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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A GATA2 Mutation is Suspected in the Following Patients:

  • Patients who develop MDS or AML at a young age

  • People with MDS/AML who have a positive family history of MDS or AML

  • Patients with MDS/AML as well as monosomy 7 / trisomy 8.

  • Patients with MDS/AML who also exhibit a lymphedema or hearing loss.

  • Patients with MDS/AML who also exhibit signs of dysmorphia.

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

  • HLA typing for a potential stem cell transplant

  • After leukemia is diagnosed, extensive diagnostics according to the respective study protocol

Differential Diagnoses

  • MDS/AML with other underlying mutations

  • Other congenital diseases with bone marrow failure

  • Immunodeficiencies due to other causes

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

  • Approximately 70% of mutation carriers develop MDS or AML.

  • Patients with MDS have a high risk of developing AML or chronic myelomonocytic leukemia (CMML).

  • The average age at diagnosis for hematological neoplasia is 20 years, with an age range of 12 to 35 years.

  • The first hematological sign may be single-cell cytopenia – or pancytopenia. Monocytosis often occurs as well.

  • Hypocellular bone marrow, dysplastic megakaryocytes, and increased reticulin fibrosis are frequently exhibited.

Immunological Manifestations

  • Monocytopenia, B-cell lymphocytopenia, NK (natural killer) cell deficiency

  • Infections, particularly with human papillomavirus (HPV) and mycobacteria, especially Mycobacterium avium complex

Other Clinical and Genetic Anomalies

  • Lymphedema (affecting the extremities or as a hydrocele testis)

  • Sensorineural hearing loss

  • Behavioral disorders, autism, ADHD

  • Hypothyroidism, urogenital malformations, unilateral/bilateral ptosis, fetal hydrops

  • Signs of dysmorphia: hypotelorism, epicanthal folds, long and tapered fingers, pterygium colli

  • Genetic: monosomy 7, trisomy 8, acquired ASXL1 mutation

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

  • Clinical examination

  • Complete blood count

  • Bone marrow puncture

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.