How to Diagnose Fanconi Anemia

Fanconi anemia is a genetic disorder that originates from the bone marrow—the soft tissue inside bones responsible for blood cell production—that gets damaged. This damage disrupts blood cell generation and leads to severe health issues, including leukemia (a type of blood cancer). Though Fanconi anemia is a blood-related disorder, it can also affect other organs, tissues, and systems, increasing the risk of cancer. The disease is typically diagnosed before the age of 12, but it can also be detected during pregnancy or even before birth.

Investigate family genetic history. Since Fanconi anemia is hereditary, if someone in your family has a history of anemia, you might carry the gene and develop the disease. The condition arises from a recessive gene, meaning both parents must carry and pass on the gene to their child. Both parents can carry the gene without exhibiting symptoms themselves.

Undergoing Genetic Testing. If you're uncertain whether you carry the Fanconi anemia gene, you can seek genetic testing from a specialist. If neither parent carries the gene, the child will not inherit Fanconi anemia. However, if both parents carry the gene, there is a 1 in 4 chance that the child will develop the condition.

• The most common test is the gene mutation test. A geneticist will take a skin sample and examine any genetic mutations linked to Fanconi anemia.
• Chromosome breakage testing involves drawing a blood sample from the arm and applying special chemicals to treat the cells. The cells are then examined to see if they break apart. In Fanconi anemia, chromosomes tend to break and rearrange more easily than usual. This test is the only way to confirm whether you carry the Fanconi anemia gene. It is a complex test, and only a few centers can perform it.

Fetal Genetic Testing. Two tests are available for a developing fetus: chorionic villus sampling (CVS) and amniocentesis. Both tests are performed in a hospital setting.

• Chorionic villus sampling is done between 10-12 weeks after the mother's last menstrual period. A thin tube is inserted through the vagina and cervix to reach the placenta. The doctor gently suctions a sample of placental tissue for testing in the lab to detect genetic defects.
• Amniocentesis is performed between 15-18 weeks after the last menstrual period. The doctor uses a needle to collect a small amount of fluid surrounding the fetus. The technician then examines the chromosomes in the sample to check for genetic abnormalities.

Recognizing Symptoms of Fanconi Anemia. After the baby is born, check for physical abnormalities that could indicate Fanconi anemia. Some defects can be self-checked, while others require a doctor’s evaluation.

• Fanconi anemia can cause thumb abnormalities, such as the absence of the thumb, malformed thumbs, or more than three thumbs. The bones of the arms, hips, legs, hands, and feet may be underdeveloped or malformed. Children with Fanconi anemia may have scoliosis or a curved spine.
• The eyes, eyelids, and ears may also have abnormalities. A child with Fanconi anemia may experience hearing loss.
• Approximately 75% of children with Fanconi anemia have at least one physical defect at birth.
• Young children with Fanconi anemia may have kidney defects or kidney malformations.
• Fanconi anemia can lead to congenital heart defects, with the most common being a ventricular septal defect (VSD), which is a hole or defect in the wall separating the left and right ventricles of the heart.

Monitoring Skin Pigmentation Patches. Individuals with Fanconi anemia may notice light brown, flat patches of skin known as "café au lait" spots. These patches are named after the French term for "coffee with milk." Alternatively, the skin may show areas of lighter pigmentation (loss of skin color).

Observe Abnormalities in the Head and Face Area. These abnormalities may include a small or large head, a small lower jaw, a small face (bird-like shape), a sloped or protruding forehead, and more. Some patients may also have a low hairline and webbing around the neck.

• The eyes, eyelids, and ears may have deformities, which could lead to vision and hearing problems in those affected by Fanconi anemia.

Observe Bone Defects. The thumb may be missing or malformed. The arms, forearms, thighs, and legs may be short, curved, or misshapen. Hands and feet may have an unusual number of bones, and in some cases, there may be six fingers.

• The spine and vertebrae are common areas where bone defects occur. These defects can include scoliosis (curved spine), abnormal ribs and vertebrae, and extra vertebrae.

Recognize Genital Defects in Both Males and Females. Since males and females have different reproductive systems, it is important to be aware of the distinct signs for each.

• Genital defects in males may include underdevelopment of all genital organs, a small penis, undescended testes, hypospadias (an abnormal opening of the urethra on the underside of the penis), tight foreskin (abnormal tension preventing retraction of the foreskin), small testes, and infertility due to low sperm production.
• Genital defects in females may include absence of the vagina or uterus, a very narrow or underdeveloped vagina or uterus, and ovarian atrophy.

Identify Other Abnormalities in Development. Newborns may be underweight due to insufficient nutrition from the mother’s womb. The child may fail to develop at a normal rate, being smaller or shorter than their peers. Any form of anemia can result in inadequate oxygen supply to various tissues, causing malnutrition. The brain may also be underdeveloped, leading to a lower IQ or difficulties in learning.

Be Alert to Common Symptoms of Anemia. Fanconi anemia is a type of anemia and shares symptoms with many other conditions. People with these symptoms may not necessarily have Fanconi anemia, but it could be one of the causes.

