Characteristics of Siblings with Familial Mediterranean Fever: A Single-Center Experience

Area of Science:

• Genetics and Immunology
• Autoinflammatory Diseases
• Pediatric Rheumatology

Background:

• Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disorder.
• Limited data exists on the clinical characteristics of FMF in sibling cohorts.
• Understanding familial FMF presentation is crucial for accurate diagnosis and management.

Purpose of the Study:

• To investigate the clinical features and genetic profiles of siblings diagnosed with FMF.
• To compare disease presentation, severity, and treatment response among FMF siblings.
• To identify factors influencing phenotypic variability in familial FMF.

Main Methods:

• Retrospective, cross-sectional study of 143 FMF siblings from 65 families.
• Patients categorized into two groups based on diagnosis order: first diagnosed child (Group I) and later diagnosed sibling (Group II).
• Analysis included genetic mutations, attack symptoms, Pras disease severity score, and colchicine treatment response.

Main Results:

• 72% of siblings shared identical FMF genetic mutations.
• Despite shared mutations, 59% had different attack symptoms, 56% differed in disease severity, and 45% varied in colchicine response.
• Fever and abdominal pain were more frequent in Group I; Group I also had an earlier age of disease onset.

Conclusions:

• Significant clinical heterogeneity exists among FMF siblings, even with the same genetic mutation.
• Phenotypic variability underscores the importance of comprehensive FMF symptom awareness for families.
• Genetic factors alone do not fully predict FMF clinical presentation or treatment outcomes in siblings.