Fanconi anaemiaa condition where there aren't enough red blood cells in the blood, causing fatigue, weakness and pale skin and affecting how the body responds to infection is a rare genetic disorder that is characterised by various physical abnormalities, bone marrowsoft, spongy tissue found in bones that makes blood cells failure and a predisposition to malignancy (cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs). It is classified as an inherited bone marrow failure syndrome (IBMFS), which is when the bone marrow is unable to produce enough healthy bloodthe red bodily fluid that transports oxygen and other nutrients around the body cellsthe basic structural and functional unit of all living things.
Blood is the bodily fluid of the circulatory system that provides nutrients and oxygen to our tissues, and helps to remove waste from our bodies. There are three primary types of blood cells produced in the inner, spongy portion of the bone (bone marrow) from stem cells (immature blood cells that develop into either red blood cells (RBCs), white blood cells (WBCs), or plateletssmall disc-shaped blood cells that clump together to form clots to stop bleeding). RBCs, or erythrocytes, are responsible for providing oxygen to the tissues in our body, as well as transporting carbon dioxide to the lungs to be exhaled. WBCs are responsible for fighting infectiona condition where harmful pathogens, such as bacteria, viruses or parasites, have entered the body and disease in the body. Platelets are blood cells that play a major role in blood clotting (or coagulation), which is an important process that helps reduce blood loss after injury.
Familial cancer syndromes, also known as hereditary cancer syndromes, are rare conditions that cause an increased riskthe possibility that something bad will happen of cancer as the result of inherited genetic mutations in certain cancer-related genes. They can affect both adults and children, however they generally develop in people at a younger age than normal. While familial cancer syndromes are not classified as cancer, they are equally as severe and can be life-threatening as they are associated with the development of various tumours throughout the body. Having a familial cancer syndrome does not guarantee the development of cancer, however the risk of developing cancer is higher than those who do not have a familial cancer syndrome.
Fanconi anaemia occurs when the bone marrow is damaged or not able to work properly, which reduces the capacity of the bone marrow to produce healthy RBCs, WBCs, and platelets. It is caused by a genetic mutation in one of at least 15 different genes.
Fanconi anaemia is slightly more common in males, and tends to be diagnosed before the age of 10. However, anyone can develop this disease.
Fanconi Anaemia Related Tumours
Fanconi anaemia is most commonly associated with the development of haematological cancers, most notably acutenew, recent, comes with an urgent or significant sense, is sudden, sharp myeloid leukaemiacancer of blood and/or blood forming tissues and myelodysplastic syndromes (MDS). However, it has also been linked to other types of tumours. Some examples include:
- Acute myeloid leukaemia (AML).
- Myelodysplastic syndromes (MDS).
- Head and neck squamous cell carcinomas.
- Skin cancer.
- Benignnot cancerous, can grow but will not spread to other body parts liver tumours,
- Liver cancer.
- Breast cancer.
- Breast cancer (Male).
- Oesophageal cancer.
- Oropharyngeal cancer.
- Vulvar cancer.
- Vaginal cancer.
- Cervical cancer.
- Anal cancer.
- Stomach (gastric) cancer.
- Colorectal (bowel) tumours.
- Brain tumours.
- Osteosarcoma.
- Retinoblastoma.
- Kidneya pair of bean-shaped organs in the abdomen that are responsible for filtering excess water and waste products from the blood and converting them into urine to be removed from the body cancer, potentially including:
- Lung cancer.
Treatment
When cancers are detected, they are staged and graded based on size, metastasiswhen the cancer has spread to other parts of the body, also known as mets, and how the cancer cells look under the microscope. Stagingthe process of determining how big the cancer is, where it started and if it has spread to other areas and grading help your doctors determine the best treatment for you. However, each patient with Fanconi anaemia will present with a unique disease behaviour, with varying tumoura tissue mass that forms from groups of unhealthy cells locations and symptoms. As such, there is no one treatment method that will work for everyone, and there is no standard staging system for this disease. Instead of staging and grading, your doctor will recommend a treatment plan based on the following factors:
- Type of tumours present.
