Table 2.

Consensus recommendations on the role of genetics and consanguinity in HLH.

S. No.	Recommendation	Grade of evidence	Level of agreement (%)
6.	The high prevalence of autosomal recessive pathogenic variants in primary HLH (including PRF1, UNC13D, STX11, and STXBP2) supports early genetic evaluation using NGS-based HLH panels, particularly in the setting of parental consanguinity. Where local NGS is unavailable, referral testing should be arranged without delaying management.	Moderate	93% (14/15)
7.	Population-specific enrichment of pathogenic variants in HLH-related genes (such as PRF1, UNC13D, RAB27A, and LYST) supports the development of region-specific genetic panels to enhance screening and early diagnosis of primary HLH.	Low	93% (14/15)
8.	Early genetic testing should be strongly considered in GCC patients with HLH without clear secondary triggers, particularly in infants, young children, or consanguineous families, to guide prognosis, HSCT planning, and family counseling.	Moderate	100% (15/15)
9.	Formal integration of genetic counseling into premarital and prenatal care should be recommended to improve carrier screening, reproductive planning, and prevention of inherited genetic disorders.	Moderate	87% (13/15)

Level of agreement was calculated as the proportion of respondents selecting either “agree” or “somewhat agree.”.

GCC, Gulf Cooperation Council; HLH, hemophagocytic lymphohistiocytosis; HSCT, hematopoietic stem cell transplantation; LYST, lysosomal trafficking regulator; NGS, next-generation sequencing; PRF1, perforin 1; RAB27A, RAB27A member RAS oncogene family; STX11, syntaxin 11; STXBP2, syntaxin-binding protein 2; UNC13D, UNC-13 homolog D.