Table 2.
Main clinical features of patients with relevant genetic findings.
| ID | Sex | Age at study (y) | Gene | Family history | Consanguinity | Age of onset (y) | Syndromic features | Infections | Autoimmunity | Lymphoproliferation | Inflammation | Main clinical features, key words | Treatment |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PATIENTS WITH MUTATIONS IN PID GENES (2017 IUIS CLASSIFICATION) | |||||||||||||
| P1 | M | 15 | PIK3R1 | – | – | 7 | – | V | – | Malign | Gut | IgA deficiency, immune dysregulation, growth delay, enteropathy, intestinal large bowel lymphoma | IVIG, immunosuppression (rapamycin and rituximab) |
| P2 | F | 57 | TNFRSF13B | – | – | 14 | – | B | – | Benign | Gut, lung | CVID, infections, GLILD, granulomas, adenopathies, pancytopenia | IVIG, immunosuppression (rituximab, corticoids, azathioprine), antibiotics |
| P3 | F | 8 | TNFRSF13B | √ | – | 3 | – | B, V | √ | Benign | – | EBV, pancytopenia, hepatosplenomegaly, hypogammaglobulinemia, ALPS-like, CVID-like | IVIG, rapamycin |
| P4 | M | 18 | IKBKG | √ | – | 14 | – | – | – | – | Gut, joints | Crohn's disease, joint affectation, CGD, NEMO deficiency | Infliximab |
| P5 | F | 10 | STAT3 | – | – | 4 | √ | B, F, Myc | – | – | – | Hyper IgE, atypical mycobacteria | Antifungal prophylaxis, vitamin D, IVIG, antibiotics |
| P6 | M | 2 | XIAP | – | √ | 0.8 | √ | B | – | – | Gut | Enteropathy, bacterial infection, growth delay | IVIG, patient died |
| P7 | M | 1 | G6PD | – | – | 0.3 | – | B | – | – | Bone | Osteomyelitis, Salmonella spp. | - |
| P8 | M | 30 | STAT1 | – | – | 0.0 | – | F | √ | – | Skin, mucosa | Dermatophytosis, oral candidiasis | Antifungal prophylaxis, |
| P9 | F | 4 | STAT1 | – | – | 0.8 | – | F | – | – | Joints | CMC, polyarthritis, episcleritis, bronchiectasis | Ruxolitinib, HSCT |
| P10 | M | 6 | STAT1 | √ | √ | 4 | – | F | – | – | – | Familial CMC | Antifungal prophylaxis |
| P11 | F | 12 | PLCG2 | – | – | 0.8 | √ | B | – | – | Skin, lungs | Agammaglobulinemia, severe cutaneous inflammation, bronchiectasis, B cell lymphopenia, growth delay | IVIG, antibiotics, corticosteroids, etanercept, anakinra |
| P12 | M | 15 | ADA | – | – | 8 | – | B | – | Malign | – | Hodgkin lymphoma, B cell deficiency | Chemotherapy |
| PATIENTS WITH MUTATIONS IN GENES NOT INCLUDED IN THE PID CLASSIFICATION | |||||||||||||
| P13 | M | 5 | SKIV2L | – | – | 0.8 | √ | B | – | – | Gut | Inflammatory enteropathy, growth delay | Antibiotics, IVIG, adalimumab, immunosuppression (azathioprine, prednisone, rapamycin) |
| P14 | M | 0.25 | MMACHC | √ | – | 0.1 | – | – | – | – | – | fHLH, XLP | Died before diagnosis |
| P15 | F | 44 | SLC27A4 | – | √ | n.a. | – | – | – | – | Skin | Netherton syndrome | - |
| P16 | F | 0.3 | DSG1 | – | – | 0.3 | – | B | – | – | – | Erythroderma, Netherton syndrome, hyper IgE, eosinophilia | Infliximab, adalimumab, cyclosporine |
| P17 | F | 1 | DNAI2 | √ | √ | 0.1 | – | V, F | √ | Malign | – | Recurrent bronchitis, biphenotypic leukemia, growth delay | HSCT (due to leukemia) |
| P18 | M | 38 | SIX6 | √ | √ | n.a. | – | B | – | – | – | CID, Low IgA | IVIG |
| P19 | M | 5 | RECQL4 | – | √ | 1 | √ | V, F | – | – | – | CVID, growth delay | IVIG, antibiotic prophylaxis |
| PATIENTS WITH INCOMPLETE GENOTYPES/VARIANTS OF UNCERTAIN SIGNIFICATE (VUS) | |||||||||||||
| P20 | M | 11 | UNC13D | √ | – | 8 | – | V | – | Malign | Gut | Pancytopenia, hepatosplenomegaly, hemophagocytosis, panniculitic T cell lymphoma | HSCT (due to T cell lymphoma) |
| P21 | M | 13 | RAG2 | √ | – | 6 | √ | – | – | Benign | Systemic | Persistent fever, intermittent abdominal pain, granulomatous hepatitis | Immunosuppression (methotrexate + colchicine + corticosteroids) |
| P22 | M | 4 | PLCG2 | √ | √ | 1 | – | V | – | – | Skin | Periodic fever, skin rash | - |
| P23 | F | 11 | TRAF3 | – | – | 11 | – | V | – | – | – | Herpes Zoster, VZV meningoencephalitis | - |
| P24 | M | 2 | NOD2 | – | – | 0.6 | – | – | – | – | Gut | Early-onset colitis | - |
| PATIENTS WITH GENETIC FINDINGS POST-CLINICAL EXOME | |||||||||||||
| P25 | F | 8 | LRBA | √ | – | 0.7 | – | B, V, F | √ | Malign | Gut | EBV, lymphoproliferation, autoimmunity, infections, dysregulation, enteropathy, autoimmune cytopenia | IVIG, rapamycin, antibiotic prophylaxis, HSCT |
| P26 | F | 11 | LRBA | – | – | 2 | – | V | √ | Benign | – | ALPS | IVIG, abatacept |
| P27 | F | 7 | LRBA | – | – | 7 | – | B | √ | Benign | – | Antibody deficiency, autoimmunity, lymphoproliferative syndrome | IVIG, abatacept |
| P28 | F | 14 | IKZF1 | √ | – | 5 | √ | B | – | – | – | Agammaglobulinemia, neurological delay | IVIG |
| P29 | M | 9 | 13 Mb del cr.6 | √ | √ | 0.0 | √ | B, V | – | – | – | Neutrophilic dermatosis, oral and genital aphthae, growth delay | Etanercept |
| P30 | M | 6 | BTK | – | – | 4 | – | B | – | – | – | Pneumonia, hypogammaglobulinemia, absence of B cells | IVIG |
| P31 | M | 25 | Gorham-Staut disease | – | – | 21 | √ | B | – | – | Joints | Osteopenia, chylothorax, lymphopenia, S.Aureus bacteremia, septic arthritis | - |
n.a., not available; –, no; V, virus; B, bacteria; F, fungi; Myc, mycobacteria; ALPS, autoimmune lymphoproliferative syndrome; CID, combined immunodeficiency; CGD, chronic granulomatous disease; CMC, chronic mucocutaneous candidiasis; CVID, common variable immunodeficiency; EBV, Epstein-Barr virus; fHLH, familial hemophagocytic lymphohistiocytosis; GLILD, granulomatous and lymphocytic interstitial lung disease; HSCT, hematopoietic stem cell transplant; IVIG, intravenous immunoglobulin; VZV, varicella-zoster virus; XLP, X-linked lymphoproliferation. √, The patient presents this feature.