Expression of CNTFR in the embryonic muscle tissues [6, 19, 20] and CLCF1 and CRLF1 deficiency during development most likely link to the abnormal muscle contractions observed in the patient, the orofacial muscle hypotonia, and the other neuromuscular features that CISS patients have [21, 22]; CNTFR also has been found to play a role in bone formation and metabolism [21, 22] leading to the musculoskeletal deformities patients with CISS have at birth. This evidence concerns the gene CLCF1 and cold-induced sweating syndrome.