Genetic studies by NGS Panels

Fanconi anemia panel (Code 10090)


Fanconi anemia (FA) (OMIM #227645, #227645, #227646, #227650, #300514, #600901, #603467, #609053, #609054, #610832,  #613390,  #613951,  #614082,  #614083,  #615272, #616435, #617243, #617244, #617247) is a complex inherited disorder where genes involved in DNA repair and genomic stability are affected. 22 genes associated with the disease have been identified.

The pattern of inheritance is usually autosomal recessive but there have been described cases with an X-linked transmission (FANCB gene) and cases of autosomal dominant inheritance (FANCR gene). Mutations of the FANCA gene are the most represented (70-80% in our environment).

The initial diagnostic test should be the evaluation of chromosomal fragility in lymphocytes induced by diepoxybutane (DEB) or mitomycin (MMC). In uncertain or negative cases with high clinical suspicion, the study in fibroblasts should be performed due to the phenomenon of somatic mosaicism. To complete the diagnosis of FA it is essential the characterization of the subtype and pathogenic mutations of the disease, since it confirms the diagnosis and enables the detection of carriers, as well as facilitates prenatal and pre-implantation diagnosis.

The estimated heterozygous carrier frequency is 0.3-1%, with an expected prevalence of at least 1-9 / 1,000,000 births. In some populations, the frequency of carriers is much higher, due to founder mutations, although it is distributed by all races and ethnic groups. To date, more than 2,000 cases have been described.


Regarding clinical manifestations, bone marrow failure usually appears around 7 years of age. In the course of the disease, 90-98% of patients will develop marrow failure before age 40. This characteristic, as well as the higher incidence of tumors, seem related to many other factors and not only to DNA damage: an excess of free oxygen radicals has been described in Fanconi cells, as well as some mitochondrial defects. Patients may develop acute myeloid leukemia, often preceded by myelodysplastic syndrome; They are also very predisposed to develop solid tumors in the head, neck or anogenital region. In 2/3 of patients, the first signs of AF are congenital malformations that can affect the skeleton, the skin, and the urogenital, cardiopulmonary, gastrointestinal, and central nervous systems. Minor abnormalities such as low weight and height, microcephaly, and / or microphthalmia may also occur. Abnormalities in the pigmentation and hypoplasia of thenar eminence are frequent. Almost 20% of patients have ear malformations. Congenital malformations can vary in the same family. When congenital malformations are not prominent, the diagnosis may be delayed until the onset of bone marrow failure. Fertility is very damaged in men, and very affected in half of women. Pregnancy is often complicated.


AF should be considered in all cases of young patients with bone marrow failure of unknown origin. In the differential diagnosis, other syndromes predisposing to cancer or with pancytopenia should be considered (Diamond-Blackfan anemia, immune pancytopenia).

Supportive treatment includes transfusions of packed red cells or platelets. The only curative treatment for haematological manifestations is the transplantation of hematopoietic progenitor cells (HSCT). In HSCT from family donors, the use of reduced intensity conditioning with fludarabine and depletion of T lymphocytes in the inoculum is giving excellent results, with improved survival and decreased incidence of secondary neoplasms. Unfortunately, in most cases there is no family donor so it is necessary to resort to unrelated donors or the umbilical cord. Survival is around 70%. However, this process tends to increase the risk of solid tumor, which must be followed with special attention. Gene therapy is in very advanced stages of research. Symptomatic treatment includes the administration of oral androgens, which improves blood parameters, especially the number of red blood cells. The administration of hematopoietic growth factors should be considered if necessary. As malignant tumors develop, the treatment becomes more complicated due to the patient’s radiation sensitivity and chemotherapy.


Bone marrow insufficiency and malignant tumors lead to an unfavorable prognosis with a reduced life expectancy, which has improved thanks to HSCT and androgen treatment.


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