Leukemia predisposition genes
| Disorder/syndrome and gene . | Inheritance . | Hematologic malignancy . | Additional malignancies . | Laboratory features . | Clinical features . |
|---|---|---|---|---|---|
| Fanconi anemia | |||||
| FANCA | AR | MDS, AML (ALL with FANCD1) | Squamous cell carcinomas of head/neck, GI tract, vulva; liver tumors; additional solid tumors associated with FANCD1 include brain tumors, Wilms tumor | BMF, chromosomal breakage, or cell cycle arrest with diepoxybutane or mitomycin C | Short stature, facial dysmorphisms, skin pigmentation, skeletal, thumb anomalies, renal, gonadal, CNS, cardiac, GI |
| FANCB | X linked | ||||
| FANCC | AR | ||||
| FANCD1/BRCA2 | AR | ||||
| FANCD2 | AR | ||||
| FANCDE | AR | ||||
| FANCF | AR | ||||
| FANCG | AR | ||||
| FANCI | AR | ||||
| FANCJ/BRIP1/BACH1 | AR | ||||
| FANCL | AR | ||||
| FANCM | AR | ||||
| FANCN/PALB2 | AR | ||||
| FANCO/RAD51C | AR | ||||
| FANCP/SLX4 | AR | ||||
| FANCQ/ERCC4 | AR | ||||
| FANCR/RAD51 | AD | ||||
| FANCS/BRCA1 | AR | ||||
| FANCT/UBE2T | AR | ||||
| FANCU/XRCC2 | AR | ||||
| FANCV/REV7 | AR | ||||
| Diamond-Blackfan anemia | |||||
| RPL5 | AD | MDS, AML | Osteosarcoma, soft tissue sarcomas | Anemia, bone marrow red cell aplasia, elevated erythrocyte adenosine deaminase | Thumb anomalies, short stature, facial dysmorphisms, cleft lip/palate, Pierre Robin syndrome, cardiac, GU |
| RPL11 | AD | ||||
| RPL15 | AD | ||||
| RPL23 | AD | ||||
| RPL26 | AD | ||||
| RPL27 | AD | ||||
| RPL31 | AD | ||||
| RPL35a | AD | ||||
| RPL36 | AD | ||||
| RPS7 | AD | ||||
| RPS10 | AD | ||||
| RPS15 | AD | ||||
| RPS17 | AD | ||||
| RPS19 | AD | ||||
| RPS24 | AD | ||||
| RPS26 | AD | ||||
| RPS27 | AD | ||||
| RPS27A | AD | ||||
| RPS28 | AD | ||||
| RPS29 | AD | ||||
| GATA1 | X linked | ||||
| TSR2 | X linked | ||||
| Dyskeratosis congenita | |||||
| DKC1 | X linked | MDS, AML | Squamous cell carcinomas of head/neck/GI tract | BMF, shortened telomere length, immunodeficiencies | Nail dystrophy, rash, leukoplakia, liver, short stature, pulmonary fibrosis, vascular anomalies, eyes, hair (early greying or loss), dental, CNS, GI, GU |
| TERC | AD | ||||
| TERT | AD, AR | ||||
| NOLA3/NOP10 | AR | ||||
| NOLA2/NHP2 | AR | ||||
| TINF2 | AD | ||||
| WRAP53/TCAB1 | AR | ||||
| CTC1 | AR | ||||
| RTEL1 | AD, AR | ||||
| ACD/TPP1 | AD, AR | ||||
| PARN | AD, AR | ||||
| NAF1 | AD | ||||
| STN1 | AD | ||||
| Shwachman-Diamond syndrome | |||||
| SBDS | AR | MDS, AML | — | BMF, low serum trypsinogen or pancreatic isoamylase | Steatorrhea, thoracic dysplasia, metaphyseal dysostosis, short stature |
| Severe congenital neutropenia | |||||
| ELANE | AD | MDS, AML | — | Neutropenia, bone marrow promyelocyte arrest | Neurological abnormalities |
| HAX1 | AR | ||||
| Familial MDS/AML with mutated GATA2 (Emberger syndrome, MonoMac syndrome) | |||||
| GATA2 | AD | MDS, AML | — | BMF, monocytopenia, cellular and humoral immunodeficiencies | Warts, atypical mycobacteria, lymphedema, deafness, pulmonary alveolar proteinosis, arterio-venous malformations |
| MIRAGE syndrome | |||||
