Table 1.
Inherited Syndromes Predisposing to Adult-Onset Hematologic Malignancy
| Syndrome | Gene | Inheritance | Hematologic Malignancy Risk | Other hematologic abnormalities | Non-hematologic complications |
|---|---|---|---|---|---|
| Familial platelet disorder with propensity to myeloid malignancies | RUNX1 | AD | MDS/AML/T-cell ALL | Thrombocytopenia, bleeding propensity, aspirin-like platelet dysfunction | Eczema |
| Thrombocytopenia 2 | ANKRD26 | AD | MDS/AML | Thrombocytopenia, bleeding propensity | None described |
| Familial AML with mutated CEBPA | CEBPA | AD | AML | None | None described |
| Familial AML with mutated DDX41 | DDX41 | AD | MDS/AML, CMML | None | None described |
| Thrombocytopenia 5 | ETV6 | AD | MDS/AML, CMML, B-cell ALL, multiple myeloma | Thrombocytopenia | Possible risk for solid tumors |
| Familial MDS/AML with mutated GATA2 | GATA2 | AD | MDS/AML/CMML | None or Neutropenia, monocytopenia (MonoMAC syndrome) | Lymphedema, sensorineural hearing loss, extra-genital warts, other |
| Telomere syndromes (dyskeratosis congenita) | TERC,TERT 1CTC1, DKC1, NHP2, NOP10, RTEL1, TINF2, WRAP53, ACD, PARN | AD, AR | MDS/AML | Macrocytosis, aplastic anemia | Pulmonary, hepatic fibrosis; head, neck, ano-genital SCC |
| Familial aplastic anemia with SRP72 mutation | SRP72 | AD | MDS | Aplastic anemia | Hearing loss |
| Familial B- cell ALL with PAX5 mutation | PAX5 | AD | ALL | None | None described |
| Germline SH2B3 | SH2B3 | AR | ALL | None | None described |
| Li-Fraumeni syndrome | TP53 | AD | ALL (esp hypodiploid cytogenetics), therapy-related myeloid disorders | None | Multiple solid tumors (breast, sarcoma, brain) |
| Fanconi anemia2 | FANCA, FANCB, FANCC, BRCA2, FANCD2, FANCE, FANCF, FANCG, FANCI, BRIP1, FANCL, FANCM, PALB2, RAD51C, SLX4 | AR | MDS/AML | Aplastic anemia | Head, neck, anogenital SCC, developmental delay, skeletal and renal anomalies |
AD=autosomal dominant, AR=autosomal recessive, MDS=myelodysplastic syndrome, AML=acute myeloid leukemia, ALL=acute lymphoblastic leukemia, CMML=chronic myelomonocytic leukemia, SCC=squamous cell carcinoma
1
These DC genes are typically diagnosed in infants/children with DC
2
The majority of individuals with Fanconi anemia are diagnosed in childhood; however, 10% of patients lack classic birth defects and present in adulthood