Table 1.
MDS predisposition syndromes
| Hematologic abnormalities | Syndrome | Gene function | Gene | Inheritance |
|---|---|---|---|---|
| Marrow failure | Dyskeratosis congenita/telomere biology disorder | Disorders of telomere maintenance | DKC1 | X-linked |
| 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 | |||
| Fanconi anemia | DNA repair defect | FANCA | AR | |
| FANCB | X-linked | |||
| FANCC | AR | |||
| FANCD1/BRCA2 | AR | |||
| FANCD2 | AR | |||
| FANCE | 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 | |||
| FANCW/RFWD3 | AR | |||
| GATA2 spectrum disorders | Transcription factor | GATA2 | AD | |
| Shwachman-Diamond syndrome | Ribosomopathy | SBDS | AR | |
| EFL1 | AR | |||
| SDS-like | SRP54 | AD | ||
| DNAJC21 | AR | |||
| MIRAGE syndrome | Suppression of cell proliferation | SAMD9 | AD | |
| Ataxia-pancytopenia syndrome | SAMD9L | AD | ||
| Bone marrow failure syndrome 1 | Protein trafficking | SRP72 | AD | |
| Bone marrow failure syndrome 2 | Helicase | ERCC6L2 | AR | |
| Thrombocytopenia, platelet dysfunction | Thrombocytopenia 2 | Abnormal megakaryopoiesis | ANKRD26 | AD |
| Familial platelet disorder with propensity to myeloid malignancy | Transcription factor | RUNX1 | AD | |
| Thrombocytopenia 5 | ETV6 | AD | ||
| Red cell aplasia | Diamond-Blackfan anemia | Ribosomopathy | GATA1 | X-linked |
| RPL5 | AD | |||
| 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 | |||
| (TSR2) | X-linked | |||
| Neutropenia, cyclic neutropenia | Severe congenital neutropenia | Unfolded protein response, apoptosis | ELANE | AD |
| Neutropenia | Apoptosis, mitochondrial membrane potential | HAX1 | AR | |
| Transcriptional repressor | GFI1 | AD | ||
| Abnormal glucose metabolism | G6PC3 | AR | ||
| Abnormal glycosylation | JAGN1 | AR | ||
| X-linked neutropenia | Defect in mitosis and cytokinesis | WAS | X-linked | |
| Bloom syndrome | DNA repair defect in homologous recombination, chromosomal instability | BLM | AR | |
| Constitutional mismatch repair deficiency syndrome (Lynch syndrome) | DNA repair defect | MLH1 | AD | |
| MSH2 | AD | |||
| MSH6 | AD | |||
| PMS2 | AD | |||
| EPCAM | AD | |||
| Down syndrome | Chromosomal abnormality; trisomy 21 | Trisomy 21 | Variable | |
| EGFR family tyrosine kinase | ERBB3 | AD | ||
| Familial AML | Transcription factor | CEBPA | AD | |
| Li-Fraumeni syndrome | Germline p53 mutations, tumor suppressor | p53 | AD | |
| Ligase IV syndrome | DNA repair defect | LIG4 | AR | |
| MBD4 | 5mC deamination | MBD4 | AR | |
| Neurofibromatosis 1 | Ras pathway | NF1 | AD | |
| Nijmegen breakage syndrome | DNA repair defect, double-stranded DNA repair | NBN | AR | |
| Noonan syndrome Noonan-like | Ras pathway mutations | PTPN11 | AD | |
| Noonan-like | CBL | AD | ||
| Susceptibility to acute myeloid leukemia | Tumor suppressor | DDX41 | AD | |
| Trisomy 8 mosaicism | Chromosomal abnormality; trisomy 8 | Trisomy 8 | Variable | |
| Werner syndrome | DNA replication/repair defect, RecQ helicase | WRN | AR |
5mC, 5-methylcytosine; AD, autosomal dominant; AR, autosomal recessive; AML, acute myeloid leukemia; EGFR, epidermal growth factor receptor; MIRAGE, myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy; SDS, Shwachman-Diamond syndrome.