Cold-induced sweating syndrome

Cold-induced sweating syndrome (CISS) is an extremely rare genetic disorder characterized by profuse sweating triggered by cold temperatures, rather than by heat or exercise as would normally occur. This paradoxical sweating response is the hallmark feature of the condition. There are two recognized subtypes: Cold-induced sweating syndrome type 1 (CISS1, also known as Crisponi syndrome in its severe neonatal form) caused by mutations in the CRLF1 gene, and Cold-induced sweating syndrome type 2 (CISS2) caused by mutations in the CLCF1 gene. Both genes encode components of a cytokine signaling complex involved in neuronal development and autonomic nervous system regulation. The condition affects multiple body systems. Key clinical features include profuse sweating induced by cold ambient temperatures, facial dysmorphism (including a round face, depressed nasal bridge, and anteverted nares), high-arched palate, feeding difficulties in infancy, scoliosis or kyphoscoliosis, and skeletal abnormalities. Affected individuals may also exhibit muscular contractions resembling trismus (jaw clenching), episodes of unexplained high fever in infancy, and skin manifestations such as a maculopapular rash. The severe neonatal presentation, historically termed Crisponi syndrome, can include life-threatening episodes of hyperthermia and respiratory distress. Survivors of the neonatal period typically develop the cold-induced sweating phenotype in later childhood. There is currently no cure or specific targeted therapy for cold-induced sweating syndrome. Management is supportive and symptomatic, focusing on avoidance of cold exposure to minimize sweating episodes, monitoring and treatment of scoliosis, management of feeding difficulties in infancy, and careful temperature regulation. Genetic counseling is recommended for affected families. Long-term follow-up with a multidisciplinary team including neurologists, orthopedic specialists, and geneticists is advisable to address the various manifestations of the condition.

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