Genotypic and phenotypic characteristics of pediatric patients with familial Mediterranean fever (a periodic disease) in one of the Russia regions

Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease (AID) caused by mutations in the MEFV gene. The purpose of this research was to investigate clinical variability and potential genotypic and phenotypic correlations in children with clinically verified FMF and MEFV gene mutations in the City of Moscow, Russia. Materials and methods used: among 188 pediatric patients with suspected monogenic AIDs, MEFV gene mutations were identified in 9 through sequencing. In order to confirm the FMF diagnosis, patients were evaluated according to the modified Tel-Hashomer criteria and the Eurofever/PRINTO classification criteria. Results: clinical picture of FMF was characterized by the presence of periodic attacks of the disease lasting from 1 to 7 days accompanied by fever and increased acute phase reactants (observed in all patients), abdominal pain (in 8 children), peritonitis requiring diagnostic laparotomy (in a single child), chest pain (in 2 patients), pleurisy (in a single child), arthritis (in 7 children) and erysipeloid-like rash (in a single child). The pathogenic mutation M694V was identified in the MEFV gene in 8 out of 9 patients, this mutation was homozygous in 5 patients and heterozygous in 1, M680I mutation was detected on another allele in 2 children (compound heterozygous), and a mutation of unknown significance K695R was detected in a single child. No obvious clinical differences were found between homozygotes and heterozygotes as well as compound heterozygotes. Clinical response was achieved in 5 patients with colchicine monotherapy while canakinumab was prescribed to 4 patients due to ongoing attacks. Conclusion: the diagnosis involving the identification of MEFV gene mutations may allow the assessment of genotype-phenotype correlations in patients with FMF.