Differential Diagnosis
GATA1-related cytopenia must be distinguished from other acquired and hereditary thrombocytopenias (e.g., Wiskott-Aldrich syndrome, which is also X-linked), platelet function abnormalities, and anemias . Algorithms exist to help differentiate among these disorders . However, the clinical phenotypes of GATA1-related cytopenias vary greatly and overlap considerably with other genetic causes of cytopenia. Hence, a genetic diagnosis is almost always required for confirmation. A multigene panel is often used to establish the diagnosis of a hereditary thrombocytopenia and thereby facilitate appropriate surveillance (some types of hereditary thrombocytopenia are associated with increased malignancy risk) and genetic counseling. Of note: • Numerous congenital thrombocytopenias may be considered in the differential diagnosis . In GATA1-related thrombocytopenia, platelets are usually large and may be hypogranular. There may be associated platelet aggregation defects and/or a prolonged bleeding time. Relatively common congenital causes of macrothrombocytopenia that could be confused with GATA1-related disorders are described in . • Thrombocytopenia may be the initial manifestation of bone marrow failure in individuals with a telomere biology disorder (e.g., dyskeratosis congenita). • Cryptorchidism and/or hypospadias may suggest the involvement of GATA1 but are not always present. • Congenital causes of anemia that could potentially be confused with GATA1-related disorders are described in . Table 3. Selected Genes of Interest in the Differential Diagnosis of GATA1-Related Cytopenia
Gene | Disorder | MOI | Clinical Characteristics |
|---|
ETV6 thrombocytopenia predisposition to leukemia | AD | Mild-to-moderate thrombocytopenia w/platelet function defects; risk of hematologic malignancy RUNX1 | — |
RUNX1 familial platelet disorder w/assoc myeloid malignancies | AD | Mild-to-moderate thrombocytopenia w/platelet function defects; risk of hematologic malignancy | — |
WAS | Wiskott-Aldrich syndrome (See WAS-Related Disorders.) | XL | Small platelets, eczema (~80%), immunodeficiency; persons may have isolated microthrombocytopenia. Congenital macrothrombocytopenia GP1BA GP1BB |
GP9 | Bernard-Soulier syndrome (BSS) (OMIM 231200) | AR | Severe bleeding disorder w/severely defective ristocetin-induced platelet agglutination; heterozygotes may have mild disease. GP1BA |
GP1BB | Mediterranean thrombocytopenia (OMIM 153670) | AD | Phenotype typically milder than BSS; dysmegakaryo-cytopoiesis2 MYH9 |
MYH9-related disease | AD | Platelet macrocytosis, thrombocytopenia, neutrophil inclusions; most persons have extrahematologic manifestation(s) (e.g., hearing loss, cataract, renal defects). | — |
NBEAL22 | Gray platelet syndrome (OMIM 139090) | AR3 | Pale platelets /or absent alpha granules. Anemia BRCA1 BRCA2 BRIP1 ERCC4 FA... |
Source: GeneReviews — "GATA1-Related Cytopenia"
