Atypical Neurological Presentation of Familial Mediterranean Fever Mimicking Refractory Childhood Epilepsy

Familial Mediterranean fever (FMF) is a monogenic autoinflammatory disorder classically characterized by recurrent episodes of fever and polyserositis. Although central nervous system involvement is rare, FMF can atypically present with severe neurological manifestations, including seizure disorders. The authors report the highly unusual case of a 27-year-old male who was misdiagnosed with West syndrome at 8 months of age and was subsequently treated with multiple antiepileptic drugs (AEDs) for over 2 decades. The patient was initially referred for the evaluation of chronically elevated C-reactive protein (CRP) and serum amyloid A (SAA) levels of unknown etiology. A detailed medical history revealed recurrent episodes of paradoxical abdominal pain. Genetic analysis identified heterozygous R202Q and M680I mutations in the MEFV gene, establishing the diagnosis of FMF. Strikingly, the initiation of targeted autoinflammatory therapy with colchicine not only normalized his systemic inflammatory markers but also resulted in complete seizure freedom. This profound clinical response enabled the successful withdrawal of his long-term AED polytherapy. This case highlights that refractory, childhood-onset epilepsy can occasionally serve as an atypical neurological mask for FMF. Clinicians must consider autoinflammatory etiologies in patients with treatment-resistant seizures and unexplained systemic inflammation, as targeted therapy can safely reverse years of unnecessary antiepileptic treatment. Cite this article as: Berkkan M, Er Gülbezer, E. Atypical neurological presentation of familial Mediterranean fever mimicking refractory childhood epilepsy. Eur J Rheumatol. 2026, 13(2), 0027, doi:10.5152/eurjrheum.2026.26027.