"ETV6 Deficiency" – What Is It?
ETV6 deficiency, also known as thrombocytopenia 5, is a disease caused by mutations, i.e., genetic changes in the ETV6 gene. Characteristic features are a reduced quantity of blood platelets (thrombocytopenia) with or without a tendency to bleed, an enlargement of the red blood cells (macrocytosis), and an increased risk of developing acute leukemia (especially B-ALL), myelodysplastic syndrome (MDS, a disease of the bone marrow) and, rarely, other tumors.
How Is "ETV6 Deficiency" Diagnosed?
Suspected Diagnosis
If there is a family history of mild to moderate thrombocytopenia or a combination of thrombocytopenia and leukemia or solid tumor, an ETV6 mutation should be considered and genetically tested for.
Genetic Diagnostics
The diagnosis of “ETV6 deficiency” is confirmed by the detection of a mutation, i.e., a genetic change in the ETV6 gene.
What Is the Risk of Cancer?
Around 25% of patients with an ETV6 mutation develop acute leukemia or MDS. The most common malignant disease of the hematopoietic system (hematological malignancy) is pre-B-ALL (acute lymphoblastic leukemia of the B-cell lineage), which in previous observations occurred on average at the age of 7 years (age range 2-37 years). However, other hematological malignancies have also been described, such as MDS, AML (acute myeloid leukemia), and chronic myelomonocytic leukemia (CMML).
In addition to diseases of the hematopoietic system, other malignant tumors also occur in the context of an ETV6 mutation. Early-onset colon cancer has been reported in some patients, and breast cancer, meningioma (a brain tumor), small bowel cancer, and kidney cancer have been observed in isolated cases.
In addition to the increased risk of cancer, mild to moderate thrombocytopenia often occurs. A bleeding tendency is not always present, it is usually also mild to moderate, only rarely is there a strong bleeding tendency. Symptoms typically include nose and/or gum bleeding, increased bruising, and prolonged menstrual bleeding. Thrombocytopenia and a tendency to bleed can manifest themselves as early as infancy.
What Is Known About the Development of "ETV6 Deficiency"?
ETV6 deficiency is caused by a mutation, i.e., a genetic change in the ETV6 gene. This gene codes for the so-called transcription factor ETV6, which plays an important role in the development of blood cells. If the ETV6 gene is present in an altered form, the transcription factor can no longer function correctly, and leukemia develops.
ETV6 deficiency can be passed on from parents to their children. The inheritance is autosomal dominant.
Is There Any Form of Treatment Available?
Mild to moderate thrombocytopenia without a tendency to bleed does not usually require treatment. In the event of childbirth or major surgery, appropriate blood products should be available and given in the event of more severe bleeding.
The treatment of MDS or leukemia in patients with an ETV6 mutation should be discussed with the relevant study centers.
If a stem cell transplant is planned with a sibling as the donor, an ETV6 mutation analysis should be carried out beforehand to rule out the possibility that the sibling is a previously unknown carrier of the same genetic syndrome.
Diagnosis of " ETV6 Deficiency" What's Next?
If you have been diagnosed with this cancer predisposition syndrome, it is important to see a specialist. The following section explains whether cancer screening tests or other measures are needed and how they should be carried out. We also give you some valuable tips on what you can do yourself. If you have any questions, please do not hesitate to contact us or your doctor.
Diagnosis of " ETV6 Deficiency" What's Next?
If you have been diagnosed with this cancer predisposition syndrome, it is important to see a specialist. The following section explains whether cancer screening tests or other measures are needed and how they should be carried out. We also give you some valuable tips on what you can do yourself. If you have any questions, please do not hesitate to contact us or your doctor.
Medical Measures for Early Detection
In the case of ETV6 deficiency, the patient should be referred to a centre where appropriate haemato-oncological care and genetic counselling can be provided.
The following screening measures should be carried out:
- Regular clinical assessments (at least annually, every 3-6 months if at higher risk of MDS/AML)
- A differential blood count every 6-12 months
- Sampling and examination of the bone marrow every 1-3 years (depending on the findings)
- ETV6 deficient patients, their families and their physicians should be aware of suspicious clinical symptoms that may indicate the development of leukaemia
- Family history should be regularly updatet with regard to new body tissue/tumour formation, reduced blood cell count and bleeding
ETV6 Deficiency – What You Can Do Yourself
You should pay attention to the following
You should consult a doctor when you notice increased or difficult-to-stop bleeding (e.g., prolonged or frequent nosebleeds) or increased bruising. You should also urgently consult a doctor if you feel tired or ill, have a fever, night sweats, paleness, frequent infections, or swelling of the lymph nodes. If there are any other new abnormalities or complaints, these should also be clarified as soon as possible.
Further Information
Unfortunately, we are not yet aware of any support groups for patients with ETV6 deficiency. As soon as we have new information, we will add it here. However, patients can also register for the CPS register at any time or have this done by the doctors looking after them.
Any further questions?
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