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Familial platelet disorder with AML predisposition
FPD/AML is a rare inherited disorder that primarily affects blood-clotting and can lead to difficulties with bleeding. Individuals with FPD/AML also have a significantly higher chance of developing a type of blood cancer called acute myeloid leukaemia (AML).
Overview
Familial platelet disorder with AML predisposition (FPD/AML) is a rare inherited condition. It typically involves a reduced number of platelets in the blood (thrombocytopenia) and platelets that do not work as they should (platelet dysfunction). Platelets are crucial for normal blood clotting, so individuals with FPD/AML may experience easy bruising or prolonged bleeding [PMID:33678082]. A key feature of FPD/AML is a significantly increased lifetime risk of developing acute myeloid leukaemia (AML), a serious type of blood cancer.
Symptoms & clinical features
The symptoms of FPD/AML can vary widely among affected individuals, even within the same family. Bleeding is a common concern due to the issues with platelets. This might manifest as easy bruising, nosebleeds, gum bleeding, or heavy menstrual periods in women. Some individuals may have no noticeable bleeding problems, while others might experience more severe episodes, particularly after injury or surgery [PMID:17967919]. The leukaemia associated with FPD/AML is typically acute myeloid leukaemia (AML). Signs of AML can include fatigue, fever, unexplained weight loss, and recurrent infections.
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Affected organs
FPD/AML primarily affects the bone marrow, which is the soft tissue inside bones where blood cells, including platelets, are produced. The condition disrupts the normal production and function of platelets. Over time, the malfunctioning bone marrow can lead to the development of acute myeloid leukaemia, a cancer of the blood-forming cells. Other organs are not directly affected by FPD/AML itself, but complications from bleeding or leukaemia can impact various body systems.
Risks & severity
The severity of FPD/AML symptoms, particularly bleeding, can range from mild to significant. Some individuals may experience few problems, while others require close monitoring. A major concern is the elevated lifetime risk of developing acute myeloid leukaemia (AML). Research suggests that approximately one-third to one-half of individuals with FPD/AML will develop AML, often in adulthood [PMID:11599026]. The risk of AML can be as high as 60% in certain families. Therefore, regular monitoring is an important part of managing the condition to detect early signs of AML. The precise age of onset for AML varies but typically occurs in early to middle adulthood.
Genetic causes
Familial platelet disorder with AML predisposition is caused by pathogenic variants in the RUNX1 gene. The RUNX1 gene provides instructions for making a protein called RUNX1, which is a transcription factor. Transcription factors are proteins that help control which genes are turned on or off in a cell. The RUNX1 protein is essential for the normal development and maturation of blood cells, particularly in the bone marrow. When there is a pathogenic change in RUNX1, it disrupts the normal regulation of blood cell production, leading to problems with platelet number and function, and increasing the risk of developing AML.
- RUNX1 RUNX family transcription factor 1
Inheritance pattern
FPD/AML is inherited in an autosomal dominant pattern. This means that a person only needs to inherit one copy of the altered RUNX1 gene from an affected parent to develop the condition. If a parent has FPD/AML, there is a 50% chance with each pregnancy that their child will also inherit the condition. FPD/AML can also arise from a new (de novo) pathogenic variant in the RUNX1 gene in an individual, with no family history. In such cases, the affected individual may then pass the condition on to their children.
Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.
Diagnosis & testing
Diagnosing FPD/AML typically begins with a clinical suspicion based on a personal or family history of low platelet counts, unusual bleeding, or a diagnosis of AML. Blood tests showing reduced platelet numbers and/or impaired platelet function may suggest the condition. A definitive diagnosis is confirmed through genetic testing to identify a pathogenic variant in the RUNX1 gene [PMID:33678082]. This testing is usually performed on a blood sample. In the UK, individuals with suspected FPD/AML may be referred to a clinical genetics service or a haematologist, who can coordinate appropriate investigations. Genetic testing for FPD/AML is available through the NHS Genomic Medicine Service, often under specific R-codes for inherited bone marrow failure syndromes.
Management & lifestyle
Management of FPD/AML focuses on monitoring for complications, particularly the development of acute myeloid leukaemia, and managing bleeding symptoms. Regular haematological surveillance, which might include blood counts and bone marrow examinations, is typically recommended to detect early signs of AML. Individuals should avoid medications that can worsen bleeding, such as aspirin, unless prescribed by a doctor. For bleeding episodes, treatments might include platelet transfusions or certain medications to enhance clotting. Should AML develop, treatment would follow standard oncology protocols. Genetic counselling is an important part of the management pathway, offering support and information to affected individuals and their families about the condition, inheritance patterns, and reproductive options. This information is intended for educational purposes and is not a substitute for professional medical advice.
UK care pathway
In the UK, individuals suspected of having FPD/AML would typically be referred to a clinical genetics service or a specialist haematologist. These specialists can arrange appropriate diagnostic genetic testing, which is available via the NHS Genomic Medicine Service. The specific genetic test may be identified by an R-code, relevant to inherited bone marrow failure syndromes. Genetic counsellors play a vital role, providing information, support, and discussions about the implications of a genetic diagnosis for the individual and their wider family.
Frequently asked questions
What is the likelihood of my child inheriting FPD/AML if I have it?
Because FPD/AML is inherited in an autosomal dominant pattern, there is a 50% chance with each pregnancy that your child will inherit the altered RUNX1 gene and therefore the condition. Genetic counselling can provide more personalised risk assessments.
Can FPD/AML be prevented?
FPD/AML is a genetic condition caused by specific changes in the RUNX1 gene, so its inheritance cannot be prevented. However, regular monitoring and appropriate medical care can help manage symptoms and detect complications, such as leukaemia, early.
What kind of monitoring is needed for FPD/AML?
Individuals with FPD/AML typically require regular check-ups with a haematologist. This usually involves frequent blood tests to monitor platelet counts and overall blood cell health. Sometimes, bone marrow examinations may also be recommended to look for early signs of leukaemia.
Is everyone with a RUNX1 gene change guaranteed to develop leukaemia?
No, not everyone with a pathogenic RUNX1 variant will develop leukaemia. While there is a significantly increased lifetime risk, typically around one-third to one-half of affected individuals develop acute myeloid leukaemia, meaning many will not. Regular monitoring helps to identify any signs early.
Are there challenges in pregnancy for women with FPD/AML?
Women with FPD/AML may experience increased bleeding risks during pregnancy and childbirth due to their platelet issues. Careful management by a haematologist and obstetrician throughout pregnancy is often necessary to minimise these risks and ensure a safe delivery for both mother and baby.