Fanconi Anaemia in Children-Symptoms, Diagnosis, and Prevention by Dr. Stalin Ramprakash

Fanconi anaemia results in different types of head and neck cancers, and blood cancers like myelodysplasia which is the early form of leukaemia and leukaemia. Children suffering from Fanconi anaemia are most vulnerable to a type of cancer called Acute Myeloid Leukemia. Fanconi anaemia is a rare genetic disorder and the tendency to develop Fanconi anaemia runs in families.

Causes of Fanconi Anaemia in Children

Inherited gene mutations cause Fanconi anaemia in children. It can be X-linked recessive inheritance where the genetic mutations will be on the X chromosome or autosomal recessive inheritance. X-linked inheritance is mostly passed on by a mother to the child as the mother will have two X chromosomes (one defective and another normal gene).

Autosomal Fanconi anaemia, which is far more common, is of recessive inheritance, where both the parents may have one defective and one normal gene. Parents may not have the disease, but they can pass on the condition to the future generation and are called carriers of the mutated gene.

These genes play a vital role in producing certain proteins that repair a particular type of DNA damage called Interstrand Crosslinks (ICLs). ICLs form due to the wrong linkage between the DNA strands. These ICLs stop the DNA from replicating further and prevent the expression of genes. When such toxic DNA damage occurs, a pathway called FA (Fanconi Anemia) pathway helps in repairing the damaged DNA thus helping the DNA to replicate further and helping genes to work properly.

In Fanconi anaemia the genes which are responsible for the repair of DNA damage are defective thereby allowing progressive accumulation of DNA, damage that eventually leads to bone marrow failure and a predisposition to cancer. There are at least 17 known mutated genes that can cause Fanconi anaemia in children.

In addition to inherent predisposition to solid cancers in the head and neck and genital region, bone marrow failure can progress to other blood-related cancers such as myelodysplastic syndrome and acute myeloid leukaemia.

Which Child is at Risk of Fanconi Anaemia?

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Children with a family history of such abnormal gene mutations are at a high risk of inheriting the disease. Parents, in such cases, remain carriers and will not have the disease. Children who inherit the disease can have many physical abnormalities.

It is important to note that up to 30 % of affected individuals may not show any external physical abnormalities and the first clinical sign of the disease may be the onset of bone marrow failure.

Fanconi anaemia is a rare genetic disorder that comes with physical abnormalities leading to bone marrow failure and other cancers. Children with Fanconi Anemia may have to be under lifelong medical monitoring.

Symptoms of Fanconi Anaemia in Children

Children with Fanconi Anemia are born with physical abnormalities like

• Short stature is one of the symptoms that indicate Fanconi anaemia. It is a congenital defect that may be because of the deficiency in growth hormones in children born with Fanconi anaemia and other hormonal and non-hormonal causes.
• Small head and small eyes.
• Missing fingers or unusual y short fingers, thumb deformities, extra fingers, double thumb, thumb with three segments, shorter forearms, poor development of the radial bone of forearm and other bone deformities.
• Kidney and heart problems.
• Ear abnormalities and Gastrointestinal abnormalities, such as an abnormal connection between trachea and oesophagus, failure to develop anal opening etc.
• Genital abnormalities
• Hip and spine skeletal structure abnormalities.
• Abnormal skin pigmentation (hyper or hyperpigmentation).
• Growth deficiency and decreased learning abilities.

Children with Fanconi anaemia might also have other endocrine abnormalities along with growth hormone deficiency. Children with both problems are observed to be shorter in stature than children with only growth hormone deficiency. Endocrine abnormalities lead to thyroid problems, insulin abnormalities, and obesity.

A congenital heart defect is a heart problem that comes with birth. Children with only congenital heart defects may not necessarily have Fanconi anaemia.

Children with Fanconi anaemia may have none or some abnormalities. The above-described congenital abnormalities in isolation or in combination with other genetic medical conditions as well.

Can Children With Fanconi Anaemia Have Aplastic Anaemia?

Children born with Fanconi anaemia may also encounter aplastic anaemia. The symptoms of aplastic anaemia in children are.

• Unusual bleeding and bruising, nosebleeds, and bleeding from the gums occur due to the inability of blood platelets to clot the blood at the place of injury.
• Inadequate numbers of white blood cells can cause recurring or long-term infections.
• Breathing issues and reduced ability for exercise and sports. This is due to the reduced erythrocytes or red blood cells.
• Tiredness and pale skin.

[Read : Aplastic Anaemia in Children]

Diagnosis of Fanconi Anaemia in Children

Doctors will take the child through multiple steps before finalising the diagnosis. Here are some of the standard tests for diagnosing the condition.

1. Medical History

To diagnose Fanconi Anemia in children, the doctors will start with medical history. Your doctor will go through the symptoms, current difficulties, past history and family history.

2. Physical Examination

A physical examination will be done to look for any congenital abnormalities and clinical signs of Fanconi anemia. A gold standard test is a type of test which is considered the most reliable one based on the medical conditions of the patient.

