What is ETV6 deficiency?

ETV6 deficiency, or thrombocytopenia 5, is a genetic disease caused by mutations – or genetic changes – in the ETV6 gene. Characteristic features include a reduction in the number of blood platelets (thrombocytopenia) with or without a tendency to bleed, enlarged red blood cells (macrocytosis), and an increased risk of developing acute leukemia (mainly B-ALL), myelodysplastic syndrome (MDS, a disease of the bone marrow), or – more rarely – other tumors.

How is ETV6 deficiency diagnosed?

Suspected Diagnosis

An ETV6 mutation should be suspected and genetically tested for whenever there is a pronounced familial incidence of mild to moderate thrombocytopenia or whenever there is a combination of thrombocytopenia and leukemia or a solid tumor.

Genetic Diagnostics

The diagnosis of “ETV6 deficiency” is confirmed by the detection of a mutation – or genetic change – in the ETV6 gene.

What is the risk of cancer?

Around 25% of patients with an ETV6 mutation develop an acute leukemia or MDS. The most frequent malignant disease of the blood formation system (hematological malignancy) is pre-B-ALL (acute lymphoid leukemia of the B-cell lineage), with a currently observed average age of incidence of 7 years (age range of 2-37 years). However, other hematological malignancies have been described as well, such as MDS, AML (acute myeloid leukemia), and chronic myelomonocytic leukemia (CMML).

In addition to diseases of the blood formation system, an ETV6 mutation is also associated with the occurrence of other malignant tumors. Early-onset colon cancer has been reported in a few patients, and a few cases of breast cancer, meningioma (a brain tumor), small intestinal cancer, and kidney cancer.

In addition to the increased risk of cancer, it is also common for mild to moderate thrombocytopenia to occur. There is not necessarily always a tendency to bleed, usually it is associated with mild to moderate bleeding episodes, and only rarely with a pronounced tendency to bleed. Typical symptoms include nose and/or gum bleeds, increased bruising, and prolonged menstrual periods. Thrombocytopenia and a tendency to bleed can already manifest during infancy.

What causes ETV6 deficiency?

ETV6 deficiency is caused by a mutation – or genetic change – in the ETV6 gene. This gene encodes the ETV6 transcription factor, which plays an important role in the development of blood cells. Now if the ETV6 gene is altered, the transcription factor can no longer function correctly, resulting in the development of leukemia.

The ETV6 deficiency can be passed on by parents to their children. In these cases, it is inherited as an autosomal dominant disease.

Is there a treatment?

Mild to moderate thrombocytopenia without a tendency to bleed generally does not require any treatment. During childbirth or major surgery, the appropriate blood products should be available and administered if there is heavy bleeding.

Treatment of MDS or leukemia in patients with an ETV6 mutation should be discussed thoroughly with the corresponding study centers.

When a stem cell transplant is planned with a sibling as the donor, he or she should first undergo an ETV6 mutation analysis to rule out the possibility of being an asymptomatic carrier of the same genetic syndrome.

Surveillance Recommendations for the Early Detection of Cancer

Surveillance Recommendations

Since ETV6 deficiency is a very rare disease that has only been discovered recently, there is insufficient data to provide standardized surveillance recommendations. However, it is possible to state that the following examinations should be conducted on a regular basis:

  • Clinical examinations

  • Complete blood count once a year

  • Bone marrow puncture only with unstable blood values or clinically suspected leukemia

Self-Care and Support

What should I pay special attention to?

You should see a doctor as soon as you notice increased or hard-to-stop bleeding (e.g. nose or gum bleeding) or increased bruises. In addition, you should also go see a doctor right away if you are fatigued, feel sick, or have a fever, night sweats, pallor, frequent infections, or swollen lymph nodes. If you develop new anomalies or complaints, they should likewise be evaluated as soon as possible.

Support Groups and Additional Information

Unfortunately, we are as yet unaware of any existing support groups for patients with ETV6 deficiency. We will add new information as it becomes available.