Whole exome sequencing (WES) identified a heterozygous variant in STXBP2 and another in LYST. Intriguingly, the patient’s mother also carried these two variants and had severely impaired NK cell function, but had never developed HLH, again suggesting that additional environmental and genetic factors may have cooperated with underlying degranulation pathway dysfunction to trigger HLH in this patient. This evidence concerns the gene STXBP2 and hemophagocytic syndrome.