Clinical spectrum of pediatric patients carrying heterozygous MEFV gene variants.

The MEditerranean FeVer (MEFV) gene is a critical regulator of the innate immune response. The prototypical disease related to the MEFV gene is familial Mediterranean fever (FMF). Heterozygous MEFV gene variants have increasingly been reported in association with a wide range of inflammatory disorders besides FMF. The aim of this study was to evaluate the diagnostic spectrum and clinical and demographic findings of patients carrying heterozygous MEFV variants. This retrospective study included pediatric patients carrying heterozygous MEFV variants who were followed up at our center between January 2012 and January 2025. Diagnosis, demographics, and clinical manifestations were reviewed. A total of 270 patients with a median age of 7 years were identified. The diagnoses of the study population included FMF (67%), IgA vasculitis (7%), PFAPA syndrome (6%), inflammatory bowel disease (3%), juvenile idiopathic arthritis (3%), chronic nonbacterial osteomyelitis (2%), Behçet's disease (1%), and other vasculitides (1%). Fourteen percent of the patients were asymptomatic carriers. During follow-up, 22 of the 74 patients (30%) initially diagnosed with other inflammatory conditions later developed clinical features consistent with FMF. Colchicine therapy was initiated not only for typical attacks of FMF but also for selected indications in other inflammatory diseases.

conclusionHeterozygous MEFV variants have been reported to be associated with various inflammatory diseases besides FMF. Long-term follow-up is essential, as some patients may later develop FMF. MEFV gene testing should be considered in other inflammatory diseases with severe or atypical manifestations, particularly in populations where FMF is highly prevalent. WHAT IS KNOWN: •  Heterozygous MEFV variants have been associated with FMF and several inflammatory diseases. WHAT IS NEW: • This large pediatric cohort demonstrates that heterozygous MEFV variants may be encountered across a broad spectrum of inflammatory diseases, and some patients initially diagnosed with other conditions may subsequently develop FMF during follow-up.