Table 2.
Classification of SCID variants based on normal T-cell development
| Inheritance | Phenotype MIM number | Gene/locus MIM number | Specific manifestations | |
|---|---|---|---|---|
| DNA ligase IV deficiency | AR | 606593 | 601837 | Microcephaly, developmental delay, facial dysmorphism, radiation sensitivity. May present with Omenn syndrome or with a delayed clinical onset |
| Cernunnos deficiency | AR | 611291 | 611290 | Microcephaly, developmental delay, in utero growth retardation, radiation sensitivity |
| CD3γ deficiency | AR | 186740 | May present with a benign course | |
| MHC class I deficiency | AR | 604571 | 170260, 170261, 601962 | Necrotizing granulomatous skin lesions |
| CD8 deficiency | AR | 608957 | 186910 | |
| MHC class II deficiency | AR | 209920 | 600005, 601863, 601861, 603200 | |
| Interleukin-2 receptor alpha chain (CD25) deficiency | AR | 606367 | 147730 | Lymphocytic infiltration of tissues (lung, liver, gut, and bone), autoimmunity (may resemble IPEX syndrome) |
| p56lck deficiency | AR | 153390 | ||
| ZAP-70 deficiency | AR | 176947 | ||
| Ca++ channel deficiency | AR | 612782 612783 |
610277 605921 |
Anhydrotic ectodermic dysplasia, nonprogressive myopathy, abnormalities in dental enamel. Unique features of STIM1 deficiency: autoimmunity and partial iris hypoplasia |
| Signal transducer and activator of transcription 5b (STAT5b) deficiency | AR | 245590 | 604260 | Growth-hormone insensitive dwarfism, dysmorphic features, eczema, and autoimmunity |
| Winged-helix nude (FOXN1) deficiency | AR | 601705 | 600838 | Congenital alopecia, and nail dystrophy, abnormal thymic epithelium |
| Purine nucleoside phosphorylase deficiency (PNP) | AR | 613179 | 164050 | Autoimmune hemolytic anemia, neurological impairment, and neoplasia |
| CD40 ligand deficiency | XL | 308230 | 300386 | Neutropenia, thrombocytopenia; hemolytic anemia, biliary tract and liver disease, lymphoproliferative disease, and increased rates of malignancy |
| CD40 deficiency | AR | 606843 | 109535 | Neutropenia, gastrointestinal and liver/biliary tract disease |
| Itk deficiency | AR | 613011 | 186973 | EBV- associated lymphoproliferation |
| Dedicator of cytokinesis 8 (DOCK8) deficiency | AR | 243700 | 611432 | Extensive cutaneous viral and bacterial infections, susceptibility to cancer, hypereosinophilia, severe atopy, low NK cells |
Abbreviations: SCID, severe combined immune deficiencies; XL, X-linked inheritance; AR, autosomal recessive inheritance; NK, natural killer cells; MHC, major histocompatibility complex; IPEX, immune dysregulation polyendocrinopathy enteropathy (X-linked); lck, lymphocyte-specific protein tyrosine kinase; ZAP70, zeta chain-associated 70-kDa protein kinase; FOXN1, forkhead box protein N1; Itk, IL-2-inducible T-cell kinase; EBV, Epstein–Barr virus.