Limited association of MEFV gene variants with disease severity and clinical phenotypes in children with MIS-C

Abstract Background Multisystem inflammatory syndrome in children (MIS-C) is a post-infectious hyperinflammatory condition that develops after SARS-CoV-2 infection and may involve multiple organ systems, including the cardiovascular, hematologic, neurologic, and gastrointestinal systems. Because MIS-C is characterized by immune dysregulation, genetic factors affecting inflammasome pathways may contribute to disease susceptibility or phenotypic variation. Objective To evaluate the frequency of MEFV gene variants in children with MIS-C and to assess their association with disease severity, laboratory findings, and different clinical manifestations. Methods This study included 98 children diagnosed with MIS-C. All patients were evaluated for MEFV gene variants. Variant frequencies were determined, and associations between MEFV mutation status and disease severity, laboratory parameters, and clinical manifestations were analyzed using the Chi-square test. Results Most patients had no detectable MEFV mutation (81/98, 82.7%), while 17.3% carried at least one variant. The most frequent variant was heterozygous E148Q (7.1%), followed by heterozygous V726A (2.0%), homozygous M694I (2.0%), heterozygous compound E148Q & P369S (3.1%), heterozygous compound M680I & V726A (2.0%), and heterozygous M680I (1.0%). No statistically significant association was found between MEFV variants and MIS-C severity ( p = 0.86). No significant associations were detected between MEFV variants and MISC clinical manifestations. Conclusion Most children with MIS-C in this cohort had no detectable MEFV mutation, and the identified variants were not associated with disease severity or major organ manifestations. These findings do not support a major role for common MEFV variants in determining MIS-C severity, although larger multicenter studies are needed to clarify their potential contribution.