Familial Mediterranean fever in Azerbaijani children: a nationwide cohort study of genotype–phenotype association

Abstract Objectives Familial Mediterranean fever (FMF) is highly prevalent in Mediterranean populations, yet data from Azerbaijan remain scarce despite its location within the traditional FMF belt. This study presents the first nationwide characterization of pediatric FMF in Azerbaijan. Methods A multicenter retrospective cohort study was conducted across pediatric and genetic referral centers in eleven regions of Azerbaijan. Demographic, clinical, and genetic data were analyzed. Genotype–phenotype associations were evaluated with particular emphasis on exon-based variant distribution, exon 10 allelic burden. Results A total of 349 pediatric patients (60.45% boys) were enrolled. The median age at symptom onset and diagnosis was 4 (0-18) and 7 (0-23) years, respectively. The most prevalent MEFV variants were M694V (47.3%), V726A (20.1%), and R202Q (19.8%). Zygosity distribution: 18.3% homozygous, 40% heterozygous, and 41.5% compound heterozygous. Genotype–phenotype analyses included 329 patients after excluding isolated R202Q heterozygotes. Fever (79.3%) and abdominal pain (66.6%) were the most frequent manifestations. Compound heterozygous exon 10 genotypes were associated with earlier symptom onset in univariate analyses. In multivariable hierarchical logistic regression analyses, the presence of at least one M694V allele independently increased the likelihood of early-onset disease (OR 2.10, 95% CI 1.29–3.43, p = 0.003), while the zygosity-based model supported an association between biallelic exon 10 involvement and early disease onset. Conclusion This first nationwide pediatric FMF study from Azerbaijan reveals substantial regional genetic heterogeneity, with compound heterozygosity associated with earlier disease onset. These findings advance FMF epidemiology in the Caucasus and support improved genetic counseling and surveillance for high-risk genotypes.