Table 1.
Genetic and clinical manifestations in VEO-IBD.
| GROUP | GENE DEFECT | CLINICAL PHENOTYPE | SPECIFIC TREATMENT |
|---|---|---|---|
| Epithelial Barrier Dysfunction | |||
| NEMO deficiency | IKBKG | Ectodermal dysplasia, antibody deficiency, enterocolitis | |
| ADAM17 deficiency | ADAM17 | Erythematous psoriasiform rash, dermatitis, enteropathy | |
| TTC7A deficiency | TTC7A | Intestinal atresia, enterocolitis, SCID | |
| Dystrophic epidermolysis bulls | COL7A1 | Dystrophic epidermolysis bulbosa, esophageal strictures, Crohn’s disease | |
| Kindler syndrome | FERMT1 | Skin blistering, atrophy, cancer, ulcerative colitis | |
| Loeys-Dietz syndrome | TGFBR1 and 2 | Skeletal abnormalities, craniofacial abnormalities, vascular injury, enterocolitis | |
| Congenital chloride diarrhea | SLC9A3 | Infantile diarrhea, enteropathy with electrolyte abnormalities | |
| Familial diarrhea | GUCY2 | Secretory diarrhea, enteropathy with electrolyte abnormalities | |
| Phagocytic Defects | |||
| Chronic Granulomatous Disease (CGD) | CYBB, CYBA, NCF1, NCF2, NCF4 | Severe bacterial and fungal infections throughout the body, fistulizing Crohn’s Disease with granulomas, intestinal obstruction, perianal abscesses | Anti-microbial prophylaxis, Anti-IL1 blockade, HCT |
| Leukocyte Adhesion deficiency (LAD1) | ITGB2 | Delayed separation of umbilical cord, infection, leukocytosis, enteropathy | Anti-microbial prophylaxis, HCT |
| T and B Defects | |||
| Severe Combined Immunodeficiency (SCID) | ARTEMIS, ZAP70,RAG1/2, IL2RG, ILRA7, LIG4, JACK3, ADA | Recurrent infections, variable enteropathy and enterocolitis | HCT |
| Omenn syndrome | IL7R | Diffuse erythroderma, lymphadenopathy, eosinophilia, cartilage and hair hypoplasia, hepatomegaly intestinal inflammation | HCT |
| CTLA-4 deficiency | CTLA4 | Type 1 diabetes, cytopenias, respiratory infections, enteropathy | Gammaglobulin, Abatacept, Sirolimus |
| ICOS deficiency | ICOS | CVID with recurrent viral and bacterial infections, splenomegaly, colitis | Gammaglobulin |
| Bruton’s or X-linked agammaglobulinemia | BTK | Sinusitis, acute otitis media, colitis | Gammaglobulin |
| Wiskott-Aldrich syndrome | WAS | Thrombocytopenia, eczema, eosinophilia, colitis | HCT |
| T regulatory cells and regulatory pathway defects | |||
| IPEX syndrome | FoxP3 | Type 1 diabetes, dermatitis, skin and respiratory infections, enteropathy, | Cyclosporin, Tacrolimus, Sirolimus, anti-TNF, HCT |
| IPEX-like syndrome | STAT1, STAT3, LRBA, IL2RA, | STAT1 and STAT3: enteropathy, severe viral and bacterial infections, and endocrinopathy. | JAK inhibitors, Sirolimus, HCT |
| LRBA: enteropathy, cytopenias, lymphadenopathy, and hepatosplenomegaly. | |||
| IL2RA: enteropathy, eczema, recurrent viral infections, and autoimmune anemia | |||
| IL-10 signaling defects | IL-10RA, IL-10RB | Colitis, folliculitis, perianal fistulas, B cell lymphoma, occasional arthritis | HCT |
| Hyperinflammatory and auto inflammatory defects | |||
| X-linked lymphoproliferative syndrome 2 | XIAP | Splenomegaly, hemophagocytic lymphohistiocytosis (HLH), fistulizing enteropathy | HCT |
| NLRC4 | NLRC4 | Infantile enterocolitis, autoinflammation | Anti-IL18 blockade |
| Mevalonate kinase deficiency | MVK | Episodic fevers, peritonitis, arthritis, bloody enterocolitis | Anti-IL1 blockade |
| NOD2 signaling defect | TRIM22 | Perianal fistulizing disease, enterocolitis |