Crisponi syndrome

Crisponi syndrome, also known as cold-induced sweating syndrome type 1 (CISS1), is an extremely rare autosomal recessive disorder caused by mutations in the CRLF1 (cytokine receptor-like factor 1) gene on chromosome 19p13. It was first described in Sardinian families and primarily affects the autonomic nervous system, musculoskeletal system, and thermoregulatory mechanisms. The condition is characterized by neonatal onset of distinctive facial features, muscular contractions of facial muscles resembling trismus (jaw clenching) triggered by tactile stimulation, feeding difficulties, hyperthermia, and episodes of unexplained high fever. Affected infants often display camptodactyly (flexion contractures of the fingers), broad nose, full cheeks, and a characteristic pursed-lip facial appearance. In the neonatal period, Crisponi syndrome carries a high mortality risk, primarily due to hyperthermia and respiratory complications. Infants who survive the critical neonatal period may develop a phenotype that overlaps significantly with cold-induced sweating syndrome (CISS), characterized by profuse sweating of the face and upper body in response to cold temperatures, progressive scoliosis, and feeding difficulties. The trismus and muscular contractions typically improve with age in surviving patients. There is currently no specific or curative treatment for Crisponi syndrome. Management is supportive and symptomatic, focusing on careful thermoregulation, nutritional support (often requiring nasogastric or gastrostomy tube feeding), monitoring and management of respiratory complications, and physical therapy for musculoskeletal manifestations. Antipyretic measures and environmental temperature control are critical in the neonatal period. Genetic counseling is recommended for affected families. The recognition that Crisponi syndrome and cold-induced sweating syndrome represent a clinical continuum caused by CRLF1 mutations has improved understanding and long-term prognostication for affected individuals.

Common questions about Crisponi syndrome