Fanconi Anemia: Symptoms, Causes & Treatment

Fanconi anemia is a rare genetic disorder that affects how the bone marrow makes blood cells. It can cause symptoms such as skin spots, scoliosis, short stature, and congenital abnormalities affecting the thumbs, bones, kidneys, or heart.

This condition gradually damages the bone marrow, so it produces fewer and fewer blood cells and may eventually stop making them altogether. As a result, it can cause aplastic anemia and also increase the risk of cancers such as leukemia.

Treatment for Fanconi anemia is managed by a hematologist and usually includes blood transfusions or a bone marrow transplant, depending on the person’s needs. Regular cancer screening is also very important so any cancer can be found as early as possible.

Main symptoms

The main symptoms of Fanconi anemia are:

• Low birth weight and shorter-than-expected height for age

• Café-au-lait spots on the skin

• An absent, short, or duplicated thumb

• A shortened arm, clubfoot, or hip dislocation

• Microcephaly or hydrocephalus

• A small mouth, chin, and eyes

Other physical features of Fanconi anemia may also include abnormalities of the ears or eyes, for example.

The child may also have hypogonadism and differences in genital development, such as missing or undescended testicles after birth, phimosis, an abnormal urethral opening, a small penis (micropenis), or an absent or closed vaginal canal.

Low levels of red blood cells, white blood cells, and platelets can also lead to symptoms such as easy or hard-to-control bleeding, unexplained bruises, feeling weak or dizzy, looking pale, and having frequent infections.

Confirming a diagnosis

Fanconi anemia may be suspected by a pediatrician based on the child’s symptoms, physical characteristics, medical history, family history of Fanconi anemia, and findings from the physical exam.

Blood tests, such as a complete blood count (CBC), myelogram, and bone marrow biopsy, together with imaging tests like ultrasound, magnetic resonance imaging (MRI), and X-rays, can help detect problems and deformities associated with the disease.

The diagnosis is typically confirmed with a genetic test called a chromosome breakage test, which detects DNA breaks or mutations in blood cells. Treatment is then managed by a hematologist.

Possible causes

Fanconi anemia is caused by genetic mutations in FA genes, which are responsible for repairing DNA damage. These mutations lead to DNA breakage or instability, which can cause abnormal cell growth that leads to cancer or the death of blood cells.

In most cases, Fanconi anemia is hereditary, meaning it is inherited in an autosomal recessive pattern from defective genes passed down by both parents. This means that for a child to be born with the condition, both parents must carry the gene mutation.

Although less common, Fanconi anemia may also be linked to an abnormal gene on the X chromosome. In these cases, the disease appears in male children, while girls are only carriers of the altered gene and do not develop the condition.

Fanconi anemia can also be autosomal dominant, which means it may be located in any gene other than X or Y, and only one altered copy of the gene is needed to cause the disease. In these cases, a RAD51 gene mutation is involved, and there is a 50% chance that a parent will pass the altered gene on to their child.

Treatment options

Treatment for Fanconi anemia should be managed by a hematologist, who may recommend red blood cell or platelet transfusions, or the use of filgrastim, a medicine that helps increase neutrophils in the blood and prevent infections.

Another treatment the doctor may recommend is androgen therapy, such as oxymetholone, danazol, or oxandrolone, especially in cases of anemia, because these medicines can help stimulate red blood cell production.

When the bone marrow fails and can no longer produce blood cells, hematopoietic stem cell transplantation (also called bone marrow transplantation) is, according to the National Cancer Institute, the only curative treatment for Fanconi anemia.

Surgery may also be recommended to correct abnormalities or deformities in the bones or other organs.

Care measures

It is very important for a person with Fanconi anemia to take certain precautions, such as:

• Having regular cancer screening tests for early detection

• Not smoking

• Avoiding alcoholic beverages

• Getting the HPV vaccine

• Avoiding exposure to radiation such as X-rays

• Avoiding excessive sun exposure or sun exposure without protection

It is also important to attend all medical appointments and follow up with other specialists who may notice changes, such as a dentist, ENT specialist, urologist, gynecologist, or speech therapist.

People with this syndrome, along with their families, should also have regular follow-up and counseling with a medical geneticist, who can recommend appropriate testing and identify relatives who may have the condition or be at risk of passing it on to their children.

Life expectancy

Fanconi anemia is most often diagnosed around 7 years of age, and life expectancy ranges from 20 to 30 years.

The earlier the disease is diagnosed and the sooner medical follow-up and treatment begin, the better life expectancy may be, although this varies from case to case.

Possible complications

According to the Fanconi Cancer Foundation Clinical Care Guidelines, patients with Fanconi anemia are at increased risk of developing myelodysplastic syndrome and acute myeloid leukemia (AML).

In addition, this disease also increases the risk of other types of cancer, such as skin cancer, head and neck cancer, esophageal cancer, gastrointestinal cancer, or cancer of the anus, vulva, or cervix, for example.

Fanconi anemia may also cause endocrine problems, such as hypothyroidism, glucose intolerance, increased LDL (“bad”) cholesterol and triglycerides, low HDL (“good”) cholesterol, or infertility due to hypogonadism.