Fanconi's Anaemia

Fanconi's anaemia, or FA, is a rare, inherited blood disorder that leads to bone marrow failure. FA causes your bone marrow to stop making enough new blood cells for your body to work normally. FA also can cause your bone marrow to make many abnormal blood cells. This can lead to serious health problems such as cancer.

FA is a blood disorder, but it also can affect many of your body's organs, tissues, and systems. Children who inherit FA are at higher risk of being born with birth defects. People with FA are at higher risk for some cancers and other serious health problems.

FA is different from Fanconi syndrome. Fanconi syndrome affects a person's kidneys. It's a rare and serious condition found mostly in children. Children with Fanconi syndrome pass high amounts of key nutrients and chemicals through their urine, which leads to serious health and developmental problems.

Bone Marrow and Your Blood

Bone marrow is the spongy red tissue inside the large bones of your body. Healthy bone marrow makes three types of blood cells:

  • Red blood cells (also called RBCs), which carry oxygen to all parts of your body. They also remove carbon dioxide (a waste product) from your body's cells and carry it to the lungs to be exhaled.
  • White blood cells (also called WBCs), which help your body fight infections.
  • Platelets, which help your blood clot.

Blood cells live for a limited time. Then, they are replaced with new blood cells from your bone marrow. If your bone marrow can't make enough new blood cells to replace the ones that die, you can suffer from serious health problems.

Fanconi Anaemia and Your Body

FA is one of many different types of anaemia. The term "anaemia" is used to describe conditions in which the number of red blood cells in a person's blood is lower than normal.

FA is a type of aplastic anaemia. In aplastic anaemia, the bone marrow slows down or stops making all three types of blood cells. Low levels of the three blood cell types can harm many of the body's organs, tissues, and systems.

With too few red blood cells, your body's tissues won't receive enough oxygen to work well.

With too few white blood cells, your body may have problems fighting infections. This can make you sick more often and make infections worse.

With too few platelets, you may suffer from excessive bleeding.

Outlook

If you or your child has FA, you face a greater risk than other people for some cancers. About 10 percent of people with FA develop leukaemia, a type of blood cancer.

People with FA who survive to be adults are much more likely than others to develop cancerous solid tumors. The risk for solid tumors increases with age in those who have FA. These tumors can develop in your mouth, tongue, throat, or esophagus (the tube leading from your mouth to your stomach). Women who have FA are at much greater risk than women who don't have the disease for developing tumors in the reproductive organs.

FA is an unpredictable disease. The average life span for people who have FA is between 20 and 30 years. The most common causes of death related to FA are bone marrow failure, leukaemia, and solid tumors.

New medical advances have improved the chances of surviving FA. Bone marrow transplant is the major advance in treatment. However, even with a bone marrow transplant, the risk for some cancers is greater in people who have FA.

Other Names for Fanconi Anaemia

  • Fanconi's anaemia

What Causes Fanconi Anaemia?

Fanconi anaemia (FA) is an inherited disease. “Inherited” means that the disease is passed from parents to children through abnormal genes. At least 11 genes can cause FA if they're not normal. FA develops when both parents pass the same abnormal gene for FA to their child.

People who have only one abnormal FA gene are “carriers” of FA. Carriers don't have FA, but they can pass the abnormal gene to their children.

If both of your parents have an abnormal 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 a carrier of FA and passing the gene to any children you have

If only one of your parents has a defective FA gene, you won't develop the disorder. However, there is a 50 percent chance that you will be a carrier and pass the gene to any children you have.

Who Is At Risk for Fanconi Anaemia?

Populations Affected

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

In the United States and Europe, about 1 out of every 300 people is an FA carrier. This carrier rate leads 1 in 360,000 people to be born with FA.

Two ethnic groups—Ashkenazi Jews (Jews of Eastern European descent) and Afrikaners (people native to South Africa)—are more likely than other groups to carry or have FA. In the United States, 1 out of 90 Ashkenazi Jews is a carrier, and 1 out of 30,000 is born with FA. In South Africa, Afrikaners have a carrier rate of 1 in 77, and 1 out of every 22,000 Afrikaners is born with FA.

Major Risk Factors

FA is an inherited disease that occurs when both parents pass an abnormal gene linked to FA to their child.

