Evaluation of pediatric FMF patients with biallelic pathogenic exon 10 variants: focus on chest pain

Chest pain occurs in approximately one-quarter of patients with FMF, the most common monogenic autoinflammatory disease characterized by recurrent attacks of fever and serositis. This study evaluated a large, genetically homogeneous pediatric FMF cohort carrying biallelic pathogenic exon 10 MEFV variants to describe their demographic, clinical, and genetic characteristics, and to compare patients with and without chest pain to better define this manifestation within the FMF spectrum. This cross-sectional single-center study included 918 pediatric FMF patients with biallelic pathogenic MEFV exon 10 variants followed between June 2016 and February 2025. Demographic, clinical, and genetic data were collected retrospectively, and comparative analyses were performed between patients with and without chest pain. The cohort included 456 females (49.7%), with a median age of onset of 4.0 years and diagnosis age of 6.0 years. The most common genotype was M694V/M694V (48.9%), and 12.4% had colchicine resistance. Chest pain occurred in 218 (23.7%) patients, all pleuritic in origin, with no pericarditis. Those with chest pain had higher annual attack frequency, more abdominal pain (95% vs. 87%, p = 0.001) and greater colchicine resistance (21.1% vs. 9.7%, p = 0.001). The M694V/M694V genotype was significantly more frequent in those with chest pain (p = 0.017). Among patients presenting with chest pain, radiologically confirmed pleural effusion was detected in 5% during at least one of their evaluated attacks, predominantly among those with colchicine resistance.

In this large genetically homogeneous pediatric FMF cohort, chest pain was a frequent pleuritic manifestation. Patients with chest pain showed higher attack frequency and greater colchicine resistance, particularly among M694V homozygotes. Although rare, detected pleural effusion in patients with chest pain was associated with a significantly higher rate of colchicine resistance.

• Chest pain is a recognized but variably reported manifestation of FMF, usually pleuritic in origin. • The M694V homozygous genotype is associated with more severe inflammatory phenotypes.

• In a large genetically homogeneous pediatric cohort, chest pain occurred in nearly one-quarter of patients and was linked to higher attack frequency. • Chest pain was strongly associated with colchicine resistance and more frequent in M694V/M694V patients. Additionally, a high frequency of colchicine resistance was observed in patients with detected pleural effusion.