ETV6 deficiency or thrombocytopenia 5 (OMIM #616216) is a genetic disease caused by mutations in the ETV6 gene. It is characterized by mild to moderate thrombocytopenia with or without a tendency to bleed, macrocytosis, and an increased risk of developing acute leukemia (especially B-ALL), myelodysplastic syndrome (MDS), and – more rarely – solid tumors.

Key Data

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Synonyms TEL deficiency, thrombocytopenia 5 with a predisposition to malignancy
Gene ETV6 (also TEL)
Gene product ETV6
Function Transcription factor, which plays an important role in hematopoiesis and embryonic development
Heredity Autosomal dominant
Prevalence Approximately 1% of B-ALL occur during childhood
Genotype-phenotype correlation Nearly all mutations occur in the ETS domain, which mediates DNA binding
Penetrance Approximately 25% develop acute leukemia and/or MDS.
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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 in the ETV6 gene.

Differential Diagnoses

  • Thrombocytopenia due to other causes

  • Hematological neoplasia with a different underlying mutation (e.g. RUNX1)

Clinical Presentation


  • Mild to moderate thrombocytopenia usually occurs in thrombocytes of normal size.

  • There is not always a tendency to bleed; it is usually mild to moderate, with a severe tendency to bleed occurring only rarely. Symptoms are usually epistaxis, bleeding gums, increased bruising, and menorrhagia.

  • Thrombocytopenia and a tendency to bleed may already manifest during infancy.

Hematological Diseases

  • Pre-B-All is the most common hematological malignancy, with an average onset at 7 years of age observed to date (age range of 2-37 years). However, cases of myeloid malignancy such as MDS, AML, and chronic myelomonocytic leukemia (CMML) have also been described.

  • Most patients have normal hemoglobin, and MCV is generally normal or elevated.

  • The bone marrow frequently exhibits immature hypolobated megakaryocytes, mild dyserythropoiesis, and mild nuclear hypolobation and hypogranulation of myeloid cells.

Additional Manifestations

  • In some patients, early-onset colorectal carcinomas have been reported.

  • The following tumors have been reported in a few cases: fibroadenoma of the breast, meningioma, mammary carcinoma, duodenal adenocarcinoma, and renal cell carcinoma.

Therapeutic Considerations

Mild to moderate thrombocytopenia without a tendency to bleed generally does not require any treatment. During childbirth or major operations, thrombocyte concentrates 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 an HLA-compatible 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

Surveillance Recommendations

The following examinations should be conducted regularly:

  • Clinical examinations

  • Complete blood count once a year

  • Bone marrow puncture only with unstable blood counts / clinically suspected leukemia

Additional Information

Open Clinical Trials / Registries

There are currently no open clinical trials/registries for patients with ETV6 deficiency that we can recommend to you for more information.

Support Groups

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.