A comparative analysis of 319 patients with DSBR disorders reported in the literature, including 46 with LIG4 deficiency, 216 with NBS, and 57 with autosomal recessive NHEJ1 variants (seven from this study), revealed that malignancy poses a significant mortality risk for NBS patients. This evidence concerns the gene LIG4 and hyperinsulinemic hypoglycemia, familial, 4.