Children born into families with a history of FA are at risk of inheriting the disease. Children whose mother and father both have family histories of FA are at greater risk. A family history of FA means that it's possible that a parent carries an abnormal gene linked to the disease.

Children whose parents both carry the same abnormal gene are at greatest risk for inheriting FA. These children also are at risk of being carriers of the abnormal gene, even if they aren't born with FA. Children with only one parent who carries the abnormal gene are at risk of being carriers, but they're not at risk of being born with the disease.

What Are the Signs and Symptoms of Fanconi Anaemia?

Major Signs and Symptoms

Your doctor may suspect you or your child has Fanconi anaemia (FA) if there are signs and symptoms of:

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

Because FA is an inherited disease, children may be tested if one of their brothers or sisters has the disease.

Anaemia

If you have anaemia, you have a lower than normal number of healthy red blood cells. This means that your blood isn't able to get enough oxygen to your body's cells, so they can't work normally. Symptoms of anaemia include:

  • Fatigue (tiredness)
  • Weakness
  • Dizziness
  • Coldness in your hands and feet
  • Chest pains
  • Headaches
  • Pale skin

Bone Marrow Failure

When your bone marrow fails, it can't make enough of the three types of blood cells—red and white blood cells and platelets—that your body needs to work normally. This can cause many problems, with various signs and symptoms.

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

With too few white blood cells, you may have infections more often and they may last longer and be more serious than in people who don't have FA.

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 spots caused by bleeding in small blood vessels just below your skin.

Sometimes when you have FA, your bone marrow makes a lot of harmful, immature white blood cells called blasts. These blasts don't work like normal blood cells. As they build up in your bone marrow, they block the production of normal blood cells. A large number of blasts in your bone marrow can lead to a type of blood cancer called acute myeloid leukaemia (AML).

Birth Defects

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

  • Bone or skeleton 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. The spine may be curved—a condition called scoliosis (sco-le-O-sis).
  • Eye and ear defects. The eyes, eyelids, and ears may not be normally shaped. A child also may be born deaf.
  • Skin discolouration. This includes coffee-coloured areas or odd-looking patches of lighter skin.
  • Kidney problems. A child 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). VSD is when the wall that s separates the left and right chambers of the heart (the ventricles) is deformed or has a hole in it.

Developmental Problems

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

  • Low birth weight
  • Poor appetite
  • Slower growth than other children
  • Lower than normal height
  • Small head size
  • Mental retardation or learning disabilities

Signs and Symptoms of Fanconi Anaemia in Adults

Some signs and symptoms of FA may develop as you or your child gets older.

Women with FA may experience some or all of the following:

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

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

How Is Fanconi Anaemia Diagnosed?

People who have Fanconi anaemia (FA) are born with the disease. 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 with the disease 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 history and family history 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 different traits are passed from parents to children through their genes. Geneticists do genetic testing for FA and 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. After your child is born, a paediatrician also can help determine whether your child has FA.

A hematologist—an expert in diagnosing and treating blood conditions—also may help diagnose FA.

Family and Medical History

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 carriers, may not be aware that there is any history of FA in their families. Many parents may not know that FA can be passed from parents to children.

Information on your family's medical history is very important to help your doctor diagnose whether you or your child has FA or another type of condition with similar symptoms.

If your doctor suspects that you, your siblings, or your children have FA, he or she may ask you detailed questions about any personal or family history of anaemia, surgeries related to your digestive system, or diseases of the immune system. Your doctor also may ask you about your appetite, eating habits, and the 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 order further testing.

Diagnostic Tests and Procedures

The signs and symptoms for FA aren't unique to the disease. They're also linked to many other diseases and conditions, such as aplastic anaemia. 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. It shows whether your chromosomes (long chains of genes) break more easily than normal.

Sometimes, skin cells are used for the test, but usually a small amount of blood is taken from a vein in your arm with a needle. A technician combines some of the blood cells that were taken out 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 laboratory to see 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 those 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 as they go through the cycle in this test. This doesn't happen in the cells of people who don't have FA.

Mutation Screening

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

Diagnosing Different Age Groups

Before Birth (Prenatal)

If your family has a history of FA and you become pregnant, your doctor may want to test you or the fetus for FA before birth. Two tests can be used to diagnose FA in a developing fetus. They're done in a doctor's office or hospital.