| SAMD9 | AD | MDS, AML | — | Cytopenias, immunologic abnormalities | Short stature, adrenal hypoplasia, infections, CNS, GI, GU, skeletal |
| Ataxia-pancytopenia syndrome | |||||
| SAMD9L | AD | MDS, AML | — | BMF | Ataxia (variable) |
| Bone marrow failure syndrome 1 | |||||
| SRP72 | AD | MDS | — | BMF | Sensorineural hearing loss |
| Familial MDS/AML with mutated DDX41 | |||||
| DDX41 | AD | MDS, AML | — | — | — |
| Familial platelet disorder with propensity to myeloid malignancy | |||||
| RUNX1 | AD | MDS, AML, ALL | — | Thrombocytopenia, abnormal platelet function | — |
| Thrombocytopenia 2 | |||||
| ANKRD26 | AD | MDS, AML | — | Thrombocytopenia, abnormal platelet function | — |
| Thrombocytopenia 5 | |||||
| ETV6 | AD | ALL, MDS, AML | — | Thrombocytopenia, abnormal platelet function | — |
| Familial AML with CEBPA mutation | |||||
| CEBPA | AD | AML | — | — | — |
| Li-Fraumeni | |||||
| TP53 | AD | ALL, MDS, AML | Breast, soft tissue sarcoma, osteosarcoma, brain, adrenocortical carcinoma, lung, colon, pancreas, Wilms, prostate | — | — |
| Susceptibility to ALL3 | |||||
| PAX5 | AD | ALL | — | — | — |
| Constitutional mismatch repair deficiency syndrome | |||||
| MLH1 | AR | Lymphoma, ALL, AML | CNS, GI tract, other | — | Café-au-lait spots, axillary freckling, Lisch nodules, neurofibromas, intestinal adenomas |
| MSH2 | AR | ||||
| MSH6 | AR | ||||
| TPMS2 | AR |
| Disorder/syndrome and gene . | Inheritance . | Hematologic malignancy . | Additional malignancies . | Laboratory features . | Clinical features . |
|---|---|---|---|---|---|
| Fanconi anemia | |||||
| FANCA | AR | MDS, AML (ALL with FANCD1) | Squamous cell carcinomas of head/neck, GI tract, vulva; liver tumors; additional solid tumors associated with FANCD1 include brain tumors, Wilms tumor | BMF, chromosomal breakage, or cell cycle arrest with diepoxybutane or mitomycin C | Short stature, facial dysmorphisms, skin pigmentation, skeletal, thumb anomalies, renal, gonadal, CNS, cardiac, GI |
| FANCB | X linked | ||||
| FANCC | AR | ||||
| FANCD1/BRCA2 | AR | ||||
| FANCD2 | AR | ||||
| FANCDE | AR | ||||
| FANCF | AR | ||||
| FANCG | AR | ||||
| FANCI | AR | ||||
| FANCJ/BRIP1/BACH1 | AR | ||||
| FANCL | AR | ||||
| FANCM | AR | ||||
| FANCN/PALB2 | AR | ||||
| FANCO/RAD51C | AR | ||||
| FANCP/SLX4 | AR | ||||
| FANCQ/ERCC4 | AR | ||||
| FANCR/RAD51 | AD | ||||
| FANCS/BRCA1 | AR | ||||
| FANCT/UBE2T | AR | ||||
| FANCU/XRCC2 | AR | ||||
| FANCV/REV7 | AR | ||||
| Diamond-Blackfan anemia | |||||
| RPL5 | AD | MDS, AML | Osteosarcoma, soft tissue sarcomas | Anemia, bone marrow red cell aplasia, elevated erythrocyte adenosine deaminase | Thumb anomalies, short stature, facial dysmorphisms, cleft lip/palate, Pierre Robin syndrome, cardiac, GU |
| RPL11 | AD | ||||
| RPL15 | AD | ||||
| RPL23 | AD | ||||
| RPL26 | AD | ||||
| RPL27 | AD | ||||
| RPL31 | AD | ||||
| RPL35a | AD | ||||
| RPL36 | AD | ||||
| RPS7 | AD | ||||
| RPS10 | AD | ||||
| RPS15 | AD | ||||
| RPS17 | AD | ||||
| RPS19 | AD | ||||
| RPS24 | AD | ||||
| RPS26 | AD | ||||