- Whether the tumours are malignantcancerous, may grow and spread to other areas of the body (cancerous) or benign (non-cancerous).
- Tumour location.
- Whether or not malignant tumours have metastasised.
- Your age.
- General health.
- Your treatment preferences.
Your doctor may also recommend genetic testinga procedure that analyses DNA to identify changes in genes, chromosomes and proteins, which can be used to analyse tumour DNA to help determine which treatment has the greatest chance of success, which analyses your tumour DNA and can help determine which treatment has the greatest chance of success. They will then discuss the most appropriate treatment option for you.
Treatment options for tumours associated with Fanconi anaemia may include:
- Surgerytreatment involving removal of cancerous tissue and/or tumours and a margin of healthy tissue around it to reduce recurrence to remove as much of the tumour(s) as possible – these will vary based on tumour type and location.
- Chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells (limited).
- Radiation therapya treatment that uses controlled doses of radiation to damage or kill cancer cells (limited).
- Stem cell transplanta procedure that involves replacing unhealthy blood-forming cells (stem cells) with healthy stem cells.
- Hormone therapymedication that alters the levels of certain hormones in the body, such as oestrogen and progesterone.
- Targeted therapymedication that targets specific molecular features of cancer cells.
- Clinical trialsresearch studies performed to test new treatments, tests or procedures and evaluate their effectiveness on various diseases.
- Palliative carea variety of practices and exercises used to provide pain relief and improve quality of life without curing the disease.
Treatment for Fanconi Anaemia and Fertility
Treatment for some of the cancers associated with Fanconi anaemia may make it difficult to become pregnant. If fertility is important to you, discuss your options with your doctor prior to the commencement of treatment.
Cancer Screening
Once a diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results of Fanconi anaemia has been confirmed, implementing a targeted screeningtesting for cancer or conditions that can lead to cancer before symptoms appear, also known as cancer screening plan becomes essential due to the increased risk of developing certain cancers. The content of this plan will vary from person to person based on the genetic mutation involved, your family’s history of cancer and the types of cancers that may be present. It will also outline the routine tests you should have and how regularly you should have them.
Screening options for may evolve as new technologies are developed and our understanding of the condition grows. It is essential to discuss your individual circumstances with your healthcare team to determine the most appropriate screening plan for you.
Risk factors
In most cases, Fanconi anaemia is caused by a genetic mutation in FANCA (Fanconi anaemia, complementation group A), which is a protein coding gene that is involved in DNA repair. However, other genes can potentially also cause the disease, such as:
- FANCB (Fanconi anaemia complementation group B, involved in DNA repair).
- FANCC (Fanconi anaemia complementation group C, involved in DNA repair).
- FANCD (Fanconi anaemia complementation group D, involved in DNA repair).
- FANCE (Fanconi anaemia complementation group E, involved in DNA repair).
- FANCF (Fanconi anaemia complementation group F, involved in DNA repair).
- FANCG (Fanconi anaemia complementation group G, involved in DNA repair).
- FANCI (Fanconi anaemia complementation group I, involved in DNA repair).
- BRAC1 (breast cancer gene 1, tumour suppressor gene).
- BRCA2 (breast cancer gene 2, tumour suppressor gene).
- BRIP1 (BRCA1 interacting protein C-terminal helicase 1, tumour suppressor gene).
- ERCC4 (excisionto surgically remove/cut out repair cross-complementation group 1, DNA repair gene).
- FANCL (Fanconi anaemia complementation group L, involved in DNA repair).
- FANCM (Fanconi anaemia complementation group M, involved in DNA repair).
- PALB2 (partner and localiser of BRCA2, tumour suppressor gene).
- RAD51C (RAD51 paralog C, tumour suppressor gene).
- FANCP (Fanconi anaemia complementation group P, involved in DNA repair).
- UBE2T (ubiquitin-conjugating enzyme 2 T, involved in DNA repair).
