What is RUNX1 deficiency?

RUNX1 deficiency or familial platelet disorder with associated myeloid malignancy (FPDMM, OMIM #601399) is a disease caused by mutations – or genetic changes – in the RUNX1 gene. Characteristic features include a reduced amount of blood platelets (thrombocytopenia) and defective blood platelet function (thrombocytopathy) associated with increased, hard-to-stop bleeding. In addition, there is an increased risk that malignant new formations of the blood-formation system (hematological neoplasia) will develop, such as myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), or acute T-cell leukemia (T-ALL). The severity of the clinical signs varies widely.

How is RUNX1 deficiency diagnosed?

Suspected Diagnosis

The existence of a mutation in the RUNX1 gene is suspected whenever no other cause can be found for patients with chronic thrombocytopenia or thrombocyte function disorder. It is also indicated when family members are known to be suffering from bleeding, thrombocytopenia, thrombocytopathy, or hematological neoplasia. However, it must be borne in mind that symptoms of a RUNX1 mutation can vary greatly even within the same family: For example, while one person may have frequent nose bleeds as his or her only symptom, someone else in the same family may develop AML.

Genetic Diagnostics

The diagnosis of “RUNX1 deficiency” is confirmed by detection of a mutation – or a genetic change – in the RUNX1 gene.

What is the risk of cancer?

Malignant Diseases of the Blood-Formation System

The risk of developing malignant hematological neoplasia (MDS or AML) is 30-40%. It is also possible for T-ALL to develop.

The average age of onset for MDS or AML is 33, although the age range is broad. T-ALL as part of a RUNX1 mutation generally occurs earlier.

Thrombocytopenia and Thrombocytopathy

Mild to moderate thrombocytopenia along with low-normal to normal range thrombocyte values are possible. The severity of bleeding resulting from thrombocytopenia and thrombocyte functional defects varies greatly.

What causes RUNX1 deficiency?

RUNX1 deficiency is caused by a mutation – or genetic change – in the RUNX1 gene. This gene encodes for the RUNX1 transcription factor, which plays an important role in the development of blood cells. Now if the RUNX1 gene is altered, the transcription factor will no longer be able to function properly, resulting in the development of hematological neoplasia.

The RUNX1 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?

Treatment of MDS or AML in patients with a RUNX1 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 a RUNX1 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

FPDMM patients should be in the care of a center where they can receive adequate hemato-oncological care and genetic counseling.

The following surveillance measures for early detection should be included:

  • Regular clinical examinations (at least annually, and every 3-6 months when there is a higher risk of MDS/AML)

  • Differential blood count (initially every 3-4 months, which can be extended to every 6-12 months with stable findings, and every 2-4 weeks when there are abnormalities)

  • Bone marrow puncture to detect early signs of developing hematological neoplasia (annually, and more often when there are abnormalities in the blood count)

  • FPDMM patients, their families, and their attending physician should be familiar with suspicious clinical symptoms that indicate the development of leukemia.

  • Any new developments, changes in the blood count, and bleeding that occur in the family should be registered, documented, and regularly updated.

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, are pale, suffer from frequent infections, or if you have swollen lymph nodes. If you develop new anomalies or complaints, these 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 RUNX1 deficiency. We will add new information as it becomes available.