Phenotypic Presentation of Four Patients with Novel Mutations for Periodic Fever Syndromes
Sunday, March 4, 2018
South Hall A2 (Convention Center)
Rachel Eisenberg, MD, Shikha Gupta, MD, Arye Rubinstein, MD FAAAAI
RATIONALE: There are well described mutations and inheritance patterns of periodic fever syndromes. Varying phenotypic presentations with complicated genetic patterns are increasingly being reported. We describe four patients with unique periodic fever mutations.

METHODS: Case Series

RESULTS: We describe four patients of varying descent who presented with recurrent fevers and multiple associated symptoms including lymphadenopathy, aphthous ulcers, arthralgia’s and abdominal pain. All four patients demonstrated abnormalities in interleukin 1 beta or interleukin 6, as described commonly in periodic fever syndromes. They had varying responses to acetaminophen, NSAID and steroids. Genetic testing through GeneDx for complete periodic fever panel revealed mutations either previously not described or of unknown pathogenic significance. Two patients were noted to have heterozygous mutations on the MEFV gene associated with FMF, one being V726A which is usually pathogenic when inherited in homozygous pattern and the other R329H of unknown pathogenic significance. The third patient had a heterozygous R121Q mutation on the TNFRSF1A gene associated with TRAPS and thought to have low penetrance. The fourth patient had a heterozygous D938N mutation of unknown clinical significance on NLRP3 associated with Cryopyrin Associated Periodic Syndromes (CAPS).

CONCLUSIONS: We describe four patients with recurrent fevers and typical features of periodic fevers who demonstrated uncommon or novel mutations on known periodic fever genes. Our cases highlight the complexity of genetic analysis and emergence of varying phenotypes. It remains unclear whether these patients are at risk for complications such as amyloidosis. If clinically indicated, cytokine targeted therapies should be considered in these patients despite unusual genetic testing.