For more information, visit http://www.nhlbi.nih.gov/health/health-topics/topics/fanconi/

What Causes Fanconi Anemia?

Fanconi anemia (FA) is an inherited disease. The term “inherited” means that the disease is passed from parents to children through genes. At least 13 faulty genes are associated with FA. FA occurs when both parents pass the same faulty FA gene to their child.

People who have only one faulty FA gene are FA "carriers." Carriers don't have FA, but they can pass the faulty gene to their children.

If both of your parents have a faulty FA gene, you have:

• A 25 percent chance of having FA
• A 25 percent chance of not having FA
• A 50 percent chance of being an FA carrier and passing the gene to any children you have

If only one of your parents has a faulty FA gene, you won't have the disorder. However, you have a 50 percent chance of being an FA carrier and passing the gene to any children you have.

Who Is at Risk for Fanconi Anemia?

Fanconi anemia (FA) occurs in all racial and ethnic groups and affects men and women equally.

In the United States, about 1 out of every 181 people is an FA carrier. This carrier rate leads to about 1 in 130,000 people being born with FA.

Two ethnic groups, Ashkenazi Jews and Afrikaners, are more likely than other groups to have FA or be FA carriers.

Ashkenazi Jews are people who are descended from the Jewish population of Eastern Europe. Afrikaners are White natives of South Africa who speak a language called Afrikaans. This ethnic group is descended from early Dutch, French, and German settlers.

In the United States, 1 out of 90 Ashkenazi Jews is an FA carrier, and 1 out of 30,000 is born with FA.

Major Risk Factors

FA is an inherited disease—that is, it's passed from parents to children through genes. At least 13 faulty genes are associated with FA. FA occurs if both parents pass the same faulty FA gene to their child.

Children born into families with histories of FA are at risk of inheriting the disorder. Children whose mothers and fathers both have family histories of FA are at even greater risk. A family history of FA means that it's possible that a parent carries a faulty gene associated with the disorder.

Children whose parents both carry the same faulty gene are at greatest risk of inheriting FA. Even if these children aren't born with FA, they're still at risk of being FA carriers.

Children who have only one parent who carries a faulty FA gene also are at risk of being carriers. However, they're not at risk of having FA.

What Are the Signs and Symptoms of Fanconi Anemia?

Major Signs and Symptoms

Your doctor may suspect you or your child has Fanconi anemia (FA) if you have signs and symptoms of:

• Anemia
• Bone marrow failure
• Birth defects
• Developmental or eating problems

FA is an inherited disorder—that is, it's passed from parents to children through genes. If a child has FA, his or her brothers and sisters also should be tested for the disorder.

Anemia

The most common symptom of all types of anemia is fatigue (tiredness). Fatigue occurs because your body doesn't have enough red blood cells to carry oxygen to its various parts. If you have anemia, you may not have the energy to do normal activities.

A low red blood cell count also can cause shortness of breath, dizziness, headaches, coldness in your hands and feet, pale skin, and chest pain.

Bone Marrow Failure

When your bone marrow fails, it can't make enough red blood cells, white blood cells, and platelets. This can cause many problems that have various signs and symptoms.

With too few red blood cells, you can develop anemia. In FA, the size of your red blood cells also can be much larger than normal. This makes it harder for the cells to work well.

With too few white blood cells, you're at risk for infections. Infections also may last longer and be more serious than normal.

With too few platelets, you may bleed and bruise easily, suffer from internal bleeding, or have petechiae (pe-TEE-kee-ay). Petechiae are tiny red or purple spots on the skin. Bleeding in small blood vessels just below your skin causes these spots.

In some people who have FA, the bone marrow makes a lot of harmful, immature white blood cells called blasts. Blasts don't work like normal blood cells. As they build up, they prevent the bone marrow from making enough normal blood cells.

A large number of blasts in the bone marrow can lead to a type of blood cancer called acute myeloid leukemia (AML).

Birth Defects

Many birth defects can be signs of FA. These include:

• Bone or skeletal defects. FA can cause missing, oddly shaped, or three or more thumbs. Arm bones, hips, legs, hands, and toes may not form fully or normally. People who have FA may have a curved spine, a condition called scoliosis (sco-le-O-sis).
• Eye and ear defects. The eyes, eyelids, and ears may not have a normal shape. Children who have FA also might be born deaf.
• Skin discoloration. This includes coffee-colored areas or odd-looking patches of lighter skin.
• Kidney problems. A child who has FA might be born with a missing kidney or kidneys that aren't shaped normally.
• Congenital heart defects. The most common congenital heart defect linked to FA is a ventricular septal defect (VSD). A VSD is a hole or defect in the lower part of the wall that separates the heart’s left and right chambers.

