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

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

ID	`RF-SDHC-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 SDHC (succinate dehydrogenase complex subunit C) — paraganglioma syndrome type 3 (PGL3). SDHC carries a lower lifetime paraganglioma + pheochromocytoma risk (~10-15% by age 60 in pooled international registry data, lower in some kindreds at ~25% aggregate per Andrews et al. JCEM 2018) than SDHB / SDHD, and metastatic disease is rare (<5% of incident events). Tumor distribution is predominantly head + neck parasympathetic paragangliomas — carotid body, jugulo-tympanic, vagal, and skull-base locations — rather than the abdominal / thoracic sympathetic distribution characteristic of SDHB. SDH- deficient gastrointestinal stromal tumor and renal cell carcinoma have been described but are uncommon. Inheritance is autosomal- dominant without the SDHD / SDHAF2 maternal-imprinting pattern (penetrant from either parent). Patient has had...
Клінічний напрям	investigate
Категорія	other

Логіка спрацьовування

{
  "any_of": [
    {
      "finding": "germline_sdhc_specific_carrier",
      "value": true
    },
    {
      "finding": "paraganglioma_pgl3_clinical_criteria_met",
      "value": true
    }
  ],
  "type": "lab_value"
}

Нотатки

Gene-specific paraganglioma syndrome 3 (PGL3) confirmed-carrier RF. Fires on documented germline SDHC pathogenic / likely-pathogenic variant positivity in an asymptomatic individual. Distinct from the multi-gene RF-SDH-CONFIRMED-CARRIER which fires on the legacy `germline_sdhc_pathogenic_variant_confirmed` finding; this RF uses `germline_sdhc_specific_carrier` (or `paraganglioma_pgl3_clinical_ criteria_met`) to avoid double-firing under the new gene-stratified surveillance pathway. Engine routes to PreventionPlan: (a) IND-SDHC-CARRIER-SURVEILLANCE (standard) — head + neck MRI annually from age 10-15 (parasympathetic-predominant); plasma free metanephrines + methoxytyramine q12mo (3-MT critical for dopaminergic biochemistry); abdominal MRI q2-3y for the rare sympathetic PGL + SDH-deficient RCC / GIST; pre-operative alpha-blockade for any secretory PGL resection; cascade testing offered to first-degree relatives. (b) IND-SDHC-CARRIER-SYMPTOM-DRIVEN (aggressive in the rhetorical sense — actually less-intensive symptom-driven track offered as the alternative given SDHC's lower penetrance + low metastatic rate; some referral centers offer biochemistry-only with cross- sectional imaging...

Де використовується

Indications

IND-SDHC-CARRIER-SURVEILLANCE - IND-SDHC-CARRIER-SURVEILLANCE
IND-SDHC-CARRIER-SYMPTOM-DRIVEN - IND-SDHC-CARRIER-SYMPTOM-DRIVEN