Confirmed biallelic germline pathogenic / likely-pathogenic variants in RECQL4 (RecQ-like...

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

ID	`RF-ROTHMUND-THOMSON-CONFIRMED-CARRIER`
Type	Red flag
Status	reviewed 2026-05-20 \| pending_clinical_signoff
Diseases	`DIS-BCC` `DIS-OSTEOSARCOMA` `DIS-SOFT-TISSUE-SARCOMA`
Sources	`SRC-NCCN-BONE-SARCOMA` `SRC-NCCN-SKIN-2025`

Red Flag Origin

Definition	Confirmed biallelic germline pathogenic / likely-pathogenic variants in RECQL4 (RecQ-like helicase 4) — Rothmund-Thomson Syndrome (RTS). Patient has had germline RECQL4 testing returned positive in both alleles (autosomal-recessive inheritance), or meets clinical diagnostic criteria (poikiloderma in infancy + sparse / abnormal hair + skeletal anomalies + ± juvenile cataracts). No current personal cancer diagnosis in the carrier being assessed (current cancer diagnosis routes to treatment-track plan with RTS status driving systemic-therapy selection — RECQL4-deficient cells are hypersensitive to ionizing radiation and DNA-damaging chemotherapy / alkylators, with implications for radiotherapy dose modification and avoidance of camptothecin / etoposide-style topoisomerase agents). Lifetime osteosarcoma risk ~30%, plus non-melanoma skin cancer (especially in poikiloderma-affected skin), and...
Clinical direction	investigate
Category	other

Trigger Logic

{
  "any_of": [
    {
      "finding": "germline_recql4_biallelic_pathogenic",
      "value": true
    },
    {
      "finding": "rothmund_thomson_clinical_criteria_met",
      "value": true
    }
  ],
  "type": "lab_value"
}

Notes

Wave O confirmed-carrier surveillance pathway — Rothmund-Thomson Syndrome (RTS / RECQL4). Fires on documented germline RECQL4 biallelic pathogenic variants OR clinical-diagnostic criteria met (poikiloderma + sparse hair + skeletal anomalies). Engine routes to PreventionPlan recommending: (a) IND-ROTHMUND-THOMSON-CARRIER-SURVEILLANCE (standard) — annual skeletal survey (whole-body imaging — plain films + targeted US / MRI as warranted) + immediate X-ray / MRI of any persistent bone pain or palpable mass; dermatologic exam q6-12mo with biopsy of any suspicious lesion (poikiloderma background complicates clinical recognition); ophthalmologic exam annually (juvenile cataracts). (b) IND-ROTHMUND-THOMSON-CARRIER-INTENSIFIED (aggressive) — standard PLUS whole-body MRI q1y (replacing skeletal survey, especially in adolescent peak osteosarcoma years 10-20) + bone-pain symptom-driven low-threshold imaging + bone-tumor specialist co-management. STUB pending two-Clinical-Co-Lead signoff per CHARTER §6.1 dev-mode exemption. Source-set TODO: RTS-specific surveillance source — Wang et al. Cancer 2003; International RTS Registry recommendations; Larizza et al. Orphanet J Rare Dis 2010 — Wave O au...

Used By

Indications

IND-ROTHMUND-THOMSON-CARRIER-INTENSIFIED - IND-ROTHMUND-THOMSON-CARRIER-INTENSIFIED
IND-ROTHMUND-THOMSON-CARRIER-SURVEILLANCE - IND-ROTHMUND-THOMSON-CARRIER-SURVEILLANCE