Central and peripheral autonomic failure in cold induced sweating syndrome type 1

Cold-induced sweating syndrome type 1 (CISS1) is a rare disorder characterized by profuse sweating in a cold environment, determined by mutations in cytokine receptor–like factor 1 (CRLF1). Its pathogenesis is not fully understood. It has been demonstrated in vitro that CRLF1 may be involved in inducing differentiation from a noradrenergic to a cholinergic transmitter phenotype. During development, catecholaminergic and cholinergic neurotransmission is required for the induction of secretory function, whereas cholinergic transmission becomes crucial for the maintenance of the secretory responsiveness. The abnormal sweat response in CISS1 could be also related to alterations in temperature signals acting on hypothalamus and preoptic areas. We report clinical, molecular, skin biopsy, and temperature monitoring data of an Italian boy with CISS1.