WT1 germline pathogenic variants drive a spectrum of pediatric kidney predispositions: WA...
Детермінований перегляд YAML-сутності з джерельної бази. Клінічний авторитет лишається за вказаними source ID та статусом клінічного sign-off.
| ID | BMA-WT1-GERMLINE-WILMS |
|---|---|
| Тип | Клінічна застосовність |
| Статус | переглянуто 2026-05-18 | очікує клінічного підпису | потрібне рев’ю клінічної застосовності |
| Хвороби | DIS-WILMS |
| Джерела | SRC-NCCN-PEDIATRIC-SARCOMA |
Дані про клінічну застосовність
| Біомаркер | BIO-WT1-GERMLINE |
|---|---|
| Варіант | WT1 germline pathogenic (WAGR / Denys-Drash / Frasier syndromes) |
| Хвороба | DIS-WILMS |
| Рівень ESCAT | IIA |
| Рекомендовані комбінації | renal ultrasound every 3-4 months from diagnosis through age 7-8, urinalysis + blood pressure at each visit (Denys-Drash glomerular surveillance), multi-disciplinary clinic: pediatric oncology + nephrology + endocrinology + genetics, prophylactic gonadectomy in Frasier syndrome (46,XY) — gonadoblastoma prevention, renal function monitoring + proteinuria (Denys-Drash diffuse mesangial sclerosis often presents in infancy), COG / SIOP-RTSG Wilms protocols for any detected nephroblastoma |
| Підсумок доказів | 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.... |
Нотатки
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.
Де використовується
У YAML-корпусі не знайдено зворотних посилань.