Fanconi anemia

As of June 1, 2016, mutations or abnormalities in 19 genes have been determined to cause Fanconi anemia. These 19 genes include: FANCA, -B, -C, -D1 (also known as BRCA2), -D2,- E,- F, -G, -I,- J (also known as BRIP1),- L, -M, -N, -O, -P, -Q, RAD51, BRCA1, and –T. Proteins made from genes are involved in the FA pathway, which helps with repairing damaged DNA (or genetic material) during DNA replication (the process by which new copies of DNA are made). The FA pathway responds to a specific type of DNA damage called interstrand cross-links (ICLs), in which the two opposite strands of DNA are abnormally fused. ICLs stop the process of DNA replication. Without a properly functioning FA pathway, cells die and DNA damage builds up, which leads to features seen in Fanconi anemia.

Who else in the family should be tested for Fanconi anemia (FA) depends on the inheritance pattern of the specific genetic change that is causing FA in the family. For example, FA is usually caused by genes inherited in an autosomal recessive manner (except for cases caused by FANCB). If an affected person’s FA is caused by an autosomal recessive gene, siblings of the affected person might consider testing for FA. If an affected person’s FA is caused by FANCB, the person’s mother should first be tested to see if she is a carrier for a FANCB mutation to determine the risk for other family members. Genetic counselors are available to discuss who else in your family should be tested for FA. To find genetic counselors in your area, please refer to www.nsgc.org and click "find a genetic counselor".

A list of labs that perform testing for Fanconi anemia (FA) is available in the Fanconi Anemia Research Fund, Inc. . International Fanconi Anemia Treatment and Testing Resource Guide: http://fanconi.org/images/uploads/other/2015_Resource_Guide.pdf and on www.nextgxdx.com.

Some websites with reliable information on Fanconi anemia include:

No one can predict how long any person will with Fanconi anemia (FA) will survive. Each person with FA is unique and might present with different symptoms or the condition. Accoring to cases reported by the Internation Fanconi Anemia Registry, the average life expectancy for people with FA is about 20 to 30 years. Some patients live into their 30’s, 40’s, and 50’s. It is important to note that anyone can have a different life expectancy than any “average”. New research in FA has improved treatments, which can extend one’s life expectancy.

Individuals with Fanconi anemia (FA) might see a geneticist and/or a genetic counselor for genetic testing for FA and to discuss how the condition is passed on from parents to children. People with FA may also see a hematologist (blood disease doctor), cardiologist (heart doctor), ophthalmologist (eye disease doctor), neurologist (brain and spinal cord doctor), and an oncologist (doctor who treats cancer) depending on what features of the condition they have.

The usual abbreviation for Fanconi anemia is FA.

Hematopoietic stem cell transplantation (HSCT) is a treatment for people with Fanconi anemia who are experiencing major bone marrow failure. This involves getting donated stem cells in a procedure like a blood transfusion. If HSCT is successful, your body can begin making enough blood cells.

Hematopoietic growth factor therapy for Fanconi anemia involves treatment with growth factors that can help your body make more red and white blood cells.

Fanconi anemia (FA) is a genetic condition that can lead to anemia (low red blood cell count), bone marrow failure, physical abnormalities, defects in different body organs, and an increased risk for cancer. It is estimated that about 60-75% of people with FA have physical abnormalities, which include unusually light colored skin (hypopigmentation) or café au lait spots (dark patches of skin). People with FA may also have abnormalities with their skeletal system, kidneys, gastrointestinal system, heart, eyes, ears, genitalia, reproductive system, brain, and spinal cord. FA also causes an increased risk for a type of cancer called acute myeloid leukemia (AML), as well as other tumors of the head, neck, skin, gastrointestinal system, or genital tract. Current therapies and treatments for FA include: stem cell transplant, blood transfusions, androgen therapy, and surgery for birth defects.

Androgen therapy for Fanconi anemia involves taking hormones called androgens, which helps improve blood counts in about 50% of people with Fanconi anemia.

For individuals with Fanconi anemia (FA), doctors should monitor blood counts and for signs of bone marrow failure. Doctors should also watch for signs of blood cancers and other solid tumors of the head and neck, skin, esophagus, and gynecologic areas.

