseline (age 5 in pediatric-onset kindreds) + q6mo biochemistry + fun...

Де використовується

Indications

IND-SDHB-CARRIER-INTENSIFIED - IND-SDHB-CARRIER-INTENSIFIED
IND-SDHB-CARRIER-SURVEILLANCE - IND-SDHB-CARRIER-SURVEILLANCE