Table 2. Inherited bone marrow failure syndromes.^{1-3,34,35,41-43,47,50,55,59-61,63,78,91-93}.

Syndrome	Fanconi anemia	Dyskeratosis congenita	Diamond-Blackfan anemia	Shwachman-Diamond syndrome
Pathogenesis	Interstrand crosslink DNA repair	Telomere maintenance	Ribosomal biogenesis	Ribosomal biogenesis
Inheritance: Known genes	AR: FANCA, C, D1, D2, E, F, G, I, J, L, N, O, P, Q, S, T XLR: FANCB	XLR; DKC1 AD; TERT, TERC, TINF2, RTEL1 AR; TERT, WRAP53, NOP10, CTC1, NHP2, USB1, RTEL1	AD: RPS19, RPS17, RPS24, RPL35A, RPL5, RPL11, RPS7, RPS26, RPS10 XLR: GATA1	AR: SBDS
Incidence	1-3/500,000	1/1,000,000	12/1,000,000	1/76,000
Age at the diagnosis, median (range)	6.5 years (birth to 49 years)	14 years (birth to 75 years)	3 months (birth to 64 years)	2 weeks (birth to 11years)
Non-hematological findings	- Short stature - Skin lesions such as café au lait spots or hypo- and hyper-pigmentation - Abnormalities of upper limbs	- Skin lacy reticular pigmentation - Nail dystrophy - Oral leukoplakia - Pulmonary fibrosis	- Craniofacial anomalies, hypertelorism, cleft lip/palate - Low birth weight - Thumb anomalies - Renal and cardiac anomalies	- Exocrine pancreatic dysfunction - Short stature - Metaphyseal dystosis - Thoracic abnormalities - Delayed development
Diagnostic test	- Chromosomal breakage studies - Gene sequencing	- Telomere length measurement - Gene sequencing	- Fetal hemoglobin and erythrocyte adenosine deaminase activity - Gene sequencing	- Serum trypsinogen and isoamylase - Gene sequencing
Cytogenetic abnormalities	1q+, 3q+, 21q /RUNX1 (cryptic RUNX1 rearrangement), -7/7q, 11q-	Monosomy 7a, Monosomy 10	N/A	i(7q), del(20q)
Hematological presentations	Pancytopenia with macrocytosis	Cytopenia, often associated with thrombocytopenia	- Macrocytic anemia with no other significant cytopenia - Reticulocytopenia	- Neutropenia, sometimes anemia and thrombocytopenia
Hematological malignancy	MDS, AML	MDS, AML	MDS, AML, ALL	MDS, AML
Cumulative incidence of bone marrow failure	90% by 40 years of age	Around 45% by 40 years of age	>50% by 70 years of age	40% by 50 years of age
Cumulative incidence of MDS/Leukemia	MDS: 50% by 50 years of age Leukemia: up to 5% by 30 years of age	MDS: 20% by 50 years of age Leukemia: up to 10% by 70 years of age	MDS: 5% by 50 years of age AML: 5% by 46 years of age	MDS: 65% by 50 years of age AML: 5% by 20 years of age
Other malignancy	- Head and neck SCC - Liver tumors - Vaginal SCC - Brain tumors	- Head and neck SCC - Gastrointestinal and anogenital tumors	- Osteosarcoma - Colon cancer - Lung cancer - Cervical cancer	Limited cases
Survival, median	29 years	49 years	67 years	41 years
Bone marrow histopathology	- Hypocellularity for age, or variable cellularity, depending on the stage of the disease - Dyserythropoiesis in more than 90% of patients - Fanconi anemia is found in 14.5% of patients with histomorphological findings consistent with hypo- or normocellular RCC. - Fanconi anemia-related MDS is highly associated with increased blasts and dysgranulopoiesis.	- Hypocellularity for age, or variable cellularity, depending on the stage of the disease - Some degree of dysplasia in any lineage is often present. - Dyskeratosis congenita is found in 1.6%-2.5% of patients with histomorphological findings consistent with hypo- or normocellular RCC.	- Normal marrow cellularity with a paucity of erythroid precursors - Erythroid precursors are absent or sparsely distributed and/or in a few small clusters lacking maturing/matured erythroid cells. - Normal granulopoiesis and megakaryopoiesis - Frequent lymphocytosis	- Hypocellularity for age, or variable cellularity, depending on the stage of the disease - Myeloid hypoplasia, often with left-shifted maturation. - Mild dyshematopoiesis in any lineage is commonly present.

AD, autosomal dominant; ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; AR, autosomal recessive; MDS, myelodysplastic syndrome; N/A, not available; RCC, refractory cytopenia of childhood; SCC, squamous cell carcinoma; XLR, X-linked recessive

a. Secondary MDS