Hereditary Recurrent Fevers HRF

Who gets HRFs?

It most often occurs in individuals of Mediterranean and Middle Eastern descent with the first episodes typically begins in childhood.

What causes HRF?

Is usually caused by autosomal recessive genetic variations in specific genes where patients inherit from both parents. The parents are called carriers.

The causative genes for HRFs encode proteins involved in the regulation of innate immunity, mainly by affecting proinflammatory cytokines and apoptosis pathways. When there is a genetic defect, inflammation gets out of control, and patients experience episodes of fever and pain.

How is HRF diagnosed?

A DNA test to look for gene mutations will be done in cases where HRF is suspected.

How is HRF treated?

Patients based on the type of monogenic syndrome will be given appropriate treatment to minimize the autoinflammatory response.

Life-long treatment for inflammation is important as it can prevent the complication of organ failure from amyloidosis e.g kidney failure.

Types of Hereditary recurrent fevers (HRFs)

While familial Mediterranean fever (FMF) is relatively the most common in Mediterranean and Middle Eastern population there are other types of HRFs that give similar clinical symptoms. The other three more common are mevalonate-kinase deficiency (MKD), cryopyrin-associated periodic syndrom (CAPS) and tumour necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS).

  • FMF       MEFV gene
  • MVK       MKD gene                         
  • TRAPS    TNFRSF1A gene                
  • CAPS      NLRP3 gene


Genetic Testing for HRFs

HRF presents a wide clinical spectrum with a number of genes involved that have a pivotal role in the regulation of the inflammatory response. The major genes of interest are:

  • MEFV gene, that usually involve genetic screening of the covering 12 known mutations, E148Q, P369S, F479L, M680I (G >C, G >A), I692 del, M694V, M694I, K695R, V726A, A744S, R761H. Exons 2, 3, 5 and 10.
  • MKD gene, screening Exons 8, 9 and 10.
  • TNFRSF1A gene, screening Exons 2, 3 and 4.
  • NLRP3 gene, screening Exon 3.