Additionally, bi-allelic mutations in DSG1 gene have also been recently reported in the severe SAM syndrome, characterized by sinusitis, palmoplantar keratoderma, erythroderma, multiple allergies and metabolic defects, with heterozygous mutation carriers only presenting hyperkeratotic palmoplantar lesions [15]. This evidence concerns the gene DSG1 and epidermolytic palmoplantar keratoderma, 1.