PReS-FINAL-2325: Different phenotypes associated with Q703K variant of the NLRP3 gene

Results We found the NLRP3 variant Q703K in 13 patients. Ten were PFAPA patients among 97 from our cohort; one had a CAPS phenotype and two an undefined autoinflammatory disease (UAID): 9 boys and 4 girls with a median age of 18 months at disease onset. Family history was positive in 6 PFAPA and one UAID patients. For PFAPA, the median duration of fever was 4 days; the median interval was 4 weeks. Pharyngitis and cervical adenitis was always present in 6 patients. Aphtosis was found only in 1 patient in every episode. 5 patients expressed abdominal pain that accompanied most fever episodes. 1 patient showed sometimes arthralgia, 2 patients had headaches in most episodes and one patient had once a cutaneous rash. 5 out of 7 patients treated by corticosteroids responded promptly. In the other two patients two doses were often necessary. 3 patients underwent tonsillectomy: one with no effect, in 2 the fever episodes resolved but one patient had persistent episodes of aphtosis. In 4 patients genomic sequencing of the parents was done; one parent positive for Q703K had a history of recurrent febrile episodes, but the 3 other parents did not present a history of recurrent fever episodes nor recurrent pharyngitis nor tonsillectomy. The patient with CAPS phenotype presented with urticarial rash, partial deafness, arthralgias and elevated inflammatory parameters, and responded well to IL-1 blocking agents. One patient with UAID presented recurrent fever episodes with neurological symptoms (hypotonia, bulging fontanelle, loss of contact) and high inflammatory markers, and the second with fever flares and angioedema. In one UAID and two PFAPA patients another heterozygous variant in the MEFV gene was found.