Confirmed germline pathogenic / likely-pathogenic variant in one of the SDHx genes — SDHB...

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

ID	`RF-SDH-CONFIRMED-CARRIER`
Type	Red flag
Status	reviewed 2026-05-18 \| pending_clinical_signoff
Diseases	`DIS-PHEOCHROMOCYTOMA` `DIS-RCC`
Sources	`SRC-NCCN-BCELL-2025`

Red Flag Origin

Definition	Confirmed germline pathogenic / likely-pathogenic variant in one of the SDHx genes — SDHB, SDHD, SDHC, SDHA, or SDHAF2 (succinate dehydrogenase complex deficiency syndromes). Patient has had germline SDHx testing returned positive; the pedigree-suspicion question is settled. No current personal cancer diagnosis in the carrier being assessed. Mandates structured multi-organ surveillance with risk stratification by SDHx subunit: SDHB > SDHD > SDHC > SDHA risk gradient, plus the autosomal-dominant paternal-inheritance / maternal- imprinting pattern unique to SDHD and SDHAF2 (only paternally inherited variants are penetrant). Tumor spectrum: pheochromocytoma + paraganglioma (sympathetic abdominal and parasympathetic head/neck) + SDH-deficient RCC (often aggressive type-2-papillary morphology) + SDH-deficient GIST. SDHB pediatric onset and aggressive paraganglioma-pheochromocytoma + RCC burd...
Clinical direction	investigate
Category	other

Trigger Logic

{
  "any_of": [
    {
      "finding": "germline_sdhb_pathogenic_variant_confirmed",
      "value": true
    },
    {
      "finding": "germline_sdhc_pathogenic_variant_confirmed",
      "value": true
    },
    {
      "finding": "germline_sdhd_pathogenic_variant_confirmed",
      "value": true
    },
    {
      "finding": "germline_sdha_pathogenic_variant_confirmed",
      "value": true
    },
    {
      "finding": "germline_sdhaf2_pathogenic_variant_confirmed",
      "value": true
    }
  ],
  "type": "lab_value"
}

Notes

v0.2-B confirmed-carrier surveillance pathway — SDH-deficiency syndromes. Fires on documented germline SDHB / SDHC / SDHD / SDHA / SDHAF2 pathogenic variant positivity in an asymptomatic individual. Engine routes to PreventionPlan recommending: (a) IND-SDH-CARRIER-SURVEILLANCE (standard) — annual whole-body MRI from age 6-10 in SDHB carriers (highest risk); annual plasma free metanephrines + methoxytyramine (3-MT — preferred for SDHx-associated parasympathetic / dopaminergic paragangliomas); head + neck MRI q2-3y for parasympathetic paragangliomas; abdominal MRI for sympathetic paraganglioma + SDH-deficient RCC + GIST; risk gradient SDHB > SDHD > SDHC > SDHA; paternal- inheritance imprinting pattern for SDHD / SDHAF2. (b) IND-SDH-CARRIER-INTENSIFIED (aggressive) — standard PLUS earlier baseline (age 5 in SDHB pediatric kindreds) + closer interval (q6mo biochemistry in highest-risk subset) + functional imaging (68Ga-DOTATATE PET) for staging confirmed lesions. STUB pending two-Clinical-Co-Lead signoff per CHARTER §6.1 dev-mode exemption. Source-set TODO: dedicated SDH-deficiency syndromes source — International Pheochromocytoma / Paraganglioma Endocrine Society Guideline (Lenders e...

Used By

Indications

IND-SDH-CARRIER-INTENSIFIED - IND-SDH-CARRIER-INTENSIFIED
IND-SDH-CARRIER-SURVEILLANCE - IND-SDH-CARRIER-SURVEILLANCE