Wilms Tumor in Children With AMER1/WTX Germline Pathogenic Variants: A Multicenter Case Series

Area of Science:

• Pediatric Oncology
• Cancer Genetics
• Nephrology

Background:

• Wilms tumor (WT) has genetic links, with AMER1 variants being rare but associated with osteopathia striata with cranial sclerosis (OSCS).
• Germline pathogenic variants in AMER1 are less common than somatic mutations in WT.

Purpose of the Study:

• To investigate the role of AMER1 germline variants in pediatric Wilms tumor.
• To characterize the clinical presentation and outcomes of patients with WT and AMER1 variants.

Main Methods:

• A multicenter retrospective case series of patients with AMER1 germline variants and WT.
• Comparison of findings with previously published data on similar cases.

Main Results:

• Four female patients with WT and AMER1 variants were identified; one had a familial variant.
• Tumor stages varied (I-IV), with three requiring adjuvant therapy; bilateral tumors occurred in 20% of combined cases.
• One patient lacked the typical OSCS phenotype, suggesting incomplete penetrance; no recurrences or deaths were reported.

Conclusions:

• AMER1 is a Wilms tumor predisposition gene requiring surveillance.
• Prolonged risk for WT is associated with AMER1 variants, with diagnosis ages ranging up to 12 years.
• Nephron-sparing surgery and familial genetic testing are recommended for children with AMER1 variants and WT.