Severe Neonatal Infection in Crisponi Syndrome: A Diagnostic Challenge in a Preterm Infant

Crisponi syndrome, also referred to as cold-induced sweating syndrome type 1, is an uncommon autosomal recessive disorder caused by mutations in the cytokine receptor-like factor 1 (CRLF1) gene. The disorder typically presents with distinctive craniofacial abnormalities, feeding impairment, stimulus-induced muscle spasms, and varying degrees of autonomic dysfunction. Neonates affected by this condition are particularly vulnerable to respiratory complications and infections, especially in the setting of prematurity. We report a case of a preterm male neonate born at 34 weeks of gestation to consanguineous parents, presenting with characteristic dysmorphic features and early-onset stimulus-induced spastic episodes. Initially suspected to have hypoxic-ischemic encephalopathy, the patient later developed severe respiratory distress and sepsis secondary to bilateral pneumonia. Laboratory findings showed progressive inflammatory markers, hematological abnormalities, and a positive blood culture for Enterobacter species. Retrospective assessment using the neonatal Sequential Organ Failure Assessment score yielded a score of 11, indicating severe organ dysfunction and high mortality risk. Whole exome sequencing confirmed a homozygous likely pathogenic variant in the CRLF1 gene, consistent with Crisponi syndrome. Despite intensive care management, the patient succumbed to multiorgan failure. This case highlights the diagnostic challenges in distinguishing neurological manifestations of Crisponi syndrome from hypoxic brain injury and underscores the high risk of severe infection in affected preterm neonates. Early genetic diagnosis and multidisciplinary management are critical for improving outcomes.