title: Clinical features and genetic background of the periodic Fever syndrome with aphthous stomatitis, pharyngitis, and adenitis: a single center longitudinal study of 81 patients.
abstract: PFAPA syndrome is the most common autoinflammatory disorder in childhood with unknown etiology. The aim of our study was clinical evaluation of PFAPA patients from a single tertiary care center and to determine whether variations of AIM2, MEFV, NLRP3, and MVK genes are involved in PFAPA pathogenesis. Clinical and laboratory data of consecutive patients with PFAPA syndrome followed up at the University Children's Hospital, Ljubljana, were collected from 2008 to 2014. All four genes were PCR amplified and directly sequenced. Eighty-one patients fulfilled criteria for PFAPA syndrome, 50 (63%) boys and 31 (37%) girls, with mean age at disease onset of 2.1 ± 1.5 years. Adenitis, pharyngitis, and aphthae were present in 94%, 98%, and 56%, respectively. Family history of recurrent fevers in childhood was positive in 78%. Nineteen variants were found in 17/62 (27%) patients, 4 different variants in NLRP3 gene in 13 patients, and 6 different variants in MEFV gene in 5 patients, and 2 patients had 2 different variants. No variants of clinical significance were found in MVK and AIM2 genes. Our data suggest that PFAPA could be the result of multiple low-penetrant variants in different genes in combination with epigenetic and environmental factors leading to uniform clinical picture.
authors.affiliation: Department of Allergology, Rheumatology and Clinical Immunology, University Children's Hospital, University Medical Center, Bohoričeva 20, 1000 Ljubljana, Slovenia.
authors.forename: Daša
authors.initials: D
authors.lastname: Perko
authors.affiliation: Unit for Special Laboratory Diagnostics, University Children's Hospital, University Medical Center, Bohoričeva 20, 1000 Ljubljana, Slovenia.
authors.forename: Maruša
authors.initials: M
authors.lastname: Debeljak
authors.affiliation: Department of Allergology, Rheumatology and Clinical Immunology, University Children's Hospital, University Medical Center, Bohoričeva 20, 1000 Ljubljana, Slovenia ; Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia.
authors.forename: Nataša
authors.initials: N
authors.lastname: Toplak
authors.affiliation: Department of Allergology, Rheumatology and Clinical Immunology, University Children's Hospital, University Medical Center, Bohoričeva 20, 1000 Ljubljana, Slovenia ; Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia.
authors.forename: Tadej
authors.initials: T
authors.lastname: Avčin
mesh_terms: D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003598:Cytoskeletal Proteins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005334:Fever / Q000235:genetics*; D000068617:Genetic Background; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D008199:Lymphadenitis / Q000235:genetics*; D008297:Male; D009154:Mutation; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010612:Pharyngitis / Q000235:genetics*; D000071198:Pyrin; D013281:Stomatitis, Aphthous / Q000235:genetics*; D013577:Syndrome
chemical_list: C410167:AIM2 protein, human; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; C000604192:MEFV protein, human; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D000071198:Pyrin
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