Zhang and colleagues demonstrated that patients with ISG15-deficient displayed clinical signs of enhanced IFN-α/β immunity as seen in AGS and spondyloenchondrodysplasia (SPENCD) such as cerebral calcifications (nearly 100% of patients with ISG15) and sporadic reports of seizures. The gene discussed is ISG15; the disease is Spondyloenchondrodysplasia with immune dysregulation.