As of June 1, 2016, mutations or abnormalities in 19 genes have been determined to cause Fanconi anemia. These 19 genes include: FANCA, -B, -C, -D1 (also known as BRCA2), -D2,- E,- F, -G, -I,- J (also known as BRIP1),- L, -M, -N, -O, -P, -Q, RAD51, BRCA1, and –T. Proteins made from genes are involved in the FA pathway, which helps with repairing damaged DNA (or genetic material) during DNA replication (the process by which new copies of DNA are made).

The main symptoms of Fanconi anemia include: aplastic anemia, bone marrow failure, birth defects (including unusually light colored skin (hypopigmentation) or café au lait spots (dark patches of skin), abnormalities with their skeletal system (particularly short stature, abnormal thumb and radius), kidneys, gastrointestinal system, heart, eyes, ears, genitalia, reproductive system, brain, and spinal cord), developmental delays, and an increased risk for cancer.

Kidney abnormalities that can be seen with Fanconi anemia include:

Heart defects that are associated with Fanconi anemia include:

Gastrointestinal abnormalities that can be seen with Fanconi anemia include:

Eye abnormalities that can be seen with Fanconi anemia (FA) include abnormally small eyes, cataracts (clouding of the lens of the eye), astigmatism (differences in the eye’s curvature), strabismus (differences in the alignment of the eyes), hypertelorism (widely-spaced eyes), hypotelorism (closely spaced eyes), epicanthal folds (skin folding of the upper eyelid), ptosis (droopy upper eyelid).

If your child has Fanconi anemia caused by PALB2, you are likely a carrier for a PALB21 mutation and should consider genetic testing. Individuals with a PALB2 mutation are at increased risk for breast and pancreatic cancer. Genetic counselors are available to discuss and coordinate testing for BRIP1. To find genetic counselors in your area, please refer to www.nsgc.org and click "find a genetic counselor".

If your child has Fanconi anemia caused by BRIP1, you are likely a carrier for a BRIP1 mutation and should consider genetic testing. Individuals with a BRIP1 mutation are at increased risk for breast and ovarian cancer. Genetic counselors are available to discuss and coordinate testing for BRIP1. To find genetic counselors in your area, please refer to www.nsgc.org and click "find a genetic counselor".

If your child has Fanconi anemia caused by BRCA2, you are likely a carrier for a BRCA2 mutation and should consider genetic testing. Individuals with a BRCA2 mutation are at increased risk for breast, ovarian, as well as other cancers. Genetic counselors are available to discuss and coordinate testing for BRCA2. To find genetic counselors in your area, please refer to www.nsgc.org and click "find a genetic counselor".

No, there is no routine newborn testing for Fanconi anemia.

As of June 10th, 2016, the following government sponsored trials (specifically for Fanconi anemia) are recruiting participants (based on clinicaltrials.gov). Note that there may be other studies on clinicaltrials.gov that recruiting patients with Fanconi anemia along with patients with other conditions. The Fanconi Anemia Research Fund, Inc. website is also a good resource for research studies on Fanconi anemia.

Quercetin in Children With Fanconi Anemia; a Pilot Study
Sponsor: Children’s Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT01720147

Hematopoietic Stem Cell Transplantation in High Risk Patients With Fanconi Anemia
Sponsor: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT00258427

Pilot Study Assessing the Feasibility of CD34+ Cells Mobilization and Collection After Treatment With G-CSF and Plerixafor in Patients With Fanconi Anemia for Subsequent Treatment by Gene Therapy
Sponsor: Assistance Publique – Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT02678533

A Study of Cyclophosphamide, Fludarabine, and Antithymocyte Globulin Followed by Matched Sibling Donor Hematopoietic Cell Transplantation in Patients With Fanconi Anemia
Sponsor: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov IdentifierNCT00630253

Gene Transfer for Patients With Fanconi Anemia Complementation Group A (FANCA)
Sponsor: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT01331018

A Phase II Trial of HSCT for the Treatment of Patients With Fanconi Anemia Lacking a Genotypically Identical Donor, Using a Risk-Adjusted Chemotherapy Only Cytoreduction With Busulfan, Cyclophosphamide and Fludarabine
Sponsor: Children’s Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT02143830