  • Amniocentesis. This test 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 defective genes linked to FA.
  • Chorionic villous sampling (CVS). This test is done 10 to 12 weeks after a pregnant woman's last period. A doctor inserts a thin tube through the v vagina and cervix to the placenta (the temporary organ that connects the mother to the fetus). He or she removes a tissue sample from the placenta using gentle suction. The tissue sample is sent to a lab to be tested for genetic defects linked to FA. This test doesn't require anesthesia.

At Birth

Three out of 4 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.

Birth defects often linked to FA include:

  • Missing, oddly shaped, or three or more thumbs
  • Poorly developed or missing bones in the arms
  • Hips, legs, hands, and toes that aren't fully or normally formed
  • Curved spine
  • Eyes, eyelids, and ears that aren't fully or normally shaped
  • Skin discolouration
  • Missing or misshapen kidneys
  • Congenital heart defects
  • Mental retardation
  • Serious problems with the digestive system

Childhood and Later

You or your child may be born with FA, but not have birth defects. You may not be diagnosed with the disease until signs of bone marrow failure or cancer begin to show. This normally happens within the first 10 years of life.

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

If your bone marrow is failing, you may show signs of aplastic anaemia. In aplastic anaemia, your bone marrow slows down or stops producing all three types of blood cells: red and white blood cells and platelets. Aplastic anaemia can be acquired after birth through exposure to chemicals, radiation, or medicines; or, it can be inherited, as with FA.

Doctors diagnose aplastic anaemia using:

  • A physical exam and family and medical history.
  • A complete blood count (CBC) to check the number, size, and condition of your red blood cells. The CBC also checks the number of white blood cells and platelets.
  • A reticulocyte count, which counts the number of new red blood cells in your blood to see whether your bone marrow is producing red blood cells at the proper rate.
  • A bone marrow aspiration, in which a small amount of liquid bone marrow is removed and tested to see whether it's making enough blood cells.
  • A bone marrow biopsy, in which 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 anaemia, your doctor will have to determine the cause. If your doctor suspects you have FA, he or she may order genetic testing.

How Is Fanconi Anaemia Treated?

Doctors decide how to treat Fanconi anaemia (FA) based on a patient's age and how well (or how poorly) the patient's bone marrow is producing new blood cells.

Goals of Treatment

Long-term treatments for FA can:

  • Cure the anaemia. 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.

Observation and Short-Term Treatment

If you or your child has FA, but your bone marrow is still able to make many of the new blood cells your body needs, your doctor may perform frequent blood count checks. During this period of observation, your doctor will probably want you to have bone marrow exams once a year. Your doctor also will screen you closely for any signs of cancer or tumors.

If your blood counts begin to drop sharply and stay low, your doctor may assume your bone marrow is failing. He or she may give you antibiotics to help your body fight infections.

In the short term, your doctor 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 chances that other treatments, which can help your body make enough blood cells on its own, will work.

Long-Term Treatment

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

  • Bone marrow transplant
  • Androgen therapy
  • Synthetic growth factors
  • Gene therapy

Bone Marrow Transplant

Bone marrow transplant, also called stem cell transplant, is the current standard treatment for patients with FA that's causing major bone marrow failure. Healthy bone marrow cells from another person, called a donor, are used to replace the abnormal cells in your bone marrow.

Bone marrow transplant is most successful in younger people who have few or no serious health problems, a brother or sister donor, and few or no previous blood transfusions.

Successful bone marrow transplants will allow your body to make enough of all three types of blood cells to work normally. However, if you've had a transplant to treat FA, you will still be at risk for some types of blood cancer and for developing cancerous solid tumors. Your doctor will check your health regularly and often after the procedure.

Finding a donor. A key factor for bone marrow transplant success is finding a donor whose bone marrow cells your body won't reject. Your body is more likely to accept cells that can work with your own cells without causing unhealthy side effects. If the new cells don't match, your body's immune system may attack and destroy them. This is similar to how the body responds when it's invaded by something from the outside, like a virus or bacteria.

