Our cases and literature review further expand existing knowledge on the phenotype and <i>TRNT1</i> variations of SIFD and suggest that the early genomic diagnosis of <i>TRNT1</i> is valuable to promptly assess bone marrow transplantation and tumor necrosis factor inhibitor treatments, which might be effective for the immunodeficiency and inflammation caused by SIFD. This evidence concerns the gene TNF and immunodeficiency disease.