Causes and Risk Factors of Fanconi Anemia

Fanconi anemia (FA) is a rare hereditary disease. About 50% of cases are diagnosed before the age of 10, and an estimated 10% are diagnosed in adulthood.

The exact cause of FA is unknown, but research has shown that there is a strong genetic component to this disease. In people with FA, mutations in one or more genes associated with DNA repair lead to more frequent breaks in and rearrangements of genetic material, also known as chromosomal instability.

The inability to repair damaged DNA leads to a host of abnormalities at birth (congenital defects), blood disorders, and predisposition to a variety of cancer.

FA runs in families, so parents pass defective genes onto their children. Fanconi anemia is found in both genders and has no racial predilection. However, specific FA subtypes may be more prevalent in certain ethnic groups, like Ashkenazi Jews, Afrikaners, and the Roma population of Spain.

This article will discuss the causes and risk factors associated with Fanconi anemia.  

Common Causes

FA is primarily an autosomal recessive genetic disorder, which means that two mutated alleles (genes)—one from each biological parent—are required to cause the disease. In most cases, if a child inherits just one allele from a parent, they can be a carrier (able to pass the gene on to their children) but typically won't develop symptoms.

In rare cases, FA can be inherited in an autosomal dominant pattern, meaning only one allele is needed to cause the disease. This occurs only when specific gene mutations, such as RAD51, are passed on to offspring.

Genetics

In healthy cells, damage to DNA (genetic material) can be corrected, but this is not the case in those with FA. This condition is mainly caused by defects in the genes that provide instructions to help the body repair specific types of DNA damage.

Defects in at least 16 genes have been linked to the disease. Between 80% and 90% of gene mutations occur in one of three genes associated with DNA repair: FANCA, FANCC, and FANCG.

Mutations in the following genes may also cause FA and are inherited in an autosomal recessive manner: BRCA2, BRIP1, FANCB, FANCD2, FANCE, FANCF, FANCI, ERCC4, FANCL, FANCM, PALB2, RAD51C, SLX4, and UBE2T. The FANCB gene causes less than 1% of all cases of FA.

Other Risk Factors

FA occurs in all racial and ethnic groups and affects males and females equally, but there are three ethnic groups—Ashkenazi Jews (from eastern Europe), Afrikaners (South Africans of European descent), and the Roma population of Spain (also known as Gypsies)—that are more likely to have or be carriers of FA.

FA is rare, with an estimated 1 in 181 people in North America and 1 in 93 people in Israel having or being carriers for FA.

However, prevalence is higher among the three ethnic groups mentioned. It is estimated that 1 in 89 Ashkenazi Jews and 1 in 83 Afrikaners carry the genetic variant for FA, with roughly 1 in 32,000 developing the disease, compared to 1 in 160,000 in the general population.

The most associated mutations with each group are as follows:

• Ashkenazi Jews (FANCC, BRCA2/FANCD1)
• Northern Europeans (FANCC), 
• Afrikaners (FANCA) and sub-Saharan Blacks (FANCG)
• Spanish Roma (FANCA)

Lifestyle Risk Factors 

Fanconi anemia (FA) is hereditary. Genetics are an inalterable factor in the development of disease. Still, there are lifestyle factors like avoiding smoking, minimizing exposure to toxic chemicals and radiation, and adopting healthy habits that can help reduce your cancer risk and lessen medical complications of FA.

The eventual development of bone marrow failure can leave FA patients more vulnerable to opportunistic infections and more prone to injury. Because of this, it's also recommended to make certain lifestyle changes. This includes avoiding any activity that can cause bruising and bleeding when blood platelet levels are low and frequently washing hands to prevent infections.

It’s important to remember that FA is a chronic disease with no cure that starts showing signs and symptoms in early life. Therefore, it not only impacts the child physically but both the parents and child mentally.

As a result, it may help all family members to make modifications to improve their overall health. Ways to enhance your mental and physical health may include:

• Getting seven to nine hours of sleep
• Managing stress
• Exercising
• Maintaining a healthy diet
• Drinking enough fluids
• Eating healthy protein
• Consuming probiotics
• Frequently checking in with loved ones and trusted healthcare professionals

Summary

Fanconi anemia (FA) is a rare genetic condition. In most cases, FA is autosomal recessive in nature, which means that a person must receive two mutated genes—one from each biological parent—to have the disease. At least 16 gene mutations have been linked to FA. Three ethnic groups—Ashkenazi Jews, Afrikaners, and the Roma population of Spain—have a higher likelihood of having or being a carrier of FA.

A Word From Verywell 

Although the past two decades have brought about much more knowledge of the genetic foundations of FA, more research is needed to uncover all the causal factors.

If you or a loved one has FA, you may want to consider participating in research. Choosing to participate in a study is an important personal decision. If you are interested, talk with a trusted healthcare professional, and family members or friends about deciding to join a study. Many scientists believe that forwarding research in this way gives society the best chance at finding a cure for FA and many other rare diseases.