Fanconi Anemia (FANCC-related)
Fanconi anemia (FA) is an inherited disorder in DNA repair characterized by progressive pancytopenia with bone marrow failure, congenital malformations variables and predisposition to develop solid or hematological tumors.
The carrier frequency is estimated at more than 1/200, with an expected prevalence at birth of at least 1 / 160,000.
In some populations, the carrier frequency is much higher. To date, there have been more than 2,000 cases described in the literature. The FA is usually an autosomal recessive disorder but in some cases have been reported with a transmission X-linked.
It is caused by mutations in genes involved in DNA repair and genomic stability. They have identified 15 genes representing 15 complementation groups.
Given the high heterogeneity in the genetic causes and clinical phenotype, and in the pathogenic mechanism of FA, the diagnosis is based on the assessment of chromosomal breakage induced by diepoxybutane (DEB) or mitomycin (MMC).
The clinical manifestations of FA overlap with those of many malformation syndromes and their diagnosis is usually delayed until the patient developed bone marrow failure or malignant tumors. FA should be considered in all cases of young patients with bone marrow failure of unknown origin. Other cancer predisposition syndromes or pancytopenia (anemia Diamond-Blackfan, immune pancytopenia) should be considered.
Prenatal diagnosis is possible by testing DEB-induced chromosomal breakage or a molecular study if the mutation is known.
In 2/3 patients, early signs of FA are congenital malformations that can affect the skeleton, skin and cardiopulmonary, urogenital, gastrointestinal and central nervous systems. The limb abnormalities are unilateral or bilateral. They can also occur minor anomalies such as low weight and stature, microcephaly and/or microphthalmia. They are frequent pigmentation abnormalities and hypoplasia of thenar. Almost 20% of patients have ear malformations. Congenital malformations may vary within the same family. When congenital malformations are not prominent, the diagnosis may be delayed until the onset of bone marrow failure, about 7 years old. Hematologic abnormalities can occur at a younger age and in adults. The 90% of patients develop bone marrow failure before 40 years. Patients may develop acute myeloid leukemia, often preceded by myelodysplastic syndrome. Patients are highly predisposed to develop solid tumors in head, neck or anogenital region. Fertility in men is badly damaged, and very affected in half of women. Pregnancy is often complicated.
Gene or region studied