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Review
. 2019 May 14;17(1):22.
doi: 10.1186/s12969-019-0324-7.

Periodic fever syndromes: beyond the single gene paradigm

Clara Westwell-Roper  1   2 , Iwona Niemietz  3   2 , Lori B Tucker  4   5 , Kelly L Brown  1   2
Affiliations
Review

Periodic fever syndromes: beyond the single gene paradigm

Clara Westwell-Roper et al. Pediatr Rheumatol Online J. .

Abstract

Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease in Canada and is characterized by a clinical syndrome of episodic inflammatory symptoms. Traditionally, the disease is defined by autosomal recessive inheritance of MEFV gene variants, yet FMF also not uncommonly manifests in individuals with only one identified disease-associated allele. Increasing availability and affordability of gene sequencing has led to the identification of multiple MEFV variants; however, they are often of unknown clinical significance. Variants in other genes affecting overlapping or distinct inflammatory signaling pathways - together with gene-environment interactions including epigenetic modulation - likely underlie the significant genetic and phenotypic heterogeneity seen among patients with this disease. We review recent evidence of the expanding spectrum of FMF genotype and phenotype and suggest that current drug funding schemes restricting biologic agents to patients with homozygous mutations have not kept pace with our biological understanding of the disease.

Keywords: Biological therapy; Familial Mediterranean fever; Genetic association studies; Hereditary autoinflammatory diseases; Interleukin-1; Pyrin.

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Conflict of interest statement

Ethics approval and consent to participate

The CAN Fever Autoinflammatory Disease Registry at BC Children’s Hospital has ethics approval from the UBC Children and Women’s Research Ethics Board, and all data described in this manuscript was collected from consented patients and families.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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