Definition:

Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disease and characterized by immune dysregulation and microthrombocytopenia. Several nonsense and missense mutations as well as deletions and insertions of the WAS gene have been identified in WAS patients. DiGeorge/velocardiofacial syndrome (DGS) is a congenital immune disorder characterized by lack of embryonic development or underdevelopment of the thymus and surrounding organs. The DGS is a member of a group of disorders that have in common a chromosome deletion involving 22q11.2 (the DiGeorge syndrome chromosome region, or DGCR). Hyper-IgE syndrome (HIES) is characterized by atopic dermatitis associated with extremely high serum IgE levels and susceptibility to infections with extracellular bacteria. Dominant-negative mutations in the signal transducer and activator of transcription 3 (STAT3) gene result in the classical multisystem form of HIES, whereas a null mutation in the tyrosine kinase 2 (TYK2) gene causes an autosomal recessive HIES associated with viral and mycobacterial infections. X-linked lymphoproliferative syndrome (XLP) is a rare primary immunodeficiency, with manifestations ranging from fatal infectious mononucleosis to B cell lymphomas and hypogammaglobulinemia. Mutations in the X-linked inhibitor of apoptosis (XIAP) as well as in a distinct gene, SLAM-associated protein (SAP/DSP1/SH2D1A) have been identified in patients with XLP. Recently, it has been shown that a homozygous mutation in the SH2 domain of the IL-2-inducible T-cell kinase (ITK) gene is associated with fatal Epstein Barr virus associated lymphoproliferation, with a clinical picture similar to that seen in XLP. Immune dysregulation, polyendocrinopathy, enteropathy and X-linked (IPEX) syndrome and autoimmune polyendocrinopathy, candidiasis, ectodermal dysplasia (APECED) are examples of dysregulated immunity resulting in a disturbed tolerance and multiple autoimmune phenomena. IPEX is caused by mutations in the FOXP3 gene, and APECED results from mutations in the autoimmune regulator (AIRE) gene. Cartilage hair hypoplasia (CHH) is due to either the homozygous or compound heterozygous mutations in the nuclear encoded, non-coding RNA gene RMRP.