CRLF1 and Down syndrome: Crisponi/cold-induced sweating syndrome 1 (CISS1/CISS; MIM#272430) is a rare autosomal recessive disorder caused by biallelic variants in the cytokine receptor-like factor 1 gene (CRFL1, MIM*604237) [1], located on chromosome 19p13 and encoding cytokine receptor-like factor-1 (CRLF1), a member of the ciliary neurotrophic factor receptor pathway [2].