Double heterozygous pathogenic variants in BRCA2 and CHEK2 in a girl with adrenocortical carcinoma

Pediatric adrenocortical tumors (pACTs) are rare endocrine neoplasms with variable prognosis, commonly associated with germline pathogenic variants (PVs) in the tumor suppressor gene TP53. Here, we report the case of a 3.1-year-old female presenting with virilization and Cushing syndrome due to a left-sided adrenal mass. The tumor was completely resected and confirmed as stage II adrenocortical carcinoma (ACC) based on the Wieneke index. Comprehensive molecular profiling revealed heterozygous germline PVs in BRCA2 [c.9382C>T p.(Arg3128*)] and CHEK2 [c.1232G>A p.(Trp411*)]. These findings suggest a potential role of impaired DNA damage repair in ACC pathogenesis, as both PVs are associated with hereditary breast and ovarian cancer (HBOC) syndromes and genomic instability. This case expands the genetic spectrum of pACT and underscores the importance of advanced molecular analyses in identifying rare germline alterations that may inform personalized treatment strategies and cancer prevention programs. Although no additional treatment was required in this case, BRCA2 status highlights the potential for tailored therapeutic approaches, including poly(ADP-ribose) polymerase (PARP) inhibitors, in selected patients. Further research is warranted to explore the specific contributions of BRCA2 and CHEK2 PVs to ACC tumorigenesis and their implic ations for targeted therapies.