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

Background: 10-15% of children with Wilms tumor (WT) have predisposing genetic syndromes. Somatic mutations are frequently identified; however, germline pathogenic variants in AMER1 are much less prevalent and are associated with osteopathia striata with cranial sclerosis (OSCS).

Methods: A multicenter retrospective case series was conducted reviewing patients with AMER1 germline variants and WT from 2012 to 2023. Results were compared with published data from six other children.

Results: Four female children were identified. Age at WT diagnosis ranged from 5 months to 8 years. One patient had familial AMER1 germline variant. Stage of disease ranged from I to IV, and three children required adjuvant therapy. Nephrogenic rests were noted in two patients. Two patients underwent open partial nephrectomy, and two underwent open radical nephrectomy. One patient had mild kidney disease post-resection, and no patients had recurrence or died from disease progression.

Conclusion: Our cohort of four patients, combined with the six patients with WT and AMER1 pathogenic variants previously reported, with 20% (two out of 10) collective incidence of bilateral tumors, support AMER1 as a WT predisposition gene warranting surveillance. Collectively, age of WT diagnosis ranged from 5 months to 12 years, which demonstrates potential for prolonged risk. Pathogenic AMER1 germline variants were previously thought to have 100% penetrance; however, one of four current cases did not exhibit an OSCS phenotype. We report the first documented case of a familial AMER1 germline variant and WT. We conclude that nephron-sparing surgery and familial genetic testing should be considered for children with AMER1 germline variants and WT.