Version May 2024
| Name of syndrome | Causative gene(s) | Pattern of inheritance | Characteristic hematologic malignancies | Other hematopoietic abnormalities | Susceptibility to other malignancies | Other organ systems affected | CLIA-approved testing available | Recommended diagnostic test |
| Familial AML with mutated CEBPA (OMIM 116897) | CEBPA | AD | AML | None | None | None | Yes | CEBPA exon sequencing and gene rearrangement testing |
| Familial AML with mutated DDX41 | DDX41 | AD | MDS/AML, CMML | Monocytosis | Lymphoid malignancies Solid tumors (eg, colon, gastric, breast, pancreatic, bladder, melanoma) have also been reported but not yet definitively proven to be part of this syndrome. | None | Yes | DDX41 exon sequencing and gene rearrangement testing |
| Familial AML with mutated MBD4 | MBD4 | AD | AML | None | Possible associations: Colon polyps and potentially colorectal cancer | Colon polyps | Yes | MBD4 exon sequencing and gene rearrangement testing; may be suspected by the spectrum of tumor mutations. |
| Familial platelet disorder with propensity to myeloid malignancies (OMIM 601399) | RUNX1 | AD | MDS/AML/T cell ALL | Thrombocytopenia (mild to moderate); bleeding propensity due to aspirin-like platelet dysfunction | Eczema | None | Yes | RUNX1 exon sequencing and gene rearrangement testing |
| Thrombocytopenia 2 (OMIM 188000) | ANKRD26 | AD | MDS/AML | Thrombocytopenia (moderate); bleeding propensity due to platelet dysfunction | None | None | Yes | 5'UTR and exon sequencing of ANKRD26 |
| Thrombocytopenia 5 (OMIM 616216) | ETV6 | AD | MDS/AML, CMML, B cell ALL, multiple myeloma | Thrombocytopenia (moderate); platelet dysfunction | Unclear | None | Yes | ETV6 exon sequencing and gene rearrangement testing |
| Familial MDS/AML with mutated GATA2 (OMIM 137295) | GATA2 | AD | MDS/AML/CMML | None or Monocytopenia, NK cell, dendritic cell, B cell, and/or CD4+ T cell lymphopenia | None | Sensorineural deafness, immunodeficiency, cutaneous warts. MonoMAC syndrome (eg, pulmonary alveolar proteinosis; monocytopenia, NK cell-, dendritic cell-, and B cell- lymphopenia; disseminated atypical mycobacterial, viral, fungal infections). Emberger Syndrome: (eg, primary lymphedema; low CD4/CD8 ratio; cutaneous warts; sensorineural deafness) | Yes | GATA2 exon sequencing, intron 5 enhancer region sequencing, and gene rearrangement testing |
| Congenital SAMD9/SAMD9L mutations | SAMD9 and SAMD9L | AD | Monosomy 7 MDS/AML | Transient monosomy 7 and pancytopenia | None | Homozygous SAMD9 deletions are associated with normophosphatemic familial tumoral calcinosis. Heterozygous SAMD9 mutations are associated with MIRAGE syndrome: adrenal hypoplasia, growth retardation, genital abnormalities, and enteropathy. Heterozygous SAMD9L mutations are associated with ataxia. | Yes | Full gene sequencing of SAMD9 and SAMD9L and gene rearrangement testing for both genes. Note the possibility of loss of the germline allele along with monosomy 7; strongly consider use of a non-hematopoietic tissue for germline testing. |
| Familial aplastic anemia/MDS with SRP72 mutation (OMIM 602122) | SRP72 | AD | MDS | Aplastic anemia | None | Deafness | Yes | SRP72 exon sequencing and gene rearrangement testing |
| Myeloid neoplasms with germline predisposition due to 14q32 region duplications | 14q32 region duplications | AD | AML, MDS, ET, PV, PMF, CMML | Myelofibrosis | None | None | Yes | SNP array or specially designed NGS assay |
| Telomere syndromes (TS) due to mutation in TERC (OMIM 127550) or TERT (OMIM 187270) or RTEL1 (OMIM 615190) | TERC/TERT | AD AR (TERT) | MDS/AML | Macrocytosis; mild to moderate single or multiple cytopenias; aplastic anemia | Squamous cell carcinomas of the head/neck and anogenital regions | Autosomal dominant TS (eg, idiopathic pulmonary fibrosis, idiopathic hepatic fibrosis). Autosomal recessive or X-linked recessive TS (eg, nail dystrophy, oral leukoplakia, skin hypo- or hyper-pigmentation, premature gray hair, dental caries, hepatic cirrhosis, pulmonary fibrosis) Severe forms may manifest cerebellar hypoplasia, immunodeficiency, and/or developmental delay | Yes | Full gene sequencing and large rearrangement testing of TERT, TERC, RTEL1, and other telomere associated genes Telomere length studies of lymphocyte subsets via flow FISH can also be performed to aid in diagnosis in conjunction with genetic testing and the clinical picture |
| MECOM-associated syndrome (OMIM 165215 and 616738) | MECOM/EVI1 complex | AD | MDS | Bone marrow failure/B cell deficiency | None | Radioulnar synostosis, clinodactyly, cardiac/renal malformations, presenile hearing loss | Yes | MECOM/EVI1 complex exon sequencing and genomic rearrangement testing |
| Familial ALL due to TP53 mutation: rare Li Fraumeni syndrome presentation (OMIM 151623) | TP53 | AD | Familial ALL, especially hypodiploid | None | None | Breast cancer, sarcomas, malignant brain tumors, adrenocortical carcinomas | Yes | TP53 exon sequencing and gene rearrangement testing |
| Familial B cell ALL due to PAX5 mutation (OMIM 615545) | PAX5 | AD | Familial ALL, especially with ALL with 9p loss | None | None | None | Yes | PAX5 exon sequencing and gene rearrangement testing |
| Germline SH2B3 mutation (OMIM 605093) | SH2B3 | AR | Familial ALL | None | None | Developmental delay, autoimmunity, chronic hepatitis | Yes | SH2B3 exon sequencing and gene rearrangement testing |
| Familial B cell ALL due to IKZF1 mutation (OMIM 613067 and 603023) | IKZF1 | AD | Familial ALL | T cell, B cell, myeloid immunodeficiency | None | None | Yes | IKZF1 gene sequencing and gene rearrangement testing |
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