Which are the causes of Fanconi Anemia?

Fanconi Anemia (FA) is a rare genetic disorder that primarily affects the bone marrow, leading to a decrease in the production of all types of blood cells. It is characterized by a wide range of physical abnormalities and an increased risk of developing certain cancers. FA is caused by mutations in any of the 22 known FA genes, which are involved in the repair of damaged DNA.

1. Inherited Mutations: The most common cause of Fanconi Anemia is inherited mutations in the FA genes. These mutations can be passed down from parents to their children in an autosomal recessive manner. This means that both parents must carry a mutated copy of the FA gene for their child to be affected. If both parents are carriers, there is a 25% chance with each pregnancy that the child will have FA.

2. Spontaneous Mutations: In some cases, individuals can develop FA due to spontaneous mutations that occur in their cells during early embryonic development. These mutations are not inherited from the parents but arise randomly. Spontaneous mutations can also occur in individuals with no family history of FA.

3. Chromosomal Abnormalities: Fanconi Anemia can also be caused by chromosomal abnormalities, such as large deletions or rearrangements involving the FA genes. These abnormalities can disrupt the normal functioning of the FA genes, leading to the development of FA.

4. Environmental Factors: While the primary cause of FA is genetic, certain environmental factors can increase the risk of developing the disorder. Exposure to certain chemicals, such as benzene and certain pesticides, has been linked to an increased risk of FA. Additionally, individuals with FA are more sensitive to the toxic effects of chemotherapy and radiation therapy, which are commonly used to treat cancer.

5. Other Genetic Syndromes: In rare cases, Fanconi Anemia can be associated with other genetic syndromes, such as VACTERL association or Diamond-Blackfan anemia. These syndromes have overlapping features with FA and can be caused by mutations in genes that are also involved in the FA pathway.

It is important to note that while the exact cause of FA is known, the underlying mechanisms by which FA gene mutations lead to the characteristic features of the disorder are still being studied. Researchers are actively working to understand the complex interactions between the FA genes and the DNA repair process to develop better treatments and interventions for individuals with Fanconi Anemia.