Table 1.
Genetic syndromes that predispose to pediatric ALL.
| Genes | Locus | Mode of inheritance | ALL Subtype | Other associated neoplasms | Reference | |
|---|---|---|---|---|---|---|
| DNA Damage Response and Cell Cycle/Apoptosis | ||||||
| Ataxia Telangiectasia (AT) | ATM | 11q22.3 | AR | T-ALL | T-PLL, NHL, HL, B-CLL, breast, ovarian, gastric, melanoma, leiomyomas, and sarcomas | [6] |
| Bloom syndrome (BS) | BLM | 15q26.1 | AR | ALL | MDS, AML, NHL, GI (upper/lower), GU, oropharyngeal, skin, breast | [7,110] |
| Constitutional mismatch repair deficiency syndrome (CMMRD) | MLH1 | 3p22.2 2p21-p16 | AR | B-ALL or T-ALL | NHL, AML, CML, GI, brain | [113–115] |
| MSH2 | 2p16.3 7p22.1 | |||||
| MSH6 | 2p21 | |||||
| PMS2 | ||||||
| EPCAM | ||||||
| Fanconi anemia (FA) | FANCA | 16q24.3 | AR | ALL | MDS, AML, squamous cell carcinoma of the head, neck, esophagus, and vulva, cervical cancer, liver tumors | [8] |
| FANCC | 9q22.32 | |||||
| FANCD2 | 3p25.3 | |||||
| BRCA2 | 13q13.1 | |||||
| FANCE | 6p21.31 | |||||
| FANCI | 15q26.1 | |||||
| FANCL | 2p16.1 | |||||
| RAD51C | 17q22 | |||||
| SLX4 | 16p13.3 | |||||
| ERCC4 | 16p13.12 | |||||
| UBE2T | 1q32.1 | |||||
| XRCC2 | 7q36.1 | |||||
| MAD2L2 | 1p36.22 | |||||
| RFWD3 | 16q23.1 | |||||
| FANCB | Xp22.2 | XLR | ||||
| RAD51A | 15q15.1 | AD | ||||
| FANCF | 11p14.3 | Unknown | ||||
| XRCC9 | 9p13.3 | |||||
| BRIP1 | 17q23.2 | |||||
| FANCM | 14q21.2 | |||||
| PALB2 | 16p12.2 | |||||
| Li-Fraumeni syndrome (LFS) | TP53 | 17p13.1 | AD | B-ALL | MDS, AML (therapy-associated), NHL, brain, bone, soft tissue, breast, adrenocortical carcinoma | [101–105] |
| Nijmegen breakage syndrome (NBS) | NBN | 8q21.3 | AR | T-ALL | NHL, AML, APL, medulloblastoma, glioma, RMS | [9] |
| Lymphocyte Differentiation | ||||||
| Familial platelet disorder with predisposition to myeloid malignancy (FPDMM) | RUNX1 | 21q22.12 | AD | T-ALL | AML | [79,84,85] |
| IKZF1-associated leukemia predisposition | IKZF1 | 7p12.2 | AD | B-ALL | None | [46] |
| PAX5-associated leukemia predisposition | PAX5 | 9p13.2 | AD | B-ALL | None | [19,20] |
| ETV6-associated leukemia predisposition | ETV6 | 12p13.2 | AD | B-ALL | AML, CML, NHL, MDS, multiple myeloma | [30,32–36] |
| Signaling | ||||||
| Neurofibromatosis, type 1 (NF1) | NF1 | 17q11.2 | AD | ALL | JMML, AML, brain, PNST, RMS, GIST, breast, pheochromocytoma | [69] |
| Noonan syndrome (NS) | PTPN11 | 12q24.13 | AD | ALL | JMML, CMML, AML, RMS, neuroblastoma | [51,53,54] |
AML, acute myeloid leukemia; APL, acute prolymphocytic leukemia; AT, Ataxia Telangiectasia; B-CLL, B cell chronic lymphocytic leukemia; BS, Bloom syndrome; CML, chronic myeloid leukemia; CMML, chronic myelomonocytic leukemia; CMMRD, Constitutional mismatch repair deficiency; FA, Fanconi anemia; FPDMM, Familial platelet disorder with predisposition to myeloid malignancies; GI, gastrointestinal; GIST, gastrointestinal stromal tumor; GU, genitourinary; HL, Hodgkin lymphoma; JMML, juvenile myelomonocytic leukemia; LFS, Li-Fraumeni syndrome; MDS, myelodysplastic syndrome; NBS, Nijmegen breakage syndrome; NF1, Neurofibromatosis type 1; NHL, Non-Hodgkin lymphoma; NS, Noonan syndrome; PNST, peripheral nerve sheath tumor; RMS, rhabdomyosarcoma; T-PLL, T cell prolymphocytic leukemia.