| Subtype | Key causal gene(s) | Inheritance | Hallmark bone marrow morphology | Key clinical features / complications | Key management notes |
|---|---|---|---|---|---|
| **CDA (group)**; MONDO: **MONDO_0019403** | Major associated genes include **CDAN1, CDIN1, SEC23B, KIF23, RACGAP1, GATA1, KLF1** (OpenTargets disease–target associations) (pqac-00000000) | Heterogeneous; includes autosomal recessive and X-linked/TF-related forms depending on subtype (pqac-00000000, pqac-00000004) | Bone marrow usually shows **erythroid hyperplasia** with subtype-specific dyserythropoiesis (pqac-00000005) | Inherited anemias with **ineffective erythropoiesis**; iron overload can occur even without heavy transfusion burden due to **erythroferrone-mediated hepcidin suppression**; differential diagnosis overlaps with hereditary hemolytic anemias and acquired dyserythropoiesis (pqac-00000002, pqac-00000004, pqac-00000005) | Monitoring includes CBC and iron parameters; severe anemia may require transfusion; iron overload should be treated/monitored carefully, especially before HSCT (pqac-00000002, pqac-00000016) |
| **CDA I** | **CDAN1**, **CDIN1/C15orf41** (pqac-00000000) | **Autosomal recessive** (pqac-00000006) | **Internuclear chromatin bridges**; EM shows **“Swiss cheese” / spongy heterochromatin** (pqac-00000005, pqac-00000006) | Moderate to severe anemia; hepatosplenomegaly; macrocytosis; hyperbilirubinemia; gallstones; iron overload/hemosiderosis may develop even in non-transfused patients (pqac-00000006) | Mainly supportive care; RBC transfusions as needed; **interferon therapy** can reduce transfusion dependence; cholecystectomy for symptomatic gallstones; phlebotomy or chelation for iron overload; prenatal/preimplantation testing possible once familial variants are known (pqac-00000002, pqac-00000006) |
| **CDA II** (most common major type) | **SEC23B** (biallelic pathogenic variants) (pqac-00000001, pqac-00000000) | **Autosomal recessive** (pqac-00000001) | **Binucleate erythroid precursors / erythroblasts with two or more nuclei** (pqac-00000005) | Mild to severe normocytic anemia, hemolysis, jaundice, splenomegaly, gallstones, liver iron overload; inadequate reticulocytosis despite anemia; ineffective erythropoiesis with **ERFE overexpression → hepcidin suppression → increased iron absorption** (pqac-00000001, pqac-00000002) | Diagnostic workup: CBC/reticulocytes, bilirubin/haptoglobin, iron studies, MRI for organ iron, bone marrow exam, and genetic testing/NGS; management may include transfusions, iron chelation, splenectomy in selected cases, and HSCT for very severe disease (pqac-00000001, pqac-00000002, pqac-00000016) |
| **CDA II: example SEC23B variants** | Examples reported in recent cohort: **c.1334C>G (p.Thr445Arg), c.1736A>G (p.Tyr579Cys), c.2102G>A (p.Arg701His), c.2074_2077dupGATG (p.Asp693GlyfsTer2), c.1512-2A>G, c.1512-3delinsTT with c.1512-16_1512-7delACTCTGGAAT, c.325G>A (p.Glu109Lys), c.40C>T (p.Arg14Trp)** (pqac-00000008, pqac-00000009, pqac-00000011, pqac-00000014, pqac-00000015) | Autosomal recessive; variants often occur as homozygous or compound heterozygous alleles (pqac-00000008, pqac-00000015) | Same CDA II morphology; some patients also had abnormal membrane protein electrophoresis / band 3 and EM membrane abnormalities in reported series (pqac-00000011) | Reported cohorts showed chronic Coombs-negative hemolytic anemia, hepatosplenomegaly, cholelithiasis, iron overload, and transfusion history in some patients (pqac-00000011, pqac-00000015) | Functional studies showed **reduced SEC23B protein**, limited SEC23A compensation in LCLs, and exon 13–14 skipping for complex intronic alleles; findings support loss-of-function disease mechanism (pqac-00000009, pqac-00000010, pqac-00000014) |
| **CDA III** | **KIF23**, **RACGAP1** (pqac-00000000) | Not specified in gathered evidence for all forms; genetically distinct subtype (pqac-00000000, pqac-00000004) | **Giant multinucleated erythroblasts** (pqac-00000005) | Rare major subtype within CDA classification; specific phenotype details not fully captured in gathered excerpts (pqac-00000004, pqac-00000005) | Supportive care and iron monitoring principles from CDA group apply; subtype-specific evidence in gathered set is limited (pqac-00000002, pqac-00000005) |
| **CDA IV / transcription factor–related and variant forms** | **KLF1**, **GATA1**; broader CDA-associated list in OpenTargets also includes **LPIN2** and other rare associations (pqac-00000000) | **X-linked or other subtype-specific inheritance** may apply for TF-related cytopenias; not fully resolved in gathered excerpts (pqac-00000000, pqac-00000005) | **Multinucleate erythroblasts** reported for CDA IV; GATA1-related disorders may present as dyserythropoietic anemia with thrombocytopenia rather than classic isolated CDA (pqac-00000005) | Includes **GATA1-related cytopenias** and **KLF1-related CDA IV** within modern classification; clinical manifestations are heterogeneous and may extend beyond isolated anemia (pqac-00000004, pqac-00000005, pqac-00000000) | No subtype-specific standard therapy detailed in gathered excerpts; diagnosis relies increasingly on molecular testing/NGS and expert hematopathology review (pqac-00000004, pqac-00000005) |


*Table: This table summarizes major congenital dyserythropoietic anemia subtypes and selected additional/transcription-factor-related forms using only the gathered evidence. It highlights the causal genes, inheritance, hallmark marrow morphology, major clinical features, and practical management points most relevant for a disease knowledge base.*