3. Chromosomal Breakage Test

In children with Fanconi anaemia, the chromosomal breakage test is considered the gold standard test. Doctors may recommend this if they observe signs and symptoms related to Fanconi anaemia.

4.Blood Tests

Blood tests to determine the number of Red Blood Cells, White Blood Cells, and platelets. A haematologist will carry on all the blood tests and the whole blood-related work and examination. The doctor may also request for tests to determine the thyroid, lipid profile, and iron content in the blood may be requested.

5. X-Rays

Doctors may also suggest X-Ray tests to check for any structural anomalies in children with Fanconi anaemia.

6. Bone Marrow Biopsy

If there are features of aplastic anaemia or poor marrow function, doctors will perform a test called bone marrow aspiration and biopsy to assess the severity. The bone marrow is a soft and spongy tissue inside the bones with stem cells in it. Healthy stem cells produce normal and functioning red, white blood cells and blood platelets. If the stem cells are affected, the bone marrow will not be able to contribute healthy cells to the body. Bone marrow biopsy is an important medical procedure that can analyze all the above functions of the bone marrow.

7. Ultrasounds

Ultrasound of the kidneys and liver will help identify for any anomalies.

Fanconi anaemia will not always be symptomatic. It is important to check for any physical abnormalities like short fingers and forearms in infants. This can help doctors to diagnose the disease in the early stages and select the treatment options accordingly.

Treatment of Fanconi Anaemia in Kids

Children with Fanconi anemia need close monitoring by parents and doctors. Treatment options are always based on the child’s clinical status and pathology reports. Some children may not have any symptoms related to Fanconi anemia till a certain age. Even if the child does not have any symptoms the child needs to be followed up regularly to detect the development of bone marrow failure early and needs to have regular cancer surveillance to detect the development of malignancy early. Treatment will depend on any pre-existing physical abnormalities and any new complications that develop over time.

Some of the treatments for Fanconi anaemia are

1. Growth Factors

Growth factors increase the production of white blood cells in children suffering from bone marrow failure due to Fanconi anemia.

2. Androgen Therapy

Children with Fanconi anaemia suffer from bone marrow failure where the blood count drops and decreases leading to other health complications. In such cases, androgen therapy can substantially increase the blood count. Unfortunately, the treatment is effective only in half of the patients and is more likely to work in moderate than severe aplastic anaemia. This can help the body acquire healthy blood cells to carry on with its functions. They are not permanent cures but prolong the life of the patient.

3. Cancer Treatments

Fanconi anaemia in children leads to certain types of head, neck, and reproductive organ cancers at an early age around 15 – 35 years of age. Children with cancers may require surgery, chemotherapy and radiotherapy depending on the nature and location of the cancer.

4. Blood Transfusions

For low blood counts, red blood cell transfusions and blood platelet transfusions are very much needed for the children suffering from bone marrow failure because of Fanconi anaemia. Blood transfusions are carried out under safe conditions with an IV inserted into the child’s vein. It is very much necessary to monitor the changes in children who undergo blood transfusions. Children may also suffer from side effects because of blood transfusions.

5. Bone Marrow Transplant

Bone marrow transplantation is a process in which defective bone marrow of the affected child is removed is replaced with healthy bone marrow from the donor. This can help in the increased production of healthy blood cells and may permanently cure bone marrow failure. Doctors would prefer a fully matched sibling as the donor. Doctors will select the donor from the child’s close family members if available. They will take extreme care during the bone marrow transplants for the children with Fanconi anaemia as bone marrow transplant is a life-saving procedure. Recently increasing success is noted with unrelated and half-matched related donor transplants with modern transplant procedures.

[Read : Bone Marrow Transplant For Children]

6. Gene Therapy

Gene therapy is a new and ongoing research treatment option to increase hematopoietic stem cells or HSCs in children suffering from Fanconi anaemia. This can help in the increased production of blood cells by managing bone marrow failure.

7. Surgery

Surgery may be a requirement to correct the deformed body parts in children suffering from Fanconi anaemia.

Complications of Fanconi Anaemia in Kids

Children suffering from Fanconi anaemia face several complications like

1. Bone Marrow Failure And Anaemia

Bone marrow failure leads to pancytopenia which is the deficiency of three types of blood cells (red blood cells, white blood cells, and thrombocytes or blood platelets). It may start with any one of the cell lines and progress to affect all three cell lines.

2. Growth deficiency

Children with Fanconi anaemia may suffer poor growth due to many factors including have a growth hormone deficiency, other hormonal deficiencies, and skeletal abnormalities.

3. High Risk of Neck And Head Cancers

As we discussed earlier, kids with Fanconi anaemia have a higher predisposition for neck and head cancers. The defects in the DNA cause an uncontrollable growth of cells leading to cancer.

