Clinical and MEFV variant characteristics of pediatric patients with an FMF-compatible phenotype and PFAPA-compatible features in a Palestinian referral cohort: a retrospective study

Familial Mediterranean fever (FMF) and periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome may share clinical manifestations, complicating phenotypic classification in children from populations in which MEFV variants are frequent. This study characterized the clinical and genetic features of a pediatric Palestinian referral cohort with an FMF-compatible phenotype and described the subgroup that also fulfilled PFAPA clinical classification criteria. This retrospective two-center cohort included 169 patients aged ≤ 18 years who were retrospectively classified with an FMF-compatible phenotype using available clinical and genetic information and the Eurofever/PRINTO classification framework. Patients were subsequently assessed for PFAPA-compatible features using the corresponding clinical classification criteria. Genetic analyses were restricted to the 143 patients with available MEFV testing. Of the 169 patients with an FMF-compatible phenotype, 32 (18.9%) additionally fulfilled PFAPA clinical classification criteria. MEFV genetic testing was available in 124/137 (90.5%) patients with an FMF-only phenotype and 19/32 (59.4%) patients with PFAPA-compatible features. Among the 143 genetically tested patients, M694V was the most frequently recorded variant, occurring in 84 (58.7%). Of the 19 genetically tested patients with PFAPA-compatible features, 10 were recorded as heterozygous; E148Q was the most frequent heterozygous variant pattern. Clinical manifestations incorporated into the PFAPA classification algorithm were interpreted descriptively rather than as independent between-group associations. A subgroup of children classified with an FMF-compatible phenotype also fulfilled PFAPA clinical classification criteria. The findings demonstrate clinical overlap but do not establish coexistence of two independent diseases or a causal genotype–phenotype relationship. Unequal availability of genetic testing and the limitations of retrospective phenotypic classification warrant cautious interpretation.