To determine whether a donor's cells will work with yours, your doctor will use a blood test called HLA typing. This test looks at proteins on the surface of blood cells. The proteins are called human leukocyte antigens (HLA). Your blood and the donor's blood are tested, and the HLA antigens on the blood cells are compared. If your HLA is similar to the donor's, it means your body is less likely to try to fight and destroy the donor's cells.

The greatest chance (up to 80 percent) for a successful bone marrow transplant generally is if your brother or sister donates bone marrow and if you and your sibling have matching HLA.

It's possible to have a successful bone marrow transplant from a donor who isn't related to you, but success rates for this type of transplant are less than 50 percent. It's also possible to have a successful transplant using cells from umbilical cord blood. Because these types of transplants are riskier, doctors only use cells from nonrelated donors for transplants:

  • If you have cancer (leukaemia or myelodysplastic syndrome)
  • If you have no HLA-matched brother or sister to donate cells
  • If your body can't tolerate other treatments for bone marrow failure

Receiving the transplant. Bone marrow transplants are done in special units in hospitals to try to protect the person receiving the transplant from infections. Before the transplant, you receive high doses of chemotherapy, radiation therapy, or both. These treatments destroy the abnormal bone marrow that isn't producing blood cells.

A sample of bone marrow is taken from the donor and given to you through a vein. The donated bone marrow cells travel to your bone marrow and start to make healthy blood cells. If the transplant is successful, the new bone marrow cells multiply and begin making new, healthy blood cells within 3 to 4 weeks.

Possible complications. After a bone marrow transplant, you may be in the hospital for weeks or months. During this time, you're isolated and closely watched for infections and other complications. Complications are most likely to occur in the first 100 days after a transplant.

Complications after bone marrow transplant include:

  • Rejection of the new cells
  • A condition called graft rejection
  • A condition called graft-versus-host disease (GVHD)

Graft rejection occurs when your immune system destroys the new bone marrow cells. This occurs in 5 to 10 percent of people who get bone marrow transplants. It's more likely to happen in people who have had several transplants.

GVHD happens when the new white blood cells, created by the donated bone marrow cells, attack your body. Signs and symptoms include skin inflammation, severe diarrhoea, and liver disease. GVHD can occur soon after transplant, or it can develop slowly and can last for months or years. GVHD most often happens in older people and those who receive unmatched transplants.

To help prevent GVHD, the donor marrow is sometimes treated, or you may get medicines that suppress the immune system after the transplant. Sometimes symptoms of GVHD are treated with medicines such as steroids.

Androgen Therapy

Before improvements made bone marrow transplants more effective, androgen therapy was the standard treatment for people with FA. Androgens are artificial male hormones that can help your body make more blood cells for long periods.

Androgens are effective in increasing your red blood cell count. They also help to increase your platelet count. They're less effective in making more white blood cells in your body.

Unlike bone marrow transplant, androgens don't enable your bone marrow to produce 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, androgens eventually lose their ability to help your body make more blood cells, which means you will need other treatments.

Androgen treatment can have serious side effects, such as liver disease, and it can't prevent you from developing leukaemia.

Synthetic Growth Factors

Your doctor may choose to treat your FA with substances known as growth factors. These are substances found in your body, but they also can be man-made. They help your body make more red and white blood cells. Growth factors that can help your body make more platelets are still being researched. One of the more common growth factors used to treat FA is called EPO, or erythropoietin (e-RITH-ro-PO-e-tin).

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 abnormal FA genes with normal, healthy genes. They believe that the replacement genes will be able to make the proteins needed to repair and protect your bone marrow cells.

Gene therapy uses viruses that have been altered so that they can deliver normal genes to replace abnormal ones in FA patients' bone marrow stem cells.

Early results hold promise, but this form of treatment for FA is still in the experimental stage.

Surgery

Surgery may be needed to improve the use of arms, thumbs, hips, legs, and other parts of the body that are malformed or underdeveloped due to birth defects caused by FA.

If your child is born with a heart defect linked to FA called ventricular septal defect, he or she may need surgery to close the hole in the heart's wall so the heart can function normally.

Children with FA also may need surgery to correct problems in the digestive system that can harm their nutrition, growth, and survival. One of the most common problems is an FA-related birth defect where the windpipe (trachea), 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 to allow normal eating and breathing.

