Pediatric gastrointestinal stromal tumor: Report of two novel patients harboring germline variants in SDHB and SDHC genes

•Multi-gene hereditary cancer testing detected two loss-of-function variants, in SDHB and SDHC genes in two patients with pediatric gastric GIST; one of these variants has never been reported.•Both variants, detected in heterozygous status in the DNA isolated from blood, were found in the tumor DNA sample with an allele burden greater than 95%, suggesting a loss-of-heterozygosity in the cancer cells.•The identification of constitutional SDH deficiency by the molecular test is critical to direct genetic counseling and take preventive and surveillance measures not only for patients but also for other mutation carriers in the family. Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract and rarely occur in pediatric patients. 85% of pediatric GISTs and 15% of adult GISTs lack of KIT or PDGFRA mutations. 40% of these “wild-type” GISTs present loss of function mutations in genes encoding for the subunits of the succinate dehydrogenase (SDH) complex. Germline mutations in SDH complex genes have been described in patients with the Carney–Stratakis syndrome (CSS), a rare inherited condition that predisposes to GIST and paraganglioma. We report two pediatric patients with multifocal GIST, harboring respectively a novel and a previously reported loss-of-function germline variant, in SDHC and SDHB genes.