This web page was produced as an assignment for Genetics 564, an undergraduate course at UW-Madison.
What is Emberger Syndrome?
Emberger Syndrome is a rare autosomal dominant disorder with incomplete penetrance that is caused by mutations in the GATA2 gene. It is characterized by the co-occurrence of primary lymphedema with a predisposition to acute myeloid leukemia (AML) [1]. In primary lymphedema, a hereditary condition causes lymphatic vessels to be either missing or impaired. This results in a buildup of lymphatic fluid, which leads to swelling [2]. AML is a cancer of the blood and bone marrow in which there is an accumulation of abnormal white blood cells (myeloblasts) that restricts the production of normal blood cells.
This disease has additional symptoms that may vary with each case. Some of the most common features include severe and widespread cutaneous warts, sensorineural deafness, and minor anomalies (mild hypotelorism, neck webbing, and slender fingers) [1, 3]. While the onset of Emberger Syndrome is normally during childhood, there have been some cases that do not arise until adulthood [3]. |
Figure 1: One of the common symptoms of Emberger Syndrome is the presence of cutaneous warts.
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Genetic Basis
Emberger Syndrome is caused by GATA2 haploinsufficiency. GATA2 is a human gene that encodes the protein GATA2, which plays an essential role in regulating the transcription of genes involved in the development and proliferation of hematopoietic and endocrine cell lineages [4]. The figure below shows the eight observed independent mutations in the GATA2 gene that have been found in patients with Emberger Syndrome. Each variant is believed to have substantial impact upon the function of the gene [3].
Additionally, variations near GATA2 were found to be related to the ability to differentiate similar pitches and durations of sound as well as recognize musical pattern [5]. This is interesting because many people with Emberger Syndrome develop sensorineural deafness.
The GATA2 gene is located on the long arm of chromosome 3 at position 21.3 [6].
Diagnosis & Treatment
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The first step in diagnosing Emberger Syndrome is observing signs of primary lymphedema. There are numerous diagnostic tests for lymphedema, such as soft tissue imaging, history and physical examination, lymph vessel & lymph node imaging, and genetic testing [7]. Children displaying signs of primary lymphedema should be screened for hematological abnormalities. Diagnostic tests for AML include: complete blood count & peripheral blood smear, bone marrow aspiration & biopsy, cytogenetic analysis, and molecular analysis [8]. The presence of both primary lymphedema and AML (or predisposition to AML) lead to a diagnosis of Emberger Syndrome. While there is no cure for this disease, there are multiple treatments that patients can go through to try and improve their health. These treatments must address both lymphedema and AML. Since primary lymphedema is progressive, early diagnosis leads to more effective treatment. |
The main treatment used is Complete Decongestive therapy (CDT), which decreases swelling and increases lymph drainage from the congested areas [7]. In addition to CDT, patients must undergo treatment to address the AML. The most common form of treatment consists of two chemotherapy phases: induction and consolidation. Induction destroys most of the leukemia cells and, if it is considered successful, is followed by the consolidation phase which attempts to destroy any remaining leukemia cells and prevent a relapse [9].
References:
1) Mansour, Sahar et al. (2010). Emberger Syndrome – Primary Lymphedema With Myelodysplasia: Report of Seven New Cases.American Journal of Medical Genetics, Part A: 2287-2296.
2) National Lymphedema Network: http://www.lymphnet.org/le-faqs/what-is-lymphedema
3) Ostergaard, Pia et al. (2011). Mutations in GATA2 cause primary lymphedema associated with a predisposition to acute myeloid leukemia (Emberger Syndrome). Nature Genetics, 43(10): 929-930.
4) Gene Cards: The Human Gene Compendium: http://www.genecards.org/cgi-bin/carddisp.pl?gene=GATA2
5) Oikkonen, J et al. (2015). A genome-wide linkage and association study of musical aptitude identifies loci containing genes related to inner ear development and neurocognitive functions. Molecular Psychiatry, 20: 275-282.
6) Genetics Home Reference: http://ghr.nlm.nih.gov/gene/GATA2
7) NLN Medical Advisory Committee (2011). The Diagnosis and Treatment of Lymphedema. National Lymphedema Network.
8) Seattle Cancer Care Alliance – Acute Myeloid Leukemia (AML): http://www.seattlecca.org/diseases/adult-acute-myeloid-leukemia-symptoms-diagnosis.cfm
9) American Cancer Society – Leukemia, Acute Myeloid: http://www.cancer.org/cancer/leukemia-acutemyeloidaml/detailedguide/leukemia-acute-myeloid-myelogenous-treating-typical-treatment-of-aml
Images: (in order of appearance)
Figure 1: https://www.aad.org/dermatology-a-to-z/diseases-and-treatments/u---w/warts
Figure 2: http://www.nature.com/ng/journal/v43/n10/abs/ng.923.html
Figure 3: http://www.genecards.org/cgi-bin/carddisp.pl?gene=GATA2
Figure 4: http://www.lymphedemablog.com
1) Mansour, Sahar et al. (2010). Emberger Syndrome – Primary Lymphedema With Myelodysplasia: Report of Seven New Cases.American Journal of Medical Genetics, Part A: 2287-2296.
2) National Lymphedema Network: http://www.lymphnet.org/le-faqs/what-is-lymphedema
3) Ostergaard, Pia et al. (2011). Mutations in GATA2 cause primary lymphedema associated with a predisposition to acute myeloid leukemia (Emberger Syndrome). Nature Genetics, 43(10): 929-930.
4) Gene Cards: The Human Gene Compendium: http://www.genecards.org/cgi-bin/carddisp.pl?gene=GATA2
5) Oikkonen, J et al. (2015). A genome-wide linkage and association study of musical aptitude identifies loci containing genes related to inner ear development and neurocognitive functions. Molecular Psychiatry, 20: 275-282.
6) Genetics Home Reference: http://ghr.nlm.nih.gov/gene/GATA2
7) NLN Medical Advisory Committee (2011). The Diagnosis and Treatment of Lymphedema. National Lymphedema Network.
8) Seattle Cancer Care Alliance – Acute Myeloid Leukemia (AML): http://www.seattlecca.org/diseases/adult-acute-myeloid-leukemia-symptoms-diagnosis.cfm
9) American Cancer Society – Leukemia, Acute Myeloid: http://www.cancer.org/cancer/leukemia-acutemyeloidaml/detailedguide/leukemia-acute-myeloid-myelogenous-treating-typical-treatment-of-aml
Images: (in order of appearance)
Figure 1: https://www.aad.org/dermatology-a-to-z/diseases-and-treatments/u---w/warts
Figure 2: http://www.nature.com/ng/journal/v43/n10/abs/ng.923.html
Figure 3: http://www.genecards.org/cgi-bin/carddisp.pl?gene=GATA2
Figure 4: http://www.lymphedemablog.com
Nikita Tongas
[email protected]
15 May 2015
<www.genetics564.weebly.com>
[email protected]
15 May 2015
<www.genetics564.weebly.com>