Disorders associated with prominent defects in ectodermal development include those arising from IKBKG and NFKBIA variants, manifesting as ED with loss of skin appendages, and popliteal-pterygium spectrum (Bartsocas-Papas syndrome), from defects in CHUK and RIPK4. By contrast, defects of regulatory proteins (A20, OTULIN) result in predominantly inflammatory manifestations of mucocutaneous ulceration and neutrophil accumulation in the skin, features that make these syndromes an important differential diagnosis for Behcet's disease. The gene discussed is OTULIN; the disease is Bartsocas-Papas syndrome 1.