Developmental Problems

Other signs and symptoms of FA are related to physical and mental development. They include:

• Low birth weight
• Poor appetite
• Delayed growth
• Below-average height
• Small head size
• Mental retardation or learning disabilities

Signs and Symptoms of Fanconi Anemia in Adults

Some signs and symptoms of FA may develop as you or your child gets older. Women who have FA may have some or all of the following:

• Sex organs that are less developed than normal
• Menstruating later than women who don't have FA
• Starting menopause earlier than women who don't have FA
• Problems getting pregnant and carrying a pregnancy to full term

Men who have FA may have sex organs that are less developed than normal. They also may be less fertile than men who don't have the disease. 

How Is Fanconi Anemia Diagnosed?

People who have Fanconi anemia (FA) are born with the disorder. They may or may not show signs or symptoms of it at birth. For this reason, FA isn't always diagnosed when a person is born. In fact, most people who have the disorder are diagnosed between the ages of 2 and 15 years.

The tests used to diagnose FA depend on a person's age and symptoms. In all cases, medical and family histories are an important part of diagnosing FA. However, because FA has many of the same signs and symptoms as other diseases, only genetic testing can confirm its diagnosis.

Specialists Involved

A geneticist is a doctor or scientist who studies how genes work and how diseases and traits are passed from parents to children through genes.

Geneticists do genetic testing for FA. They also can provide counseling about how FA is inherited and the types of prenatal (before birth) testing used to diagnose it.

An obstetrician may detect birth defects linked to FA before your child is born. An obstetrician is a doctor who specializes in providing care for pregnant women.

After your child is born, a pediatrician also can help find out whether your child has FA. A pediatrician is a doctor who specializes in treating children and teens.

A hematologist (blood disease specialist) also may help diagnose FA.

Family and Medical Histories

FA is an inherited disease. Some parents are aware that their family has a medical history of FA, even if they don't have the disease.

Other parents, especially if they're FA carriers, may not be aware of a family history of FA. Many parents may not know that FA can be passed from parents to children.

Knowing your family medical history can help your doctor diagnose whether you or your child has FA or another condition with similar symptoms.

If your doctor thinks that you, your siblings, or your children have FA, he or she may ask you detailed questions about:

• Any personal or family history of anemia
• Any surgeries you’ve had related to the digestive system
• Any personal or family history of immune disorders
• Your appetite, eating habits, and any medicines you take

If you know your family has a history of FA, or if your answers to your doctor's questions suggest a possible diagnosis of FA, your doctor will recommend further testing.

Diagnostic Tests and Procedures

The signs and symptoms of FA aren't unique to the disease. They're also linked to many other diseases and conditions, such as aplastic anemia. For this reason, genetic testing is needed to confirm a diagnosis of FA. Genetic tests for FA include the following.

Chromosome Breakage Test

This is the most common test for FA. It's available only in special laboratories (labs). It shows whether your chromosomes (long chains of genes) break more easily than normal.

Skin cells sometimes are used for the test. Usually, though, a small amount of blood is taken from a vein in your arm using a needle. A technician combines some of the blood cells with certain chemicals.

If you have FA, the chromosomes in your blood sample break and rearrange when mixed with the test chemicals. This doesn't happen in the cells of people who don't have FA.

Cytometric Flow Analysis

Cytometric flow analysis, or CFA, is done in a lab. This test examines how chemicals affect your chromosomes as your cells grow and divide. Skin cells are used for this test.

A technician mixes the skin cells with chemicals that can cause the chromosomes in the cells to act abnormally. If you have FA, your cells are much more sensitive to these chemicals.

The chromosomes in your skin cells will break at a high rate during the test. This doesn't happen in the cells of people who don't have FA.

Mutation Screening

A mutation is an abnormal change in a gene or genes. Geneticists and other specialists can examine your genes, usually using a sample of your skin cells. With special equipment and lab processes, they can look for gene mutations that are linked to FA.