Total Body Irradiation Dose De-escalation Study in Patients With Fanconi Anemia Undergoing Alternate Donor Hematopoietic Cell Transplantation
Sponsor: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT00352976

Microcephaly Genetic Deficiency in Neural Progenitors: Genotyping, Phenotyping and Functional Neuro-anatomy and Neurobiology Comparative Primitive Microcephaly (MCPH) and the Fanconi Anemia (FA)
Sponsor: Assistance Publique – Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01565005

There is more than one test to diagnose Fanconi anemia (FA). The first step in testing for FA is usually a blood test called a chromosome breakage study with diepoxybutane (DEB) and mitomycin C (MMC). If this test is negative and FA is still suspected, the same test can be repeated on skin cells. Once a diagnosis is confirmed through chromosome breakage studies, tests called complementation analysis or gene sequencing can be performed to determine which specific genes are responsible for causing FA.

People with Fanconia anemia (FA) are sensitive to chemo and radiotherapy and should discuss risks associated with these treatments with their doctors. Radiographic studies should be minimized, since people with FA are sensitive to radiation. People with FA should also avoid environmental exposures that are known to cause tumor growth including smoking, second-hand smoke, and alcohol.

The current standard treatment for individuals with Fanconi anemia (FA) who are experiencing bone marrow failure is blood and bone marrow stem cell transplant, where healthy stem cells from another person (also called a donor) are used to replaced cells that are not working properly in the bone marrow. Other treatments for FA include androgen therapy, which can improve blood counts in about half (50%) of patients with FA, and treatment with growth factors, which can improve white blood cell counts in some. It is important to note that these above mentioned treatments do not prevent affected individuals from developing blood cancers or other solid tumors.

Prenatal diagnosis is available for Fanconi anemia. Prenatal genetic counselors are available to discuss different prenatal diagnosis options with you. To find genetic counselors in your area, please refer to www.nsgc.org and click "find a genetic counselor".

Preconception genetic diagnosis (PGD) is available for Fanconi anemia (FA) if the gene alteration causing FA in the family has been identified.

Gene therapy is currently not a standard treatment for Fanconi anemia (FA). There is still ongoing research on the efficacy of this technology for FA.

If you have Fanconi anemia (FA), it is likely that you will show symptoms of the condition. However, not everyone with FA presents with all symptoms related to this condition. For example, it is estimated that about 60-75% have physical abnormalities including bone or skeletal differences, eye and ear defects, skin pigmentation differences, kidney problems, and congenital heart defects. 10-30% will develop blood cancers, and 25-30% will develop other solid tumors. By about 40-50 years old, about 90% of people with FA will have bone marrow failure.

People with Fanconi anemia (FA) are at an increased risk for developing blood cancers as well as other solid tumors. However, not everyone with FA will get cancer.

People with Fanconi anemia (FA) are at an increased risk for a type of cancer called acute myeloid leukemia (AML), as well as other tumors of the head, neck, skin, gastrointestinal system, or genital tract.

If you have Fanconi anemia (FA), your doctor should work closely with other specialists to manage your care. For example, a geneticist and/or genetic counselor can assist with genetic testing for FA and discuss how the condition is passed on from parents to children. You doctor may also work with other specialists including a hematologist (blood disease doctor), cardiologist (heart doctor), ophthalmologist (eye disease doctor), neurologist (brain and spinal cord doctor), and an oncologist (doctor who treats cancer) depending on what features of the condition you have.

There are some risks associated with pregnant if you have Fanconi anemia (FA). There are some reports of women’s FA symptoms becoming worse after becoming pregnant. It is important to discuss the risks associated with becoming pregnant with your doctor.

People with Fanconi anemia (FA) may have difficulties becoming pregnant, but it is possible to become pregnant.

If you have Fanconi Anemia and are pregnant, you might consult a maternal fetal medicine specialist (doctors who manage high-risk pregnancies), a geneticist and/or genetic counselor (to discuss how this condition may be passed on to your children), and a hematologist (to monitor your anemia and blood counts). It may be necessary for you to consult other specialists and you should talk to your doctor about which specialists you should see during your pregnancy.