• Fatigue is the primary symptom of anemia. The affected person feels tired due to reduced oxygen supply (needed for nutrient metabolism and energy production) in the cells.
• Anemia also involves a decrease in red blood cells (RBCs). The skin may appear pale because RBCs are responsible for giving the blood its red color, which in turn gives the skin a pinkish tone.
• Anemia causes the heart to work harder, increasing blood flow to other tissues to compensate for the lack of oxygen. This can lead to heart fatigue and eventually heart failure. In cases of heart failure, the patient may experience frothy coughing, shortness of breath (especially when lying down), or swelling.
• Other symptoms of anemia include dizziness, headaches (due to lack of oxygen reaching the brain), cold and pale skin, and weakness.

The white blood cells (WBC) form the body's natural defense system against a wide variety of infections. When bone marrow is impaired, the production of white blood cells decreases, weakening the body's protective barrier. As a result, children may become more susceptible to infections that a healthy immune system would usually fend off. Infected individuals tend to experience longer durations of illness and more difficulty in treating the condition.

• Children diagnosed with cancer at a young age should be screened for Fanconi anemia.

Platelets are essential for the clotting process, and a shortage of platelets can lead to prolonged bleeding even from small cuts and wounds. Young children are also more prone to bruising or developing petechiae, which are tiny red or purple spots on the skin caused by blood leaking from small blood vessels.

• If platelet levels drop significantly, bleeding may occur spontaneously from the nose, mouth, gastrointestinal tract, or within joints. This is a serious issue and requires urgent medical attention.

The symptoms mentioned above are only indications that you might be dealing with Fanconi anemia. Only a doctor has the necessary expertise to perform tests that confirm the diagnosis. Before undergoing any testing, it is crucial to inform the doctor about any existing health conditions that could affect the results. Additionally, sharing information about your family medical history, current medications, recent blood transfusions (if any), and other relevant health issues is important.

Fanconi anemia is a form of non-regenerative anemia, meaning the bone marrow is damaged and fails to produce enough blood cells. To perform the test, a doctor will use a needle to take a blood sample from your arm. This sample will then be analyzed under a microscope for a complete blood count (CBC) or a reticulocyte count.

• In a CBC test, the blood sample is spread on a slide and examined under a microscope. The doctor will count the number of cells to ensure there are sufficient red blood cells, white blood cells, and platelets. To identify non-regenerative anemia, the doctor will examine red blood cells to check for significant reductions in cell count, increased cell size, and unusual cell shapes.
• In a reticulocyte count test, the doctor will look at the blood sample under a microscope and count the reticulocytes. These are the direct precursors to red blood cells. The percentage of reticulocytes in the blood indicates how effectively the bone marrow is producing blood cells. In patients with non-regenerative anemia, this percentage will be significantly reduced, almost close to zero.

The process of analyzing cells through flow cytometry involves collecting a few cells from the skin and culturing them in a chemical environment. If the cells carry the Fanconi anemia gene, their growth will halt at an abnormal stage, which the lab specialist can easily identify under a microscope.

Bone marrow aspiration involves extracting a small amount of bone marrow for testing. After numbing the skin with a local anesthetic, the doctor inserts a thick, wide needle into the bone, usually in the tibia, upper sternum, or pelvic bone.

• For children or patients who are difficult to control, anesthesia may be used to make them sleep before the bone marrow aspiration.
• Even with anesthesia, the patient will still experience considerable pain as there are many nerves within the bone that a normal needle cannot reach with local anesthesia.
• Once the needle reaches a certain depth, the doctor attaches a syringe to the needle and gently pulls back the plunger. The yellow fluid drawn out is bone marrow, which will be tested to check if enough blood cells are being produced. The pain typically subsides once the needle is removed.
• Occasionally, the marrow may become thickened or fibrous due to prolonged inactivity. In such cases, no yellow fluid can be extracted, a condition known as a 'dry tap.'

In cases of 'dry tap,' the doctor may recommend a bone marrow biopsy to further investigate the marrow's condition. This procedure is similar to the bone marrow aspiration but uses a larger needle to extract a small sample of bone marrow tissue. The tissue is then examined under a microscope to assess the percentage of damaged cells.

• Do not confuse Fanconi anemia with Fanconi syndrome, a disorder affecting the kidneys.
• It is important to note that Fanconi anemia can be difficult to diagnose. As there are many other conditions that can cause anemia, diagnosing Fanconi anemia can be challenging. Although it is a blood disorder, it affects many other organs in the body and can produce more prominent symptoms.
• Fanconi anemia is associated with several other conditions and diseases. If diagnosed with Fanconi anemia, you may also have leukemia, other cancers, kidney disease, or heart defects.
• A bone marrow transplant can help treat Fanconi anemia. This is a common treatment for non-regenerative anemia cases. However, the preparation for a Fanconi anemia patient differs from that of other non-regenerative anemia patients. Those with Fanconi anemia will require different chemotherapy and radiation treatment than those with other non-regenerative anemias. Therefore, this treatment should be applied with caution.