In the present report we describe a family carrying a very rare heterozygous variant in the SOCS1 gene, with a history of recurrent fever, multiple autoimmune manifestations, and, as the first report in the literature, neurological involvement represented by multiple sclerosis (MS), autoimmune encephalitis and recurrent complex regional pain syndrome, with evidence of altered intraepidermal nerve fiber density on skin biopsy. Here, SOCS1 is linked to multiple sclerosis.