Fanconi Anemia

Fanconi anemia (FA) is a clinically and genetically complex disorder. Typical clinical features include bone marrow failure, increased risk for cancer, physical abnormalities, and intellectual disability. Progressive bone marrow failure is responsible for the most significant morbidity and mortality. FA individuals are also at increased risk for multiple malignancies, including acute myelogenous leukemia, myelodysplasia, and solid tumors of the neck, head, oral cavities, and gynecological system. Approximately 70% of FA patients are born with abnormalities, which include abnormal dark or light skin spots, short stature, radial ray defects, abnormally small eyes, malformations of the kidney, genitalia, heart, gastrointestinal tract, ears, and feet. Currently there is no cure for FA, but medical surveillance and care may help to improve some symptoms and overall condition of life. Fanconi anemia is caused by pathogenic variants in 14 different genes. Fanconi anemia type C is caused by pathogenic variants in the FANCC gene.

FA is inherited in an autosomal recessive manner. This type of inheritance requires the presence of two copies of a pathogenic variant in the gene for a person to have the genetic disease. Both parents must be carriers of a pathogenic variant in the gene in order to be at risk to have an affected child. The child must inherit a pathogenic variant from each carrier parent in order to be affected. There is a 1 in 4 chance that a baby will inherit two mutated copies of the gene and be affected when both parents are carriers.

There are no signs or symptoms associated with being a carrier of FANNC pathogenic variants. However, the risk to have a child affected with Fanconi anemia is increased. FANCC pathogenic variant analysis is recommended for the reproductive partner of a known FANCC carrier.

Approximately 1 in 380 individuals in the general population is a carrier of a FANCC pathogenic variant. The carrier frequence in the Ashkenazi Jewish population is approximately 1 in 100.

Genetics Home Reference: Fanconi Anemia (http://ghr.nlm.nih.gov/)

OMIM [Fanconi anemia, complementation group C: 227645] (http://www.ncbi.nlm.nih.gov/omim)
Gene Reviews: Fanconi anemia (http://www.ncbi.nlm.nih.gov/books/NBK1116/)
NIH: Fanconi anemia (http://www.nhlbi.nih.gov)

• Full gene sequencing