Definition
- A rare genetic disorder caused by deletions on chromosome 11p13, affecting genes such as WT1 (tumor suppressor) and PAX6 (eye development).
- The name WAGR comes from its core features:
- W → Wilms tumor (childhood kidney cancer)
- A → Aniridia (partial or complete absence of iris)
- G → Genitourinary anomalies (cryptorchidism, hypospadias, gonadal dysgenesis)
- R → Intellectual disability (mental Retardation)
Pathophysiology
- WT1 gene mutation/deletion → predisposes to nephroblastoma (Wilms tumor).
- PAX6 mutation → responsible for aniridia.
- Larger deletions may include other genes → broader developmental issues.
Clinical Features
- Wilms tumor risk ~45–60% (usually before age 8).
- Aniridia → poor vision, photophobia, risk of glaucoma/cataracts.
- Genitourinary anomalies → ambiguous genitalia, infertility risk, gonadoblastoma risk.
- Developmental delay/intellectual disability (variable severity).
- May also present with obesity, autism spectrum features, or kidney failure later in life.
Oncology Relevance
- Wilms tumor (nephroblastoma) is the most serious risk → requires early and regular screening (renal ultrasounds every 3 months until ~8 years of age).
- Multimodal therapy (surgery + chemotherapy ± radiotherapy) if tumor develops.
Pharmacist’s Role
- Be aware of the genetic–oncology link (WT1 deletion → Wilms tumor risk).
- Support chemotherapy regimens for nephroblastoma (e.g., actinomycin D, vincristine, doxorubicin).
- Monitor for drug toxicities:
- Actinomycin D → hepatotoxicity, myelosuppression
- Vincristine → neurotoxicity, constipation
- Doxorubicin → cardiotoxicity
- Supportive care: antiemetics, infection prophylaxis, long-term monitoring.
- Counsel families about lifelong surveillance of kidney and eye health.
Key Point for Oncology Pharmacists:
WAGR syndrome is a genetic cancer predisposition syndrome where the presence of aniridia in a child is a red flag for possible Wilms tumor, requiring active monitoring and early intervention.