Fanconi Anemia (FA) is an inherited bone marrow failure syndrome featuring pancytopenia, predisposition to malignancy and characteristic physical abnormalities such as short stature, developmental delay, thumb abnormalities, among others. It is the most frequently reported of the rare inherited bone marrow failure syndromes. Individuals with FA require increased surveillance for malignancies and organ dysfunction. The defect relies in the inability to repair deleterious types of DNA damage resulting in genomic instability which in turn leads to increased risk of malignancy and defective haematopoiesis. In most cases, FA is inherited in an autosomal recessive manner although X-linked and autosomal dominant patterns exist.
The Igenomix Fanconi Anemia Precision Panel can be used to make an accurate and directed diagnosis as well as a differential diagnosis of pancytopenia ultimately leading to a better management and prognosis of the disease. It provides a comprehensive analysis of the genes involved in this disease using next-generation sequencing (NGS) to fully understand the spectrum of relevant genes involved.
- The Igenomix Fanconi Anemia Precision Panel is indicated for those patients with a clinical suspicion or diagnosis with or without the following manifestations:
- Short stature
- Skin pigmentation
- Frequent infections
- Thumb or other radial ray abnormalities
- Other malformations: congenital heart disease, gastrointestinal anomalies, CNS anomalies etc
The clinical utility of this panel is:
- The genetic and molecular confirmation for an accurate clinical diagnosis of a symptomatic patient.
- Early initiation of treatment with a multidisciplinary team in the form hematopoietic stem cell transplantation as well as preventive measures such as active restriction, management of acute complications and early and continuous surveillance of malignancy.
- Risk assessment and genetic counselling of asymptomatic family members according to the mode of inheritance.
- Improvement of delineation of genotype-phenotype correlation.
D’Andrea, A. D., & Grompe, M. (2003). The Fanconi anaemia/BRCA pathway. Nature reviews. Cancer, 3(1), 23–34. https://doi.org/10.1038/nrc970
De Rocco, D., Bottega, R., Cappelli, E., Cavani, S., Criscuolo, M., Nicchia, E., Corsolini, F., Greco, C., Borriello, A., Svahn, J., Pillon, M., Mecucci, C., Casazza, G., Verzegnassi, F., Cugno, C., Locasciulli, A., Farruggia, P., Longoni, D., Ramenghi, U., Barberi, W., … Bone Marrow Failure Study Group of the Italian Association of Pediatric Onco-Hematology (2014). Molecular analysis of Fanconi anemia: the experience of the Bone Marrow Failure Study Group of the Italian Association of Pediatric Onco-Hematology. Haematologica, 99(6), 1022–1031. https://doi.org/10.3324/haematol.2014.104224
Chromosome instability syndromes. (2019). Nature Reviews Disease Primers, 5(1). doi: 10.1038/s41572-019-0123-y
Kottemann, M. C., & Smogorzewska, A. (2013). Fanconi anaemia and the repair of Watson and Crick DNA crosslinks. Nature, 493(7432), 356–363. https://doi.org/10.1038/nature11863
Kee, Y., & D’Andrea, A. D. (2010). Expanded roles of the Fanconi anemia pathway in preserving genomic stability. Genes & development, 24(16), 1680–1694. https://doi.org/10.1101/gad.1955310
Thompson L. H. (2005). Unraveling the Fanconi anemia-DNA repair connection. Nature genetics, 37(9), 921–922. https://doi.org/10.1038/ng0905-921