The Phenotype-Genotype Correlations of FMF Patients: A Single Center Study

Purpose: Familial Mediterranean Fever (FMF) is an autosomal recessive, auto-inflammatory disease that is characterized by recurrent fever and polyserositis episodes like peritonitis, arthritis, and pleuritis. The disease occurs most commonly in populations of Jewish, Turkish, Armenian, and Arabian origin. We aimed to show the genotype-phenotype relationship in FMF patients in our centre. Materials and Methods: We conducted a retrospective analysis of the medical registries of 200 FMF pediatric patients from Sisli Hamidiye Etfal Education and Research Hospital, Department of Pediatrics, Pediatric Nephrology Policlinic between 2011 and 2017. The diagnosis was based on the Tel-Hashomer clinical diagnostic criteria. We used the severity score recommended by Pras in 1998. Clinical data and baseline investigations were collected. Mutation analysis was performed by the amplification-refractory mutation system (ARMS)-PCR method. Findings: Females represented 54% and ages ranged from 40-210 months. The most frequent symptoms were abdominal pain, fever, and arthralgia.Among the 200 patients, 41 (20,5%) were homozygous, 63 (31,5%) were compound heterozygous, and 96 (48%) were heterozygous for MEFV mutations. The first 3 most common mutations were heterozygotus R202Q, M694V/R202Q and heterozygotus E148Q respectively., which was statistically significant. M694V mutation was positive in at least one allele in 72 patients studied. The symptom of fever and arthralgia were found to be significantly higher in patients with M694V mutation. Also, the number of episodes in one year before treatment, PRAS score and the values of fibrinogen during episodes were higher in M694V patients as a result, the age at diagnosis was found to be earlier in patients with homozygotus M694V mutation. The ratio of female gender and myalgia was significantly higher in patinets with the mutation of R202Q homozygotus. The number of episodes in one year before treatment was lower in R202Q patients when compared to the M694V carriers, therefore the initiation age to colchicine was later in the R202Q group which was statistically significant. İmplications to Theory, Practice and Policy: Our results support the notion that the genotype influences the phenotype as regards clinical manifestations, disease severity, and colchicine response.