4. Acute Myeloid Leukaemia And Myelodysplasia

Children with Fanconi anaemia suffer from bone marrow failure. Bone marrow failure involves a high risk of progressing to myelodysplasia (an early form of leukemia) and acute myeloid leukemia. Children with Fanconi anaemia are at an increased risk of getting solid head and neck tumours.

[Read : Leukaemia in Children]

5. Kidney And Heart Problems

Organ defects are one of the complications that come along with Fanconi anaemia. Children born with Fanconi anaemia may have congenital heart and kidney problems.

How to Help Your Child Deal With Fanconi Anaemia?

Children with Fanconi anemia need lifelong monitoring and treatment.

• Regular consultations with your child’s doctor and changing the medication according to their condition can help avoid serious health complications.
• Regular screening for cancers will increase your child’s chance of successfully fighting and overcoming cancer.
• Early detection can also provide better and more promising treatment options with higher chances of cure.
• Indulge yourself and your child in engaging activities, so that your child can stay active and sharpen their learning abilities.
• Regular blood tests are helpful to identify and deal with any blood-related complications that follow bone marrow failure.
• Discuss with your child’s doctor regarding the medication. It is important to make sure your child is leading a quality life.

When to Consult a Doctor?

Children born with Fanconi anaemia majorly show physical abnormalities. Some children are born without any defects but can eventually develop the symptoms at an early age.

You must consult your doctor in the following situations

• If you observe any forearm or body structural related abnormalities in your child during their growth.
• Irregular skin color like hyper or hypopigmentation.
• Symptoms in children with bone marrow defect such as increased tiredness or breathing problems because of insufficient oxygen supply to the body, bleeding and bruising frequent, severe and long-term infections.

Children born with Fanconi anaemia fall at risk of encountering cancers. Regular screening and early detection can help them improve their quality of life.

How to Prevent Another Child From Being Born With Fanconi Anaemia?

Genetic disorders like Fanconi anaemia are preventable but not curable. Here is what you can do to prevent your next child from inheriting this condition.

1. Genetic Testing

A genetic test can be very much useful to analyze if the disease runs in the family. Before having a child, a genetic screening test is necessary for those who are aware of their family history. This can help them prevent the child from inheriting the mutated gene with proper counselling and medical procedures.

2. Genetic Counselling

It is also important to get genetic counselling by discussing the family history with your doctor. The doctor may look at the family history and the possibility of the couple passing the mutated gene to their child. It can help in understanding the prevention methods and the predispositions that can be handled even if the child is born with such a condition.

3. Antenatal Testing

Early antenatal screening and chorionic villus biopsy in the early pregnancy is advisable in order to confirm if the next child is affected or not and if affected termination of pregnancy is advised.

4. Pre-Implantation Genetic Diagnosis

One of the newer techniques to avoid further children being born in a family with a history of Fanconi anaemia is the pre-implantation genetic diagnosis (PGD). In this method the sperm and eggs are fertilized outside of the uterus (In Vitro Fertilization) and the resultant embryos are tested for genetic defects. Among the fertilized embryos, an embryo that is healthy and without any genetic mutations will be transferred into the uterus. This can help the child be free from the gene mutations that run in the family.

Fanconi anaemia in children is a life-threatening disease. Children born with such kinds of genetic disorders are predisposed to cancers and bone marrow failure. Early diagnosis and frequent screening are helpful paths to getting better treatment that will work in the long term. Children born with Fanconi anemia need lifelong monitoring and psychological support to deal with the condition. It is very important to be in constant touch with your doctors in analyzing your child’s health condition and discussing the required treatments that can help your child lead a quality life.

FAQ’s

1. What is Fanconi Anaemia in Children?

Fanconi anaemia is a genetic disorder in which the child will be at high risk of having bone marrow failure and certain types of cancers, mainly acute myeloid leukaemia. Children with Fanconi anaemia can also have structural and internal organ anomalies.

2. Is Fanconi Anaemia Life-Threatening?

Yes, Fanconi anaemia is a life-threatening disease that comes with a high risk of bone marrow failure and developing cancers at an early age. Early diagnosis can help the child avoid serious health complications.

3. What is the Diagnosis For Fanconi Anaemia?

Children born with Fanconi anaemia tend to have a small head and other physical abnormalities. They have a tendency for bone marrow failure and the development of various cancers at a young age. Doctors may suggest a genetic screening if the infant is seen with any such symptoms. For toddlers and other children who grow up with Fanconi anaemia and do not have any physical abnormalities, they might need blood tests and a bone marrow biopsy to detect the condition.

4. Is There Any Cure For Fanconi Anaemia?

Fanconi anaemia is a genetic disorder that has treatments based on the condition the child is in. Hematopoietic Stem Cell Transplant is an effective treatment for the advanced stages of Fanconi anaemia. This can help the child receive healthy stem cells avoiding the risk of bone marrow failure and development of blood cancers.

Read Also: Sickle Cell Disease in Children: Symptoms, Diagnosis and Prevention by Dr. Stalin Ramprakash