Autoinflammation with infantile enterocolitis induced by a heterozygous variant (c.1357C > T) in the NLRC4 gene: a...

Necrotizing enterocolitis (NEC) is s a life-threatening inflammatory intestinal disorder primarily affecting preterm infants, though rare in full-term neonates. NLR-family CARD domain-containing protein 4 (NLRC4), a cytosolic inflammasome component driving IL-1β-mediated inflammation, is linked to autoinflammatory syndromes via germline gain-of-function mutations, though its role in term infant NEC remains underexplored.

A full-term male infant developed NEC shortly after birth, requiring emergency surgical interventions including ileostomy and intestinal resection. Intraoperative findings revealed multifocal necrosis in the small intestine (80 cm total length) and colon. Genetic testing identified a heterozygous NLRC4 variant (c.1357C > T, p. Arg 453*), inherited from an asymptomatic father. Sanger sequencing confirmed the mutation's de novo origin. Pathological analysis demonstrated transmural inflammation without evidence of Hirschsprung disease.

This report identifies a novel truncating variant in the NLRC4 gene associated with severe autoinflammatory enterocolitis presenting as NEC in a term neonate. Early NLRC4 screening may guide targeted therapies and improve outcomes in severe intestinal inflammation.