It is estimated that about 1 in every 131,000 children in the U.S. are born with Fanconi anemia.

Fanconi anemia (FA) is inherited in an autosomal recessive manner except in cases where it is caused by mutations or abnormalities in the FANCB gene.

For cases of FA caused by mutations in FANCA, -C, -D1 (also known as BRCA2), -D2,- E,- F, -G, -I,- J (also known as BRIP1),- L, -M, -N, -O, -P, -Q, RAD51, BRCA1, and –T, FA is inherited in an autosomal recessive manner. Everyone (including people without FA) has two copies of each of these FA genes. For example, everyone has two copies of the FANCA gene. When someone has a mutation in one copy of the FANCA gene, they are called carriers. Carriers do not typically show signs of FA. When a male and a female carrier of a FANCA mutation have children together, they have a 1 out of 4 (or 25%) chance of passing on both copies of FANCA with a mutation to each child. A child is affected with Fanconi anemia if they inherit both copies of FANCA with a mutation from his/her parents.

For cases of FA caused by mutations in the FANCB gene, FA is inherited in an X-linked manner. Patients with FA caused by a FANCB mutation are all male. The father of a male with a FANCB FA will not have FA nor will he be a carrier of the FANCB mutation. The mother of the affected male may be a carrier of the FANCB mutation or the mutation may be unique (also known as de novo) in the affected male. In de novo cases, the mother is not a carrier.

Genetic counselors are available to discuss inheritance of FA. To find genetic counselors in your area, please refer to www.nsgc.org and click “find a genetic counselor”.

To give money to help with Fanconi anemia reseach. Please visit the Fanconi Anemia Research Fund, Inc. website: http://fanconi.org/index.php/donate

To get tested for Fanconi anemia (FA) contact your local medical geneticist and/or genetic counselor. A medical geneticist will typically perform a genetics evaluation, which may include a physical exam and blood tests to look for signs of FA. A blood test called a chromosome breakage study is used to confirm a diagnosis of FA.

To find clinical research in Fanconi anemia (FA), please go to: clinicaltrials.gov. Under “Search for Studies”, enter “Fanconi Anemia”. A list of government funded studies on Fanconi anemia will appear.

To find an expert or team experienced in taking care of people with Fanconi anemia, please refer to the Fanconi Anemia Research Fund, Inc. International Fanconi Anemia Treatment and Testing Resource Guide: http://fanconi.org/images/uploads/other/2015_Resource_Guide.pdf

People with Fanconi anemia should avoid smoking, second-hand smoke, and alcohol. Radiographic studies should also be minimized. Talk to your doctor about other things that you should avoid if you have Fanconi anemia.

Stem cell transplantation is not successful for everyone with Fanconi anemia. Stem cell transplants are usually most successful in people who are younger and who:

There are side effects of androgen therapy. Side effects of androgen therapy for Fanconi anemia can include liver disease. Androgen therapy also does not preclude people with FA from developing leukemia.

Fanconi anemia might also be called Fanconi pancytopenia.

Blood and marrow stem cell transplant, androgen therapy, and growth factor treatment are used to treat patients with Fanconi anemia (FA) experiencing bone marrow failure. FA can also cause birth defects of the arms, thumbs, hips, legs, and other parts of the body and doctors may recommend surgery depending on the birth defect.

Fanconi anemia (FA) should be suspected for anyone born with thumb or arm abnormalities and anyone developing aplastic anemia (a condition in which the bone marrow does not make enough blood cells) at any age.

The Fanconi Anemia Research Fund, Inc. is a great support group for people and families affected by Fanconi anemia.

Other conditions that may show increased chromosome breakage like Fanconi anemia (FA) include: Bloom syndrome, ataxia-telangiectasia, Nijmegen breakage syndrome (NBS), and Seckel syndrome.

People with neurofibromatosis 1 (NF1) also have café au lait spots or dark patches of skin like individuals with FA.

Finally, people with TAR syndrome (thrombocytopenia with absent radii), and non-FA-related VACTERL association may also show similar skeletal differences as FA.