Diagnosing Different Age Groups

Before Birth (Prenatal)

If your family has a history of FA and you get pregnant, your doctor may want to test you or your fetus for FA.

Two tests can be used to diagnose FA in a developing fetus: amniocentesis (AM-ne-o-sen-TE-sis) and chorionic villus (ko-re-ON-ik VIL-us) sampling (CVS). Both tests are done in a doctor's office or hospital.

Amniocentesis is done 15 to 18 weeks after a pregnant woman's last period. A doctor uses a needle to remove a small amount of fluid from the sac around the fetus. A technician tests chromosomes (chains of genes) from the fluid sample to see whether they have faulty genes associated with FA.

CVS is done 10 to 12 weeks after a pregnant woman's last period. A doctor inserts a thin tube through the vagina and cervix to the placenta (the temporary organ that connects the fetus to the mother).

The doctor removes a tissue sample from the placenta using gentle suction. The tissue sample is sent to a lab to be tested for genetic defects associated with FA.

At Birth

Three out of four people who inherit FA are born with birth defects. If your baby is born with certain birth defects, your doctor may recommend genetic testing to confirm a diagnosis of FA.

For more information about these defects, go to “What Are the Signs and Symptoms of Fanconi Anemia?”

Childhood and Later

Some people who have FA are not born with birth defects. Doctors may not diagnose them with the disorder until signs of bone marrow failure or cancer occur. This usually happens within the first 10 years of life.

Signs of bone marrow failure most often begin between the ages of 3 and 12 years, with 7 to 8 years as the most common ages. However, 10 percent of children who have FA aren't diagnosed until after 16 years of age.

If your bone marrow is failing, you may have signs of aplastic anemia. FA is one type of aplastic anemia.

In aplastic anemia, your bone marrow stops making or doesn't make enough of all three types of blood cells: red blood cells, white blood cells, and platelets.

Aplastic anemia can be inherited or acquired after birth through exposure to chemicals, radiation, or medicines.

Doctors diagnose aplastic anemia using:

• Family and medical histories and a physical exam.
• A complete blood count (CBC) to check the number, size, and condition of your red blood cells. The CBC also checks numbers of white blood cells and platelets.
• A reticulocyte (re-TIK-u-lo-site) count. This test counts the number of new red blood cells in your blood to see whether your bone marrow is making red blood cells at the proper rate.
• Bone marrow tests. For a bone marrow aspiration, a small amount of liquid bone marrow is removed and tested to see whether it's making enough blood cells. For a bone marrow biopsy, a small amount of bone marrow tissue is removed and tested to see whether it's making enough blood cells.

If you or your child is diagnosed with aplastic anemia, your doctor will want to find the cause. If your doctor suspects you have FA, he or she may recommend genetic testing.

For more information, go to the Health Topics Aplastic Anemia article.

How Is Fanconi Anemia Treated?

Doctors decide how to treat Fanconi anemia (FA) based on a person's age and how well the person's bone marrow is making new blood cells.

Goals of Treatment

Long-term treatments for FA can:

• Cure the anemia. Damaged bone marrow cells are replaced with healthy ones that can make enough of all three types of blood cells on their own.

—Or—

• Treat the symptoms without curing the cause. This is done using medicines and other substances that can help your body make more blood cells for a limited time.

Screening and Short-Term Treatment

Even if you or your child has FA, your bone marrow might still be able to make enough new blood cells. If so, your doctor might suggest frequent blood count checks so he or she can watch your condition.

Your doctor will probably want you to have bone marrow tests once a year. He or she also will screen you for any signs of cancer or tumors.

If your blood counts begin to drop sharply and stay low, your bone marrow might be failing. Your doctor may prescribe antibiotics to help your body fight infections. In the short term, he or she also may want to give you blood transfusions to increase your blood cell counts to normal levels.

However, long-term use of blood transfusions can reduce the chance that other treatments will work.

Long-Term Treatment

The four main types of long-term treatment for FA are:

• Blood and marrow stem cell transplant
• Androgen therapy
• Synthetic growth factors
• Gene therapy

Blood and Marrow Stem Cell Transplant

A blood and marrow stem cell transplant is the current standard treatment for patients who have FA that's causing major bone marrow failure. Healthy stem cells from another person, called a donor, are used to replace the faulty cells in your bone marrow.

