PRF1 and hemophagocytic syndrome: In this cohort, of the 281 (56%) patients who had a sporadic HLH, 43 had heterozygous mutations in one of the FLH-related genes, such as PRF-1 or UNC13D. The authors propose three forms of HLH: secondary HLH, where no mutation in FLH genes exists and a strong trigger such as a Leishmania infection drives the condition; sporadic HLH, when the patient has a monoallelic mutation in an FLH-related gene where the trigger plays a moderate role; and genetic HLH, where biallelic mutations in FLH-defining genes can cause HLH with no or mild triggers like commonly encountered viral pathogen.