Do not order a periodic fever genetic panel in patients with a classic presentation of PFAPA syndrome without features concerning for other genetic periodic fever syndromes.

Periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA) syndrome is a clinical diagnosis, and currently, no genetic mutations have been identified for this condition. Periodic fever genetic panel in patients with classic features of PFAPA—without any features of another periodic fever syndrome—rarely yields an alternate diagnosis and as such is costly and has no clinical benefit. However, genetic testing may be warranted if patients have atypical features at presentation, don’t respond to treatment as expected, or develop concerning features over time.
For more information:

Berkun Y, Levy R, Hurwitz A, et al. The familial Mediterranean fever gene as a modifier of periodic fever, aphthous stomatitis, pharyngitis, and adenopathy syndrome. Semin Arthritis Rheum. 2011 Apr;40(5):467-72. PMID: 20828792.

Dagan E, Gershoni-Baruch R, Khatib I, Mori A, Brik R. MEFV, TNF1rA, CARD15 and NLRP3 mutation analysis in PFAPA. Rheumatol Int. 2010 Mar;30(5):633-6. PMID: 19579027.

Gattorno M, Caorsi R, Meini A, et al. Differentiating PFAPA syndrome from monogenic periodic fevers. Pediatrics. 2009 Oct;124(4):e721-8. PMID: 19786432.