| RPS27 | AD | ||||
| RPS27A | AD | ||||
| RPS28 | AD | ||||
| RPS29 | AD | ||||
| GATA1 | X linked | ||||
| TSR2 | X linked | ||||
| Dyskeratosis congenita | |||||
| DKC1 | X linked | MDS, AML | Squamous cell carcinomas of head/neck/GI tract | BMF, shortened telomere length, immunodeficiencies | Nail dystrophy, rash, leukoplakia, liver, short stature, pulmonary fibrosis, vascular anomalies, eyes, hair (early greying or loss), dental, CNS, GI, GU |
| TERC | AD | ||||
| TERT | AD, AR | ||||
| NOLA3/NOP10 | AR | ||||
| NOLA2/NHP2 | AR | ||||
| TINF2 | AD | ||||
| WRAP53/TCAB1 | AR | ||||
| CTC1 | AR | ||||
| RTEL1 | AD, AR | ||||
| ACD/TPP1 | AD, AR | ||||
| PARN | AD, AR | ||||
| NAF1 | AD | ||||
| STN1 | AD | ||||
| Shwachman-Diamond syndrome | |||||
| SBDS | AR | MDS, AML | — | BMF, low serum trypsinogen or pancreatic isoamylase | Steatorrhea, thoracic dysplasia, metaphyseal dysostosis, short stature |
| Severe congenital neutropenia | |||||
| ELANE | AD | MDS, AML | — | Neutropenia, bone marrow promyelocyte arrest | Neurological abnormalities |
| HAX1 | AR | ||||
| Familial MDS/AML with mutated GATA2 (Emberger syndrome, MonoMac syndrome) | |||||
| GATA2 | AD | MDS, AML | — | BMF, monocytopenia, cellular and humoral immunodeficiencies | Warts, atypical mycobacteria, lymphedema, deafness, pulmonary alveolar proteinosis, arterio-venous malformations |
| MIRAGE syndrome | |||||
| SAMD9 | AD | MDS, AML | — | Cytopenias, immunologic abnormalities | Short stature, adrenal hypoplasia, infections, CNS, GI, GU, skeletal |
| Ataxia-pancytopenia syndrome | |||||
| SAMD9L | AD | MDS, AML | — | BMF | Ataxia (variable) |
| Bone marrow failure syndrome 1 | |||||
| SRP72 | AD | MDS | — | BMF | Sensorineural hearing loss |
| Familial MDS/AML with mutated DDX41 | |||||
| DDX41 | AD | MDS, AML | — | — | — |
| Familial platelet disorder with propensity to myeloid malignancy | |||||
| RUNX1 | AD | MDS, AML, ALL | — | Thrombocytopenia, abnormal platelet function | — |
| Thrombocytopenia 2 | |||||
| ANKRD26 | AD | MDS, AML | — | Thrombocytopenia, abnormal platelet function | — |
| Thrombocytopenia 5 | |||||
| ETV6 | AD | ALL, MDS, AML | — | Thrombocytopenia, abnormal platelet function | — |
| Familial AML with CEBPA mutation | |||||
| CEBPA | AD | AML | — | — | — |
| Li-Fraumeni | |||||
| TP53 | AD | ALL, MDS, AML | Breast, soft tissue sarcoma, osteosarcoma, brain, adrenocortical carcinoma, lung, colon, pancreas, Wilms, prostate | — | — |
| Susceptibility to ALL3 | |||||
| PAX5 | AD | ALL | — | — | — |
| Constitutional mismatch repair deficiency syndrome | |||||
| MLH1 | AR | Lymphoma, ALL, AML | CNS, GI tract, other | — | Café-au-lait spots, axillary freckling, Lisch nodules, neurofibromas, intestinal adenomas |
| MSH2 | AR | ||||
| MSH6 | AR | ||||
| TPMS2 | AR |
Space limitations preclude a comprehensive listing of genes and associated features.
AD, autosomal dominant; ALL, acute lymphoblastic leukemia; AR, autosomal recessive; BMF, bone marrow failure; CNS, central nervous system; GI, gastrointestinal; GU, genitourinary; MDS, myelodysplastic syndrome.