Definition
GATA2 deficiency encompasses multiple diseases caused by mutations in the GATA2 gene: immunodeficiency 21 (MonoMAC, OMIM #614172), Emberger syndrome (OMIM #614038), a predisposition to myelodysplastic syndrome (MDS; OMIM #614286), and a predisposition to acute myeloid leukemia (AML; OMIM #601626).
Key Data
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Synonyms | Emberger syndrome (MDS, lymphedema, and hearing loss) MonoMAC syndrome (immunodeficiency 21) |
Gene | GATA2 |
Gene product | GATA2 |
Function | Transcription factor that regulates gene expression in hematopoietic cells. It contains two zinc finger (ZF) domains that mediate DNA binding and protein interactions. |
Heredity | Autosomal dominant |
Prevalence | 7% of cases of primary MDS in children are based on a GATA2 mutation. 72% of adults with MDS and monosomy 7 have a GATA2 mutation (usually de novo). |
Genotype-phenotype correlation | The most frequent mutations are truncating mutations before ZF2, missense mutations within ZF2, and non-coding variants in the +9.5kb regulatory region of GATA2. All previously described germline mutations predispose to MDS/AML, infectious diseases, and cytopenia, but only complete haploinsufficiency or GATA2 loss-of-function mutations predispose to lymphedemas. |
Penetrance | Approximately 90% up to the age of 60 for both hematological and immunological diseases Myeloid neoplasia occurs in approximately 70% of mutation carriers. |
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Diagnosis
A GATA2 Mutation is Suspected in the Following Patients:
Genetic Diagnostics
The diagnosis of “GATA2 deficiency” is confirmed by the detection of a germline mutation in the GATA2 gene through single-gene analysis or panel studies consisting of multiple genes.
Additional Clinical Diagnostics after the Diagnosis Has Been Made
Differential Diagnoses
Clinical Presentation
The pattern of clinical symptoms is very heterogeneous. The primary manifestations are cytopenia and myeloid neoplasia. However, it is also possible for MDS with excessive blasts to develop without prior symptoms or other signs and in the absence of a concomitant family history. In addition, there may be immunodeficiencies, sometimes with severe bacterial and viral infections, along with lymphedemas and hearing loss. A combination of non-hematological manifestations without the presence of MDS or AML may occur as part of a GATA2 mutation as well.
Hematological Manifestations
Immunological Manifestations
Other Clinical and Genetic Anomalies
Therapeutic Considerations
Due to the heterogeneous clinical presentation, patients with a GATA2 mutation should be treated by a multidisciplinary team.
Chemotherapy administered for AML should be avoided when there is a GATA2 mutation due to the underlying immunodeficiency and stem cell defect. For this reason, it may be worth considering early stem cell transplants for high-risk patients. The hypocellular bone marrow phase has proven to be the most favorable window of time, since it tends to precede the occurrence of severe complications such as systemic infections or MDS with excess blasts.
Since there is a predisposition to HPV infections, an HPV vaccination may be worth considering.
Surveillance Recommendations
Surveillance Recommendations
At Least Annually
Additional Information
Open Clinical Trials / Registries
Support Groups
Unfortunately, we are as yet unaware of any existing support groups for patients with GATA2 deficiency. We will add new information as it becomes available.