Deafness-lymphedema-leukemia syndrome

Other Names: Emberger syndrome; Lymphedema, primary, with myelodysplasia

Deafness-lymphedema-leukemia syndrome is a very rare genetic disorder characterized by swelling (lymphedema), a weak immune system (immunodeficiency), and blood disorders.

Cause

It is caused by a mutation in the GATA2 gene.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

It is inherited in an autosomal dominant way.

Signs and symptoms

Signs and symptoms may include congenital deafness, swelling of the legs and genitalia, a type of cancer known as acute myeloblastic leukemia, reduction of the blood cells (pancitopenia), scarring of the liver (cirrhosis), heart problems and cerebellar atrophy (volume loss of the cerebellum which is part of the brain). Patients may also have closely spaced eyes (hypotelorism), skin folds in the inner corner of the eyes, long tapering fingers and/or neck webbing, recurrent infections in the swelled legs, and many warts.

Diagnosis

Examination of circulating blood cells, bone marrow cells, and the GATA2 nucleotide sequence of individuals with Emberger syndrome typically evidences abnormalities which are not distinctively different from those of individuals with other manifestations of GATA2 deficiency.

The specific diagnosis of Emberger syndrome depends on detecting mutations of the GATA2 gene in a setting of clinical findings of hematological disorders, lymphedema, and neurosensory hearing loss. 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 disorder's 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. The use of this procedure should be anticipatory and occur before the development of an excess of progenitor cells populate the bone marrow in cases of myelodyspasia as well as before the development of acute myeloid leukemia. Accordingly, individuals should be routinely monitored by bone marrow examinations and complete blood counts. Furthermore, the relatives of patients afflicted with the syndrome or any of other manifestations of GATA2 deficiency should be tested for GATA2 mutations. Individuals with such mutations are not candidates for donating their stem cells of Emberger syndrome patients. Reversion of the bone marrow to full immune restitution with improved expression of GATA2 can take up to several years after transplantation.

Prognosis

Prognosis of the Emberger syndrome depends heavily on the speed of its progression to bone marrow failure, myelodysplasia with excessive blast cells, or acute myeloid leukemia. Intervention with non-myeloablative hematopoietic stem cell transplantation before development of the latter two disorders is thought to improve survival indefinitely in most cases. While not yet tested, this transplantation intervention would seem to offer a similar benefit in cases of severe, potentially lethal bone marrow failure.

NIH genetic and rare disease info

• NIH info on Deafness-lymphedema-leukemia syndrome

Deafness-lymphedema-leukemia syndrome is a rare disease.

Deafness-lymphedema-leukemia syndrome Resources
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