GATA2 deficiency is a rare autosomal dominant condition due to haploinsufficiency of the GATA2 gene that typically presents later in life (median age of 20 at initial presentation). The GATA2 gene encodes a zinc finger transcription factor that serves a critical role in hematopoietic regulation as well as vascular and lymphatic development. Mutation is characterized by profoundly decreased or absent monocytes, dendritic cells, natural killer cells, and B cells.

The GATA2 mutation has been found to underlie at least 5 previously described conditions that are now recognized as phenotypic variants of the same genetic disorder. Specifically, these include monocytopenia and Mycobacterium avium complex infection (MonoMAC) syndrome; dendritic cell, monocyte, B and NK lymphoid deficiency; familial myelodysplastic syndrome / acute myeloid leukemia; Emberger syndrome (primary lymphedema with myelodysplasia); and classical NK-cell deficiency. As these names suggest, GATA2 deficiency causes a primary immunodeficiency associated with disseminated opportunistic infections and lymphoproliferative disorders.

Affected patients are at increased risk for multiple infections including nontuberculous mycobacteria, disseminated opportunistic and invasive fungi, and severe / recalcitrant herpesvirus and papillomavirus disease. Over half of all patients will develop myelodysplastic syndrome, with a smaller proportion going on to develop acute myeloid leukemia or chronic myelomonocytic leukemia. Multiple cutaneous malignancies have also been described, typically those associated with a viral pathogenesis such as human papillomavirus-associated squamous cell carcinoma, Merkel cell carcinoma (Merkel cell polyomavirus), and Epstein-Barr virus-positive smooth muscle tumors.