Understanding Fanconi Anemia and Its Cytogenetic Aspects

Understanding Fanconi Anemia and Its Cytogenetic Aspects

Fanconi Anemia (FA) is a rare genetic disorder characterized by bone marrow failure, congenital abnormalities, and a predisposition to cancer. This condition results from mutations in one of the 23 genes involved in the FA/BRCA DNA repair pathway1. These mutations impair the body’s ability to repair DNA damage, leading to various clinical manifestations.

Clinical Features

Bone Marrow Failure: Patients often experience aplastic anemia, where the bone marrow fails to produce sufficient blood cells

Congenital Abnormalities: These can include skeletal anomalies, skin pigmentation changes, and developmental delays

Cancer Predisposition: Individuals with FA have a higher risk of developing acute myeloid leukemia (AML) and solid tumors, particularly in the head and neck region2

Cytogenetic Analysis in FA: Cytogenetics plays a crucial role in diagnosing and managing Fanconi Anemia. The primary cytogenetic test involves assessing the sensitivity of patient cells to DNA crosslinking agents like diepoxybutane (DEB) or mitomycin C (MMC). These agents induce chromosomal breakage, which is significantly higher in FA cells compared to normal cells3

Diagnostic Process

Chromosomal Breakage Test: This test is the gold standard for diagnosing FA. It involves exposing patient lymphocytes to DEB or MMC and then analyzing the chromosomal aberrations

Molecular Genetic Testing: Identifying mutations in the FA genes can confirm the diagnosis and help in genetic counseling and family planning4

Management and Treatment

Hematopoietic Stem Cell Transplantation (HSCT): This is the only curative treatment for bone marrow failure in FA patients. However, it comes with risks, including increased susceptibility to malignancies2

Gene Therapy: Still experimental, gene therapy aims to correct the genetic defects in hematopoietic stem cells2

Regular Monitoring: Due to the high risk of cancer, patients require lifelong surveillance and early intervention for malignancies2

Fanconi Anemia is a complex disorder requiring a multidisciplinary approach for effective management. Advances in cytogenetic and molecular techniques continue to improve diagnostic accuracy and patient outcomes