- XRCC2 (x-raya type of medical imaging that uses x-ray beams to create detailed images of the body repair cross complementing gene 2, involved in DNA repair).
- FANCV (Fanconi anaemia complementation group V, involved in DNA repair).
In most cases, Fanconi anaemia is inherited as an autosomal recessive disorder, which means that you have to inherit one gene with the mutation from both parents in order to develop the condition. If both of parents carry the gene, there is a one in four chance of a child having the condition. However, there are two exceptions:
- FANCB gene (X-linked recessive).
- RAD51 gene (autosomal dominant).
People with the FANCB genetic mutation have an X-linked recessive disorder, which means that the mutation is found on the X chromosome. This type of inheritance tends to affect males more than females, as they only have one X chromosome. Comparatively, females carrying the mutation in one X chromosome tend to be unaffected, as they have two X chromosomes.
People with the RAD51 genetic mutation have an autosomal dominant disorder, which means that you have a 50% chance of developing the condition if one of your parents carries the mutation.
Not everyone with these risk factors will develop the disease, and some people who have the disease may have none of these risk factors. See your general practitioner (GP) if you are concerned.
Symptoms
The symptoms of Fanconi anaemia often vary by the type(s) of tumours present. General symptoms of Fanconi anaemia may include:
- Short stature.
- Limb abnormalities, potentially including:
- Extra, misshaped or missing fingers and/or thumbs.
- Incompletely developed/missing radial bone in the forearm.
- Genital abnormalities in males, potentially including:
- Underdeveloped genitalia.
- Undescended testicles.
- Hypospadias (a condition where the urethral opening isn’t at the tip of the penis).
- Atresia of the uterus, vagina and/or ovaries (one or both).
- Genital abnormalities in females, potentially including:
- Underdeveloped genitalia.
- Irregularly shaped uterus.
- Atresia of the uterus, vagina and/or ovaries (one or both).
- Skeletal abnormalities of the hips, spine and/or ribs.
- Structural issues with the kidneys.
- Abnormal skin pigmentation.
- Anaemia, which carries its own set of symptoms:
- Fatiguea state of extreme tiredness or exhaustion, can be physical or mental.
- Dizziness.
- Paleness.
- Dyspneadifficulty breathing, shortness of breath.
- Abnormally small head.
- Small, crossed or widely spaced eyes.
- Low birth weight.
- Difficulties with vision and/or hearing.
- Gastrointestinal difficulties.
Symptoms related to specific tumours can be found on our knowledgebase.
Not everyone with the symptoms above will have cancer, but see your general practitioner (GP) if you are concerned.
Diagnosis
If your doctor suspects you have tumours associated with Fanconi anaemia, they may order some of the following tests to confirm the diagnosis and refer you to a specialist for treatment. The tests required for diagnosis will often vary based on the symptoms present, and where the tumour(s) are suspected to be located.
- Physical examinationan examination of your current symptoms, affected area(s) and overall medical history.
- Genetic testing.
- Pelvic examinationa physical exam of the external and internal female pelvic organs.
- Digital rectal examinationan examination conducted by a urologist where a finger (or digit) is inserted into the rectum to feel the anus (DRE).
- Blood teststesting done to measure the levels of certain substances in the blood.
- Imagingtests that create detailed images of areas inside the body tests, potentially including:
- Ultrasounda type of medical imaging that uses soundwaves to create detailed images of the body .
- MRI (magnetic resonance imaging)a type of medical imaging that uses radiowaves, a strong magnet and computer technology to create detailed images of the body.
- Lumbar puncturea procedure that involves inserting a needle between two vertebrae in the lower spine and extracting a sample of cerebrospinal fluid (CSF) for analysis.
- Bone marrow aspirationa procedure that involves inserting a needle into the hipbone (or the breastbone in some cases) to remove samples of solid and liquid bone marrow.
- Exploratory procedures, such as an endoscopya procedure that involves inserting a long, flexible tube with a light and small camera (endoscope) into the body to view internal organs.
- Biopsyremoval of a section of tissue to analyse for cancer cells.