How Can Fanconi Anaemia Be Prevented?

Fanconi anaemia (FA) is an inherited disease and can't be prevented. If a child receives the same defective genes linked to FA from both parents, he or she will have the disease.

You can prevent certain complications linked to FA. Pneumonia, hepatitis, and chicken pox can occur more often and more severely in people with FA. Make sure you or your child is vaccinated for these diseases.

If you or your child has FA, you're more likely to develop certain cancers than people who don't have FA. These include leukaemia (a type of blood cancer), myelodysplastic syndrome (abnormal levels of all three types of blood cells), and liver cancer. Screening and early detection are important to manage these life-threatening diseases.

Living With Fanconi Anaemia

If you or your child has Fanconi anaemia (FA), your chances for survival have increased due to improvements in bone marrow transplantation. In addition, other new treatments are being developed that hold promise. But FA still presents serious challenges to patients and their families.

What To Expect

FA is a life-threatening illness. This is an emotionally difficult issue for people with FA and their families. If you or your child is diagnosed with FA, you and your family members may experience shock, anger, grief, and depression. If you're the parent or grandparent of a child with FA, you may blame yourself for causing the disease.

Your doctor will want all of your children tested for FA if one of your children is born with the disease. If you're diagnosed with FA as an adult, your doctor will recommend that your brothers and sisters be tested for the disease.

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 that will help you deal with the problems FA can cause.

One of the most difficult 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 disease in terms they can understand. These groups recommend that questions be answered honestly and directly, stressing the positive developments in treatment and survival.

If your child becomes upset or begins to develop behavioral issues after learning that he or she has FA, you may want to seek counseling from a therapist.

Special Concerns and Needs

Many people with FA live into adulthood. If you have FA, you will require regular and ongoing medical attention. Your blood counts will need to be monitored regularly. Although your body can use healthy bone marrow cells from a donor to make the blood cells you need, you remain at risk for many cancers. You will need to be screened for FA-related cancers more often than people who don't have FA.

If FA has left you with very low levels of platelets in your blood, your doctor may advise you to avoid contact sports and other activities that carry the risk of physical injury.

If your child has FA, he or she may have problems eating or keeping food down. Your doctor may recommend additional special feedings to keep your child's weight at a level needed for ongoing development and good health.

Key Points

  • Fanconi anaemia (FA) is a rare, inherited blood disorder that leads to bone marrow failure.
  • FA causes your bone marrow to stop making enough new blood cells for your body to work normally. It also can cause your bone marrow to make many abnormal blood cells.
  • Although FA is a blood disease, it can affect many of your body's organs, tissues, and systems. People with FA are at higher risk for certain cancers, birth defects, and other serious health problems.
  • FA is a type of aplastic anaemia. In aplastic anaemia, your bone marrow slows down or stops making all three types of blood cells: red and white blood cells and platelets.
  • FA is an inherited disease. It's passed from parents to children through their genes. If a child receives the same defective gene linked to FA from both parents, the child will have FA.
  • FA occurs in all racial and ethnic groups and affects men and women equally. Two ethnic groups—Ashkenazi Jews and Afrikaners—are more likely than other groups to have FA.
  • Signs and symptoms of FA often are present at birth in the form of birth defects. Children born with FA, but without birth defects, tend to develop symptoms early. These include fatigue (tiredness) caused by anaemia, illnesses linked to bone marrow failure, and physical and mental development problems.
  • Family history is important for diagnosing FA. A diagnosis of FA is confirmed through genetic tests, including chromosome breakage testing, cytometric flow analysis, and mutation screening.
  • Bone marrow transplant is the most effective treatment for FA, especially if the donor is a brother or sister with matching bone marrow cells. Other treatments include androgen therapy and synthetic growth factors that increase blood counts, but can't reverse bone marrow failure.
  • Children with FA may need surgery to improve the use of thumbs, arms, hips, legs, and other parts of the body that are malformed or underdeveloped due to birth defects caused by the disease. Surgery also may be needed to correct heart defects or problems in the digestive and breathing systems.
  • FA is an unpredictable disease. The most common causes of death in people who have FA are bone marrow failure, leukaemia (a type of blood cancer), and cancerous solid tumors. The average life expectancy for people with FA is between 20 and 30 years.
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