Phenotype–genotype relationship and evaluation of disease severity in pediatric patients diagnosed with Familial Mediterranean Fever
Abstract
Aims: Familial Mediterranean Fever (FMF) is a monogenic autoinflammatory disease caused by mutations in the MEFV gene and characterized by recurrent inflammatory attacks. The present study aimed to evaluate the relationship between clinical findings, MEFV mutation distribution, and disease severity in pediatric patients diagnosed with FMF.
Method: This retrospective study included 115 FMF patients younger than 18 years who followed at least one year at Ankara Training and Research Hospital between January 2005 and January 2010. Demographic characteristics, clinical manifestations, attack frequency, laboratory findings, colchicine doses, MEFV gene mutations were obtained from medical records. FMF was diagnosed according to the Yalçınkaya–Özen diagnostic criteria. Disease severity was classified as mild, moderate, or severe using a scoring system based on clinical and laboratory parameters. Statistical analyses were performed using appropriate methods.
Results: Among the patients, 55.7% were female, and the mean age was 11 ± 4 years. The mean age at symptom onset was 5 ± 3.8 years, whereas the mean age at diagnosis was 8 ± 3.8 years. The most common clinical manifestations were abdominal pain (92.2%), fever (88.7%), and arthralgia (56.5%). Homozygous or compound heterozygous mutations were identified in 79.1% of patients, with M694V/M694V being the most frequent genotype (38.2%). According to disease severity scores, 34.8% of patients had mild disease, 61.0% had moderate disease, and 3.5% had severe disease. Differences among mutation groups were observed regarding abdominal pain and vasculitis, whereas no significant differences were found for other clinical manifestations or attack frequency.
Conclusion: The relationship between MEFV mutations, clinical phenotype, and disease severity in pediatric FMF appears to be complex and multifactorial. Although the homozygous M694V mutation has been associated with severe disease in some patients, the phenotype-genotype relationship is not always linear. These findings suggest that factors beyond genotype may influence disease expression and severity in pediatric FMF.
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References
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Details
Primary Language
English
Subjects
Clinical Sciences (Other)
Journal Section
Research Article
Publication Date
September 27, 2026
Submission Date
January 23, 2026
Acceptance Date
July 17, 2026
Published in Issue
Year 2026 Volume: 6 Number: 3