Features of select inherited bone marrow failure and inherited MDS/leukemia predisposition syndromes that may present as aplastic anemia
| Syndrome . | Congenital findings . | Malignancy risk . | Screening test . | Genetics . | Other hints . |
|---|---|---|---|---|---|
| Fanconi anemia | Ear abnormalities, heart defects, short stature, skin pigmentation (café-au-lait spots or hypopigmentation), skeletal anomalies (thumbs, arms), TE fistula, triangular facies, urogenital defects | AML, MDS, GYN CA, head and neck CA, and others | Increased chromosome breakage | FANCA, C, G account for 95% of cases | Sensitivity to chemotherapy |
| GATA2 deficiency | Lymphedema, immunodeficiency with atypical mycobacterial infections | AML, MDS | GATA2 | Megakaryocyte atypia, pediatric MDS with monosomy 7, del7q, trisomy 8, der(1;7) | |
| SAMD9/SAMD9L disorders | MIRAGE (SAMD9): MDS, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy Ataxia-pancytopenia syndrome (SAMD9L): cerebellar atrophy and white matter hyperintensities, gait disturbance, nystagmus | AML, MDS | SAMD9, SAMD9L | Pediatric MDS with monosomy 7, del7q, or CN-LOH 7q | |
| Short telomere syndromes | Young adults: infections, nail dystrophy, oral leukoplakia, skin hyperpigmentation Adults: emphysema, early hair graying, immune deficiency, liver fibrosis/cirrhosis, macrocytosis, pulmonary AVMs and HPS | AML, MDS Rectal adenocarcinoma, SCC anus/oral cavity/tongue | Short telomere lengths (correlates with phenotype) | DKC1, RTEL1, TERT, TERC, TINF2, RTEL1 account for majority of cases | |
| Shwachman-Diamond Syndrome | Pancreatic insufficiency (can improve with age), skeletal abnormalities | AML, MDS | Low pancreatic isoamylase (>3 years old) and low fecal elastase (pediatric and adult patients) | SBDS, SRP54, ELF1, DNAJC21 | Isolated neutropenia, somatic mutations in EIF6 and TP53 |
| Syndrome . | Congenital findings . | Malignancy risk . | Screening test . | Genetics . | Other hints . |
|---|---|---|---|---|---|
| Fanconi anemia | Ear abnormalities, heart defects, short stature, skin pigmentation (café-au-lait spots or hypopigmentation), skeletal anomalies (thumbs, arms), TE fistula, triangular facies, urogenital defects | AML, MDS, GYN CA, head and neck CA, and others | Increased chromosome breakage | FANCA, C, G account for 95% of cases | Sensitivity to chemotherapy |
| GATA2 deficiency | Lymphedema, immunodeficiency with atypical mycobacterial infections | AML, MDS | GATA2 | Megakaryocyte atypia, pediatric MDS with monosomy 7, del7q, trisomy 8, der(1;7) | |
| SAMD9/SAMD9L disorders | MIRAGE (SAMD9): MDS, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy Ataxia-pancytopenia syndrome (SAMD9L): cerebellar atrophy and white matter hyperintensities, gait disturbance, nystagmus | AML, MDS | SAMD9, SAMD9L | Pediatric MDS with monosomy 7, del7q, or CN-LOH 7q | |
| Short telomere syndromes | Young adults: infections, nail dystrophy, oral leukoplakia, skin hyperpigmentation Adults: emphysema, early hair graying, immune deficiency, liver fibrosis/cirrhosis, macrocytosis, pulmonary AVMs and HPS | AML, MDS Rectal adenocarcinoma, SCC anus/oral cavity/tongue | Short telomere lengths (correlates with phenotype) | DKC1, RTEL1, TERT, TERC, TINF2, RTEL1 account for majority of cases | |
| Shwachman-Diamond Syndrome | Pancreatic insufficiency (can improve with age), skeletal abnormalities | AML, MDS | Low pancreatic isoamylase (>3 years old) and low fecal elastase (pediatric and adult patients) | SBDS, SRP54, ELF1, DNAJC21 | Isolated neutropenia, somatic mutations in EIF6 and TP53 |
AML, acute myeloid leukemia; AVM, arteriovenous malformations; CA, cancer; GYN CA, gynecological cancers; HPS, hepatopulmonary syndrome; SCC, squamous cell carcinoma; TE, tracheoesophageal fistula.