NIH Researchers Uncover Genes Linked to Common Recurrent Fever in Children

Researchers at NHGRI have discovered clues to the possible cause of recurring, non-contagious fevers and sores that affect only children. Several genes have been implicated with the syndrome, known as PFAPA syndrome (Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis), which could lead to new treatments. 

Results were published June 8 in the journal PNAS.

The findings were made possible by the realization of commonalities with other chronic inflammatory conditions that also involved sores on the body, including the common canker sore. The study illustrates how long-standing health mysteries may now be solved when researchers discover new biological connections with the help of increasing amounts of genomic data.

In 1987, researchers first described a syndrome seen in 12 children, which was marked by recurrent fever, painful canker sores, sore throat and inflamed lymph nodes. The condition starts early in life, between the ages of 1 and 5. The first sign is fever, accompanied by sore throat with redness and other symptoms.

“PFAPA syndrome is the most periodic of periodic fevers, with many children having an episode every month lasting 3 to 5 days,” said Dr. Kalpana Manthiram, clinical fellow at NHGRI and lead author of the study. “That is an immense burden on families since these kids cannot go to school and may be bedridden for days during flares.”

While PFAPA syndrome has become the most common recurring fever syndrome in children from Western countries, diagnosis and treatment methods have remained largely primitive and insufficient. The episodes usually spontaneously stop in pre-adolescence.

Because of the nature of the disease, researchers have long thought that answers may lie in genomics. After ruling out the possibility that the syndrome is caused by mutations in a single gene, they considered the possibility that multiple genes are involved.