Patients will undergo clinical evaluations that include history and physical examinations, blood sampling, radiological exams, genetic testing, skin biopsy, and other medically indicated procedures. Genetically related family members of patients may also be evaluated or screened for clinical, in vitro, and genetic correlates of immune abnormalities. Patients and relatives unable or too sick to travel to NIH Clinical Center (CC) may be evaluated through mail-in blood samples. Patients and their relatives will remain enrolled on this study to observe the natural history of the disorder and obtain blood, saliva, skin biopsy, or other specimens at periodic intervals. This study aims to enroll up to a total of 500 patients and their family members.