Summary of familial hematologic cancer syndromes1,7,12,13,15,17
| Condition . | Gene name . | Hematologic cancer . | Nonmalignant hematologic features . | Other cancer risks . | Cancer screening for at-risk family members . |
|---|---|---|---|---|---|
| Fanconi anemia | FANC1, FANCB, FANCC, BRCA2, FANCD2, FANCE, FANCF, FANCG, FANCI, BRIP1, FANCL, FANCM, PALB2, RAD51C, SLX4 | MDS/AML | Bone marrow failure | Head/neck and anogenital squamous cell cancers, liver cancer, esophageal cancer | CBC every 2 to 3 mo, bone marrow biopsy, annual gynecologic examination, oral cancer screening (at least annually), consider endoscopic examination of esophagus |
| Dyskeratosis congenita | CTC, DKC1, TERC, TERT, TINF2, NHP2, POP10, WRAP53 | MDS/AML | Bone marrow failure, macrocytosis | Skin, head/neck, and anogenital squamous cell cancers | Annual CBC and bone marrow biopsy, dermatology examination, annual gynecologic examination, oral cancer screening (at least annually) |
| Familial AML with mutated CEBPA | CEBPA | AML | None | No other known cancer risks | No consensus; limited studies; consider periodic CBC, including baseline bone marrow biopsy |
| Familial AML with mutated GATA2 | GATA2 | AML/MDS | Monocytopenia and mycobacterial infection syndrome, Emberger syndrome, immune deficiencies | No other known cancer risks | No consensus; limited studies; consider periodic CBC, including baseline bone marrow biopsy |
| Quantitative and qualitative platelet disorders with propensity to myeloid malignancy | RUNX1, ANKRD26, ETV6 | AML/MDS | Thrombocytopenia | No other known cancer risks | No consensus; limited studies; consider periodic CBC, including baseline bone marrow biopsy |
| DDX41-related AML | DDX41 | AML/MDS (late onset), possibly others | No | No other known cancer risks | No consensus; consider periodic CBC |
| Familial mosaic monosomy 7 | Monosomy of chromosome 7 | AML/MDS | Bone marrow insufficiency, anemia | No other known cancer risks | Annual CBC, karyotype, and hemoglobin F |
| Familial aplastic anemia/MDS related to SRP72 | SRP72 | MDS | Aplastic anemia | No other known cancer risks | No consensus; consider periodic CBC |
| SH2B3-related familial ALL | SH2B3 | ALL | Autoimmunity | No other known cancer risks | No consensus; consider periodic CBC |
| PAX5-related familial ALL | PAX5 | ALL | No | No other known cancer risks | No consensus; consider periodic CBC |
| Li-Fraumeni syndrome | TP53 | ALL, AML, MDS | No | Adrenal, breast, brain, and lung sarcoma, gastrointestinal cancers | Breast imaging every 6 mo, annual total body and brain magnetic resonance imaging scan, colonoscopy every 2 to 5 y; consider periodic CBC for hematologic cancer screening |
| Constitutional mismatch repair deficiency | MSH2, MLH1, MSH6, PMS2 | ALL/AML | No | Brain tumors, gastrointestinal cancers |
| Condition . | Gene name . | Hematologic cancer . | Nonmalignant hematologic features . | Other cancer risks . | Cancer screening for at-risk family members . |
|---|---|---|---|---|---|
| Fanconi anemia | FANC1, FANCB, FANCC, BRCA2, FANCD2, FANCE, FANCF, FANCG, FANCI, BRIP1, FANCL, FANCM, PALB2, RAD51C, SLX4 | MDS/AML | Bone marrow failure | Head/neck and anogenital squamous cell cancers, liver cancer, esophageal cancer | CBC every 2 to 3 mo, bone marrow biopsy, annual gynecologic examination, oral cancer screening (at least annually), consider endoscopic examination of esophagus |
| Dyskeratosis congenita | CTC, DKC1, TERC, TERT, TINF2, NHP2, POP10, WRAP53 | MDS/AML | Bone marrow failure, macrocytosis | Skin, head/neck, and anogenital squamous cell cancers | Annual CBC and bone marrow biopsy, dermatology examination, annual gynecologic examination, oral cancer screening (at least annually) |
| Familial AML with mutated CEBPA | CEBPA | AML | None | No other known cancer risks | No consensus; limited studies; consider periodic CBC, including baseline bone marrow biopsy |
| Familial AML with mutated GATA2 | GATA2 | AML/MDS | Monocytopenia and mycobacterial infection syndrome, Emberger syndrome, immune deficiencies | No other known cancer risks | No consensus; limited studies; consider periodic CBC, including baseline bone marrow biopsy |
| Quantitative and qualitative platelet disorders with propensity to myeloid malignancy | RUNX1, ANKRD26, ETV6 | AML/MDS | Thrombocytopenia | No other known cancer risks | No consensus; limited studies; consider periodic CBC, including baseline bone marrow biopsy |
| DDX41-related AML | DDX41 | AML/MDS (late onset), possibly others | No | No other known cancer risks | No consensus; consider periodic CBC |
| Familial mosaic monosomy 7 | Monosomy of chromosome 7 | AML/MDS | Bone marrow insufficiency, anemia | No other known cancer risks | Annual CBC, karyotype, and hemoglobin F |
| Familial aplastic anemia/MDS related to SRP72 | SRP72 | MDS | Aplastic anemia | No other known cancer risks | No consensus; consider periodic CBC |
| SH2B3-related familial ALL | SH2B3 | ALL | Autoimmunity | No other known cancer risks | No consensus; consider periodic CBC |
| PAX5-related familial ALL | PAX5 | ALL | No | No other known cancer risks | No consensus; consider periodic CBC |
| Li-Fraumeni syndrome | TP53 | ALL, AML, MDS | No | Adrenal, breast, brain, and lung sarcoma, gastrointestinal cancers | Breast imaging every 6 mo, annual total body and brain magnetic resonance imaging scan, colonoscopy every 2 to 5 y; consider periodic CBC for hematologic cancer screening |
| Constitutional mismatch repair deficiency | MSH2, MLH1, MSH6, PMS2 | ALL/AML | No | Brain tumors, gastrointestinal cancers |