"RUNX1 Deficiency" – What Is It?
RUNX1 deficiency or familial platelet disorder with associated myeloid malignancy (FPDMM) is a disease caused by mutations, i.e., genetic changes in the RUNX1 gene. Characteristic features are reduced blood platelets (thrombocytopenia) and defective platelet function (thrombocytopathy), which are associated with increased bleeding that is difficult to stop. In addition, there is an increased risk of developing malignant neoplasms of the hematopoietic system (hematological neoplasms), such as myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) or acute T-cell leukemia (T-ALL). The degree of clinical manifestation is highly variable.
How Is "RUNX1 Deficiency" Diagnosed?
Suspected Diagnosis
In patients with persistent thrombocytopenia or platelet dysfunction for which no other cause could be found, a mutation in the RUNX1 gene is suspected. In addition, bleeding, thrombocytopenia, thrombocytopathy, or hematologic neoplasia known in family members may be indicative. However, it must be noted that the symptoms of a RUNX1 mutation can vary greatly, even within a family. For example, while one person’s only symptom is frequent nosebleeds, another person in the same family develops AML.
Genetic Diagnostics
The diagnosis of “RUNX1 deficiency” is confirmed by the detection of a mutation, i.e., a genetic change in the RUNX1 gene.
What Is the Risk of Cancer?
Malignant Diseases of the Hematopoietic System
The risk of developing a malignant hematologic neoplasm (an MDS or an AML) is 30-40%. In addition, T-ALL may also develop.
The average age at the onset of MDS or AML is 33 years, albeit with a wide age range. T-ALL, in the context of a RUNX1 mutation, usually occurs earlier.
Thrombocytopenia and Thrombocytopathy
Low-normal to average platelet counts are also possible with mild to moderate thrombocytopenia. The severity of the bleeding resulting from thrombocytopenia and platelet dysfunction is highly variable.
What Is Known About the Development of "RUNX1 Deficiency "?
RUNX1 deficiency is caused by a mutation, i.e., a genetic change in the RUNX1 gene. This gene codes for the so-called transcription factor RUNX1, which plays an important role in the development of blood cells. If the RUNX1 gene is present in an altered form, the transcription factor can no longer function correctly, and hematological neoplasia develops.
RUNX1 deficiency can be passed on from parents to their children. The inheritance is autosomal dominant.
Is There Any Form of Treatment Available?
The treatment of MDS or AML in patients with a RUNX1 mutation should be discussed with the relevant study centers.
In the case of a planned stem cell transplant with a sibling as a donor, a RUNX1 mutation analysis should be performed on the sibling beforehand to rule out the possibility that he or she is a previously unknown carrier of the same genetic syndrome.
Diagnosis of " RUNX1 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 " RUNX1 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
FPDMM patients should be linked to a center where they can receive adequate hemato-oncological care and genetic counseling.
Folgendes sollten die Früherkennungsmaßnahmen beinhalten
- Regelmäßige klinische Untersuchungen (mindestens jährlich, bei höherem Risiko für MDS/AML alle 3-6 Monate)
- Differentialblutbild (zunächst alle 3-4 Monate, bei stabilen Befunden ausdehnbar auf alle 6-12 Monate, bei Auffälligkeiten alle 2-4 Wochen)
- Knochenmarkpunktion, um frühe Zeichen einer sich entwickelnden hämatologischen Neoplasie zu detektieren (jährlich, bei Auffälligkeiten im Blutbild in höherer Frequenz)
- FPDMM-Patient:innen, ihre Familien und ihre behandelnden Ärzt:innen sollten mit suspekten klinischen Symptomen, die auf die Entwicklung einer Leukämie hindeuten, vertraut sein.
- In der Familie auftretende Neubildungen, Veränderungen im Blutbild und Blutungen sollten registriert, dokumentiert und regelmäßig aktualisiert werden.
RUNX1 Deficiency – What You Can Do Yourself
You Should Pay Attention to This
You should consult a doctor as soon as you notice increased bleeding or bleeding that is difficult to stop (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, pallor, frequent infections, or swelling of the lymph nodes. These should also be clarified immediately if other new abnormalities or complaints occur.
Further Information
Unfortunately, we are unaware of any support groups for patients with RUNX1 deficiency. As soon as we have new information, we will add it here. However, patients can also register for the CPS registry at any time or have this done by their doctors in charge.
Any further questions?
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