The Emberger syndrome is a rare, autosomal dominant, genetic disorder caused by familial or sporadic inactivating mutations in one of the two parental GATA2 genes. The mutation results in a haploinsufficiency (i.e. reduction) in the levels of the genes product, the GATA2 transcription factor. This transcription factor is critical for the embryonic development, maintenance, and functionality of blood-forming, lympathic-forming, and other tissues. The syndrome includes as its primary symptoms: serious abnormalities of the blood such as the myelodysplastic syndrome and acute myeloid leukemia; lymphedema (i.e. fluid retention and tissue swelling caused by a compromised lymphatic system) of the lower limbs, and sensorineural hearing loss. However, the anomalies caused by GATA2 mutations are highly variable with some individuals showing little or no such symptoms even in old age while others exhibit non-malignant types of hematological anomalies; lymphedema in areas besides the lower limbs, little or no hearing loss; or anomalies in other tissues. The syndrome may present with relatively benign signs and/or symptoms and then progress rapidly or slowly (i.e. over years or decades) to the myelodysplastic syndrome and/or acute myeloid leukemia. Alternatively, it may present with one of the latter two life-threatening disorders.The Emberger syndrome is only one of the manifestations of inactivating GATA2 mutations. Other manifestations include: 1 Monocytopenia and Mycobacterium Avium Complex/Dendritic Cell, Monocyte, B and NK Lymphocyte deficiency (i.e. MonoMAC or MonoMAC/DCML); 2) familial myelodysplastic syndrome/acute myeloid leukemia (i.e.
It may be especially difficult to diagnose the syndrome in the absence of at least one of the latter two clinical signs or in individuals who exhibit anomalies strongly associated with one of the other manifestations of GATA2 deficiency. DNA sequencing of the full GATA2 gene coding region including the intron4 enhancer by Sanger sequencing or high-throughput methods along with DNA copy number analysis should establish the presence of GATA2 gene mutations; comparison of detected gene mutations to the list of inactivating GATA2 gene mutations plus the clinical presentation and family history are essentials in making the diagnosis of the syndrome and its type of presentation. Treatment
Standard measures are use for the treatment of lymphedema, sensorineural hearing loss, and the other non-malignant anomalies associated with the Emberger syndrome. However, treatment of the disorders myelodysplastic syndrome and acute myeloid leukemia differs somewhat from standard measures. Like other GATA2 insufficiencies, Emberger syndrome is associated with a deficiency of hematological stem and early progenitor cells that is often due to a hereditary loss of one GATA2 gene. Consequently, the use of radical myeloablative conditioning regimens to remove native bone marrow stem/progenitor cells in preparation for hematopoietic stem cell transplantation may entail excessive morbidity and mortality. While no controlled studies on the treatment of the hematological disorders of the syndrome have been reported, current recommendations by multiple authorities suggest the use of hematopoietic stem cell transplantation using non-myeloablative conditioning methods be used when indicated.