WT1 variantes patogênicas germinais impulsionam um espectro de predisposições renais pediátricas: WA...
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| ID | BMA-WT1-GERMLINE-WILMS |
|---|---|
| Tipo | Relevância terapêutica |
| Estado | reviewed 2026-05-18 | pending_clinical_signoff | actionability review required |
| Doenças | DIS-WILMS |
| Fontes | SRC-NCCN-PEDIATRIC-SARCOMA |
Fatos de ação
| Biomarcador | BIO-WT1-GERMLINE |
|---|---|
| Variante | Patogênica da linha germinativa WT1 (WAGR / Síndromes de Denys-Drash / Frasier) |
| Doença | DIS-WILMS |
| Nível ESCAT | IIA |
| Combinações recomendadas | ecografia renal a cada 3-4 meses desde o diagnóstico até os 7-8 anos, análise de urina + pressão arterial em cada visita (vigilância glomerular de Denys-Drash), clínica multidisciplinar: oncologia pediátrica + nefrologia + endocrinologia + genética, gonadectomia profilática na síndrome de Frasier (46,XY) — prevenção de gonadoblastoma, monitoramento da função renal + proteinúria (denys -Drach esclerose mesangial difusa frequentemente apresenta na infância), protocolos de COG/SIOP-RTSG Wilms para qualquer nefroblastomade detectado |
| Resumo das provas | WT1 germline pathogenic variants drive a spectrum of pediatric kidney predispositions: WAGR syndrome (11p13 contiguous-gene deletion — Wilms tumor, aniridia, genitourinary anomalies, range of intellectual disability; Wilms risk ~30-50%), Denys-Drash syndrome (missense in zinc- finger domain — pseudohermaphroditism + diffuse mesangial sclerosis + Wilms tumor; risk ~50-90%), and Frasier syndrome (intron-9 splice variants — 46,XY gonadal dysgenesis + focal segmental glomerulosclerosis; gonadoblastoma risk). Confirmed-carrier surveillance protocol (per International Society of Paediatric Oncology / SIOP-RTSG + COG Renal Tumor Committee Consensus / Kalish et al. 2017): renal ultrasound every 3 months from diagnosis through age 7-8 (Wilms incidence peaks before age 5 and falls steeply after age 7), urinalysis at each visit, blood pressure monitoring. Multi-disciplinary involvement: pediatric oncology + nephrology (renal function + proteinuria) + endocrinology (gonadal dysgenesis management) + genetics. Prophylactic gonadectomy is recommended in Frasier syndrome to prevent gonadoblastoma.... |
Notas
STUB — Wave A+B germline expansion. Linked Indication: none (no WT1- specific Indication exists yet). Two-Clinical-Co-Lead signoff queued. Surveillance is age-bounded: cadence drops markedly after age 7-8 when Wilms incidence falls. Variant location largely predicts syndrome subtype: contiguous-gene deletions → WAGR; zinc-finger missense → Denys- Drash; intron-9 splice variants → Frasier. Other 11p13 contiguous-gene deletion phenotypes (e.g. simultaneous involvement of PAX6) explain aniridia and warrant ophthalmology follow-up.
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