If you're going to receive stem cells from another person, your doctor will want to find a donor whose stem cells match yours as closely as possible.

Stem cell transplants are most successful in younger people who:

• Have few or no serious health problems
• Receive stem cells from a brother or sister who is a good donor match  
• Have had few or no previous blood transfusions

During the transplant, you'll get donated stem cells in a procedure that's like a blood transfusion. Once the new stem cells are in your body, they travel to your bone marrow and begin making new blood cells.

A successful stem cell transplant will allow your body to make enough of all three types of blood cells.

Even if you've had a stem cell transplant to treat FA, you’re still at risk for some types of blood cancer and cancerous solid tumors. Your doctor will check your health regularly after the procedure.

For more information about stem cell transplants—including finding a donor, having the procedure, and learning about the risks—go to the Health Topics Blood and Marrow Stem Cell Transplant article.

Androgen Therapy

Before improvements made stem cell transplants more effective, androgen therapy was the standard treatment for people who had FA. Androgens are man-made male hormones that can help your body make more blood cells for long periods.

Androgens increase your red blood cell and platelet counts. They don't work as well at raising your white blood cell count.

Unlike a stem cell transplant, androgens don't allow your bone marrow to make enough of all three types of blood cells on its own. You may need ongoing treatment with androgens to control the effects of FA.

Also, over time, androgens lose their ability to help your body make more blood cells, which means you'll need other treatments.

Androgen therapy can have serious side effects, such as liver disease. This treatment also can't prevent you from developing leukemia (a type of blood cancer).

Synthetic Growth Factors

Your doctor may choose to treat your FA with growth factors. These are substances found in your body, but they also can be man-made.

Growth factors help your body make more red and white blood cells. Growth factors that help your body make more platelets still are being studied.

More research is needed on growth factor treatment for FA. Early results suggest that growth factors may have fewer and less serious side effects than androgens.

Gene Therapy

Researchers are looking for ways to replace faulty FA genes with normal, healthy genes. They hope these genes will make proteins that can repair and protect your bone marrow cells. Early results of this therapy hold promise, but more research is needed.

Surgery

FA can cause birth defects that affect the arms, thumbs, hips, legs, and other parts of the body. Doctors may recommend surgery to repair some defects.

For example, your child might be born with a ventricular septal defect—a hole or defect in the wall that separates the lower chambers of the heart. His or her doctor may recommend surgery to close the hole so the heart can work properly.

Children who have FA also may need surgery to correct digestive system problems that can harm their nutrition, growth, and survival.

One of the most common problems is an FA-related birth defect in which the trachea (windpipe), which carries air to the lungs, is connected to the esophagus, which carries food to the stomach.

This can cause serious breathing, swallowing, and eating problems and can lead to lung infections. Surgery is needed to separate the two organs and allow normal eating and breathing.

How Can Fanconi Anemia Be Prevented?

You can't prevent Fanconi anemia (FA) because it's an inherited disease. If a child gets two copies of the same faulty FA gene, he or she will have the disease.

If you're at high risk for FA and are planning to have children, you may want to consider genetic counseling. A counselor can help you understand your risk of having a child who has FA. He or she also can explain the choices that are available to you.

If you're already pregnant, genetic testing can show whether your child has FA. For more information on genetic testing, go to "How Is Fanconi Anemia Diagnosed?"

In the United States, Ashkenazi Jews (Jews of Eastern European descent) are at higher risk for FA than other ethnic groups. For Ashkenazi Jews, it's recommended that prospective parents get tested for FA-related gene mutations before getting pregnant.

Preventing Complications

If you or your child has FA, you can prevent some health problems related to the disorder. Pneumonia, hepatitis, and chicken pox can occur more often and more severely in people who have FA compared with those who don't. Ask your doctor about vaccines for these conditions.

People who have FA also are at higher risk than other people for some cancers. These cancers include leukemia (a type of blood cancer), myelodysplastic syndrome (abnormal levels of all three types of blood cells), and liver cancer. Screening and early detection can help manage these life-threatening diseases.

Living With Fanconi Anemia

Improvements in blood and marrow stem cell transplants have increased the chances of living longer with FA. Also, researchers are studying new and promising treatments for FA. However, the disorder still presents serious challenges to patients and their families.

