Inheritance and common clinical findings of inherited BMF syndromes
| . | Fanconi anemia37 . | Telomere biology disorders1 . | Shwachman Diamond syndrome38 . | Diamond Blackfan anemia39 . | GATA2 . | SAMD9/9L28 . | Platelet disorders24 . | MECOM- associated disorders25 . | ERCC6L22,40 . | DADA241 . |
|---|---|---|---|---|---|---|---|---|---|---|
| Affected genes | FANC genes, BRCA2 | DKC1, TERT, TERC, PARN, RTEL1, TINF2, CTC + others | SBDS, DNAJC21, and others | RP genes, TSR2, GATA1 | GATA2 | SAMD9/SAMD9L | c-MPL (CAMT) RBM8A (TAR) RUNX1, ETV6, ANKRD26, and others | MECOM (MDS1 and EVI1 complex locus) | ERCC6L2 | ADA2 |
| Inheritance | AR except for FANCB (XLR) and FANCR (AD) | AD: TERT, TERC, TINF2, RTEL1, PARN AR: CTC, RTEL1 XLR: DKC1 | AR | AD, XLR or sporadic | AD | AD | AR: (CAMT, TAR) AD: RUNX1, ETV6, ANKRD26 | AD | AR | AR |
| Common non hematologic clinic findings | - Limb abnormalities (absent radii/short thumbs) - Short stature - Renal anatomical defects - Café au lait spots - Microcephaly/ Microphthalmia | - DC triad: oral leukoplakia, dyskeratotic nails, reticulated skin - Pulmonary fibrosis - Liver disease (fibrosis, fatty liver) - AVM - Early grey hair - Immunodeficiency - Osteoporosis | - Failure to thrive/poor feeding - Steatorrhea - Recurrent infections - Skeletal abnormalities - Hepatomegaly - Intellectual disability - Congenital cardiac defects - Endocrinopathy | - Short stature/IUGR - Limb abnormalities (thumb) - Cardiac defects (VSD, ASD) - Cephalic malformation (microcephaly) - Developmental delay | - Immuno-deficiency (atypical mycobacteria, recurrent warts from HPV) - Lymphedema - Thrombosis - Pulmonary alveolar proteinosis (dyspnea and cough) | - MIRAGE: myelodysplasia, infection, growth restriction, adrenal hypoplasia, genital problems, enteropathy - Ataxia Pancytopenia: cerebellar symptoms and pancytopenia - SAAD: nodular neutrophilic panniculitis, ILD, basal ganglia calcifications, cytopenia | - CAMT: some neurological associations, possibly related to ICH - TAR: skeletal defects (absent radii), cow's milk intolerance, renal tract abnormalities, cardiac defects) - RUNX1: platelet function defect | - Radioulnar stenosis - Clinodactyly - Hearing loss - Cardiac malformations - Renal malformations | - Microcephaly - Developmental delay | - Strokes - Vasculitis - Systemic inflammation - Hypogammaglobulinemia |
| Malignancy risk | - MDS/AML - SCC of skin, head/neck, anogenital | - MDS/AML - SCC skin, head/neck, anogenital - BCC skin | MDS/AML | - MDS/AML - Colon cancer - Osteogenic sarcoma | - MDS/AML - SCC skin, anogenital - BCC skin | MDS/AML | - RUNX1/ETV6/ ANKRD26: MDS/AML or ALL - ALL > ETV6, MDS/AML > RUNX1/ANKRD26 | MDS/AML | MDS | None known |
| . | Fanconi anemia37 . | Telomere biology disorders1 . | Shwachman Diamond syndrome38 . | Diamond Blackfan anemia39 . | GATA2 . | SAMD9/9L28 . | Platelet disorders24 . | MECOM- associated disorders25 . | ERCC6L22,40 . | DADA241 . |
|---|---|---|---|---|---|---|---|---|---|---|
| Affected genes | FANC genes, BRCA2 | DKC1, TERT, TERC, PARN, RTEL1, TINF2, CTC + others | SBDS, DNAJC21, and others | RP genes, TSR2, GATA1 | GATA2 | SAMD9/SAMD9L | c-MPL (CAMT) RBM8A (TAR) RUNX1, ETV6, ANKRD26, and others | MECOM (MDS1 and EVI1 complex locus) | ERCC6L2 | ADA2 |
| Inheritance | AR except for FANCB (XLR) and FANCR (AD) | AD: TERT, TERC, TINF2, RTEL1, PARN AR: CTC, RTEL1 XLR: DKC1 | AR | AD, XLR or sporadic | AD | AD | AR: (CAMT, TAR) AD: RUNX1, ETV6, ANKRD26 | AD | AR | AR |
| Common non hematologic clinic findings | - Limb abnormalities (absent radii/short thumbs) - Short stature - Renal anatomical defects - Café au lait spots - Microcephaly/ Microphthalmia | - DC triad: oral leukoplakia, dyskeratotic nails, reticulated skin - Pulmonary fibrosis - Liver disease (fibrosis, fatty liver) - AVM - Early grey hair - Immunodeficiency - Osteoporosis | - Failure to thrive/poor feeding - Steatorrhea - Recurrent infections - Skeletal abnormalities - Hepatomegaly - Intellectual disability - Congenital cardiac defects - Endocrinopathy | - Short stature/IUGR - Limb abnormalities (thumb) - Cardiac defects (VSD, ASD) - Cephalic malformation (microcephaly) - Developmental delay | - Immuno-deficiency (atypical mycobacteria, recurrent warts from HPV) - Lymphedema - Thrombosis - Pulmonary alveolar proteinosis (dyspnea and cough) | - MIRAGE: myelodysplasia, infection, growth restriction, adrenal hypoplasia, genital problems, enteropathy - Ataxia Pancytopenia: cerebellar symptoms and pancytopenia - SAAD: nodular neutrophilic panniculitis, ILD, basal ganglia calcifications, cytopenia | - CAMT: some neurological associations, possibly related to ICH - TAR: skeletal defects (absent radii), cow's milk intolerance, renal tract abnormalities, cardiac defects) - RUNX1: platelet function defect | - Radioulnar stenosis - Clinodactyly - Hearing loss - Cardiac malformations - Renal malformations | - Microcephaly - Developmental delay | - Strokes - Vasculitis - Systemic inflammation - Hypogammaglobulinemia |
| Malignancy risk | - MDS/AML - SCC of skin, head/neck, anogenital | - MDS/AML - SCC skin, head/neck, anogenital - BCC skin | MDS/AML | - MDS/AML - Colon cancer - Osteogenic sarcoma | - MDS/AML - SCC skin, anogenital - BCC skin | MDS/AML | - RUNX1/ETV6/ ANKRD26: MDS/AML or ALL - ALL > ETV6, MDS/AML > RUNX1/ANKRD26 | MDS/AML | MDS | None known |
AD, autosomal dominant; AML, acute myeloid leukemia; AR, autosomal recessive; ASD, atrial septal defect; AVM, arteriovenous malformation; BCC, basal cell carcinoma; CAMT, congenital amegakaryocytic thrombocytopenia; DC, dyskeratosis congenita; HPV, human papilloma virus; ICH, intracranial hemorrhage; ILD, interstitial lung disease; MDS, myelodysplastic syndrome; RP, ribosomal protein; SAAD, SAMD9L-associated autoinflammatory disease; SCC, squamous cell carcinoma; TAR, thrombocytopenia absent radii; VSD, ventricular septal defect; XRL, X-linked recessive. References listed as superscript.