Classification of congenital thrombocytopenias including gene defect, inheritance, and associated features.
| Inherited Thrombocytopenias . | Abbre- viation . | Gene (Localization) . | Inherited Pattern . | Clinical and Laboratory Features . |
|---|---|---|---|---|
| Wiskott-Aldrich syndrome | WAS | WAS (Xp11) | X-L | Severe immunodeficiency. Defective WAS protein. Small platelets. Eczema. |
| X-linked thrombocytopenia | XLT | WAS (Xp11) Exon2 | X-L | Mild immunodeficiency. Defective WAS protein. Small platelets. |
| Familial platelet disorder with predisposition to acute myelogenous leukemia | FPD/AML | CBFA2 (21q22) | AD | Propensity to develop myelodysplastic syndrome or acute myelogenous leukemia. Normal platelet size. Dysfunctional platelets. |
| Amegakaryocytic thrombocytopenia | CAMT | c-Mpl (1p34) | AR | Hypomegakaryocytic thrombocytopenia evolving into bone marrow aplasia. Normal platelet size. |
| Amegakaryocytic thrombocytopenia with radio-ulnar synostosis | CTRUS | HOXA11 (7p15-14) | AD | Reduced-absent megakaryocytes. Radio-ulnar synostosis ± other malformations. Possible sensorineural hearing loss. Normal platelet size. |
| Thrombocytopenia with absent radii | TAR | n.d. | AR | Thrombocytopenia usually severe in the first year of life. Reduced megakaryocytes. Bilateral radial aplasia ± other malformations. Normal platelet size. |
| Bernard-Soulier syndrome | BSS | GPIbα (17p13) GPIbβ (22q11) GPIX (3q21) | AD | Defective GPIb/IX/V. Homozygous subjects: defective ristocetin- induced platelet agglutination. Giant platelets. Heterozygous subjects: mild thrombocyto- penia, normal ristocetin-induced platelet agglutination. Large platelets. |
| Velocardiofacial syndrome/DiGeorge | VCFS | 1q22, 10 p4 | AD | Right heart defect. Palate defect. T cell immune deficiency. Evans syndrome. Large platelets. |
| Von Willebrand disease type 2B Platelet type von Willebrand disease | VW2B PltVWF | GP1bα (17p13) | AD AD | Platelet clumping. Abnormal (hyperreactive) ristocetin-induced platelet agglutination. |
| Benign Mediterranean macrothrombocytopenia | n.d. | n.d. | AD | Dysmegakaryocytopoiesis. Large platelets. |
| X-linked thrombocytopenia and dyserythropoiesis with or without anemia X-linked thrombocytopenia- thalassemia | XLTT | GATA-1 (Xp11) | X-L | Anemia (mild to nil), unbalanced globin chain synthesis resembling β-thalassemia, peripheral red cell hemolysis, dysmegakaryocytopoiesis, splenomegaly. Large platelets. |
| MYH9-related disease | ||||
| May-Hegglin anomaly | MHA | MYH9 (22q12-13) | AD | Neutrophil inclusions ± hearing loss, cataract and/or renal defect. Giant platelets. |
| Sebastian syndrome | SBS | MYH9 (22q12-13) | AD | Neutrophil inclusions ± hearing loss ± cataract ± renal defect. Giant platelets. |
| Fechtner syndrome | FTNS | MYH9 (22q12-13) | AD | Neutrophil inclusions ± hearing loss ± cataract ± renal defect. Giant platelets. |
| Epstein syndrome | EPTS | MYH9 (22q12-13) | AD | Neutrophil inclusions ± hearing loss ± cataract ± renal defect. Giant platelets. |
| Gray platelet syndrome | GPS | n.d. | AD | Pale platelets on blood films due to reduced- absent α-granules. Large platelets. |
| Inherited Thrombocytopenias . | Abbre- viation . | Gene (Localization) . | Inherited Pattern . | Clinical and Laboratory Features . |
|---|---|---|---|---|
| Wiskott-Aldrich syndrome | WAS | WAS (Xp11) | X-L | Severe immunodeficiency. Defective WAS protein. Small platelets. Eczema. |
| X-linked thrombocytopenia | XLT | WAS (Xp11) Exon2 | X-L | Mild immunodeficiency. Defective WAS protein. Small platelets. |
| Familial platelet disorder with predisposition to acute myelogenous leukemia | FPD/AML | CBFA2 (21q22) | AD | Propensity to develop myelodysplastic syndrome or acute myelogenous leukemia. Normal platelet size. Dysfunctional platelets. |
| Amegakaryocytic thrombocytopenia | CAMT | c-Mpl (1p34) | AR | Hypomegakaryocytic thrombocytopenia evolving into bone marrow aplasia. Normal platelet size. |
| Amegakaryocytic thrombocytopenia with radio-ulnar synostosis | CTRUS | HOXA11 (7p15-14) | AD | Reduced-absent megakaryocytes. Radio-ulnar synostosis ± other malformations. Possible sensorineural hearing loss. Normal platelet size. |
| Thrombocytopenia with absent radii | TAR | n.d. | AR | Thrombocytopenia usually severe in the first year of life. Reduced megakaryocytes. Bilateral radial aplasia ± other malformations. Normal platelet size. |
| Bernard-Soulier syndrome | BSS | GPIbα (17p13) GPIbβ (22q11) GPIX (3q21) | AD | Defective GPIb/IX/V. Homozygous subjects: defective ristocetin- induced platelet agglutination. Giant platelets. Heterozygous subjects: mild thrombocyto- penia, normal ristocetin-induced platelet agglutination. Large platelets. |
| Velocardiofacial syndrome/DiGeorge | VCFS | 1q22, 10 p4 | AD | Right heart defect. Palate defect. T cell immune deficiency. Evans syndrome. Large platelets. |
| Von Willebrand disease type 2B Platelet type von Willebrand disease | VW2B PltVWF | GP1bα (17p13) | AD AD | Platelet clumping. Abnormal (hyperreactive) ristocetin-induced platelet agglutination. |
| Benign Mediterranean macrothrombocytopenia | n.d. | n.d. | AD | Dysmegakaryocytopoiesis. Large platelets. |
| X-linked thrombocytopenia and dyserythropoiesis with or without anemia X-linked thrombocytopenia- thalassemia | XLTT | GATA-1 (Xp11) | X-L | Anemia (mild to nil), unbalanced globin chain synthesis resembling β-thalassemia, peripheral red cell hemolysis, dysmegakaryocytopoiesis, splenomegaly. Large platelets. |
| MYH9-related disease | ||||
| May-Hegglin anomaly | MHA | MYH9 (22q12-13) | AD | Neutrophil inclusions ± hearing loss, cataract and/or renal defect. Giant platelets. |
| Sebastian syndrome | SBS | MYH9 (22q12-13) | AD | Neutrophil inclusions ± hearing loss ± cataract ± renal defect. Giant platelets. |
| Fechtner syndrome | FTNS | MYH9 (22q12-13) | AD | Neutrophil inclusions ± hearing loss ± cataract ± renal defect. Giant platelets. |
| Epstein syndrome | EPTS | MYH9 (22q12-13) | AD | Neutrophil inclusions ± hearing loss ± cataract ± renal defect. Giant platelets. |
| Gray platelet syndrome | GPS | n.d. | AD | Pale platelets on blood films due to reduced- absent α-granules. Large platelets. |