Case Report: Familial Cold Autoinflammatory Syndrome With Double Variant in NLRP12 and SETD1A

The inflammasome is a protein complex involved in the activation of inflammatory responses through the production of proinflammatory cytokines and pyroptosis. NLRP12 is a NOD-like receptor that regulates inflammation and inflammasome signaling. Mutations in the NLRP12 gene can lead to familial cold autoinflammatory syndrome type 2 (FCAS2), an autosomal dominant disorder characterized by episodes of fever, urticaria, arthritis, and symptoms triggered by cold exposure. This work presents the case of a pediatric patient with a history of recurrent infections, allergies, and epileptic seizures associated with immunoglobulin administration. Exome sequencing identified two variants: one in the SETD1A gene, associated with neurodevelopmental disorders, and another in NLRP12, previously reported as benign. However, due to the clinical presentation compatible with FCAS2 and signs of immunodeficiency, it is suggested that the NLRP12 variant might have an underestimated pathogenic role. This case highlights the need for further studies to better understand the clinical variability of autoinflammatory diseases and their relationship with genetic variants, as well as the importance of developing targeted treatments.