What To Expect

FA is a life-threatening illness. If you or your child is diagnosed with FA, you and your family members may feel shock, anger, grief, and depression. If you're the parent or grandparent of a child who has FA, you may blame yourself for causing the disease.

Your doctor will want to test all of your children for FA if one of your children is born with the disorder. If you're diagnosed with FA as an adult, your doctor may suggest testing your brothers and sisters for the disorder.

All of these things can create stress and anxiety for your entire family. Family counseling for FA may give you and other relatives important support, comfort, and advice.

One of the hardest issues to deal with is telling children that they have FA and what effect it will have on their lives.

Most FA support groups believe that parents need to give children information about the disorder in terms they can understand. These groups recommend answering questions honestly and directly, stressing the positive developments in treatment and survival.

If your child becomes upset or begins to act out after learning that he or she has FA, you may want to seek counseling.

Special Concerns and Needs

Many people who have FA survive to adulthood. If you have FA, you'll need ongoing medical care. Your blood counts will need to be checked regularly.

Even if you have a blood and marrow stem cell transplant, you remain at risk for many cancers. You'll need to be screened for cancer more often than people who don't have FA.

If FA has left you with a very low platelet count, your doctor may advise you to avoid contact sports and other activities that can lead to injuries.

If your child has FA, he or she may have problems eating or keeping food down. Your doctor may recommend additional, special feedings to support growth and good health.

Support Groups

You or your family members may find it helpful to know about resources that can give you emotional support and helpful information about FA and its treatments.

Your doctor or hospital social worker may have information about counseling and support services. They also may be able to refer you to support groups that offer help with financial planning (treatment for FA can be costly).

Clinical Trials

The National Heart, Lung, and Blood Institute (NHLBI) is strongly committed to supporting research aimed at preventing and treating heart, lung, and blood diseases and conditions and sleep disorders.

Researchers have learned a lot about anemia and other blood diseases and conditions over the years. That knowledge has led to advances in medical knowledge and care.

Many questions remain about blood diseases and conditions, including Fanconi anemia. The NHLBI continues to support research aimed at learning more about these illnesses.

For example, the NHLBI currently is taking part in a research study to examine gene therapy as a treatment for Fanconi anemia.

Much of the NHLBI’s research depends on the willingness of volunteers to take part in clinical trials. Clinical trials test new ways to prevent, diagnose, or treat various diseases and conditions.

For example, new treatments for a disease or condition (such as medicines, medical devices, surgeries, or procedures) are tested in volunteers who have the illness. Testing shows whether a treatment is safe and effective in humans before it is made available for widespread use.

By taking part in a clinical trial, you can gain access to new treatments before they’re widely available. You also will have the support of a team of health care providers, who will likely monitor your health closely. Even if you don’t directly benefit from the results of a clinical trial, the information gathered can help others and add to scientific knowledge.

If you volunteer for a clinical trial, the research will be explained to you in detail. You’ll learn about treatments and tests you may receive, and the benefits and risks they may pose. You’ll also be given a chance to ask questions about the research. This process is called informed consent.

If you agree to take part in the trial, you’ll be asked to sign an informed consent form. This form is not a contract. You have the right to withdraw from a study at any time, for any reason. Also, you have the right to learn about new risks or findings that emerge during the trial.

For more information about clinical trials related to Fanconi anemia, talk with your doctor. You also can visit the following Web sites to learn more about clinical research and to search for clinical trials:

• http://clinicalresearch.nih.gov
• www.clinicaltrials.gov
• www.nhlbi.nih.gov/studies/index.htm
• www.researchmatch.org

For more information about clinical trials for children, visit the NHLBI’s Children and Clinical Studies Web page.

Links to Other Information About Fanconi Anemia

NHLBI Resources

• Anemia (Health Topics)
• Aplastic Anemia (Health Topics)
• Blood and Marrow Stem Cell Transplant (Health Topics)

Non-NHLBI Resources

• Fanconi's Anemia (Medline Plus)
• Inherited Bone Marrow Failure Syndromes (National Cancer Institute)

Clinical Trials

• Children and Clinical Studies
• Clinical Trials (Health Topics)
• Current Research (ClinicalTrials.gov)
• NHLBI Clinical Trials
• NIH Clinical Research Trials and You (National Institutes of Health)
• Patient Recruitment for Studies Conducted by the NHLBI, NIH
• ResearchMatch (funded by the National Institutes of Health)