FaCD Online Syndrome Fact Sheet

Last updated: 28 Jan 2011


Synonym: Pancytopenia Dysmelia, FA (several complementation groups)

Mode of Inheritance: AR, XLR

OMIM number: 227650  


BRCA2, mapped to 13q12.3
FANCA, mapped to 16q24.3
FANCB, mapped to Xp22.31
FANCC, mapped to 9q22.3
FANCD1, mapped to 13q12.3
FANCD2, mapped to 3p25.3
FANCE, mapped to 6p21-p22
FANCF, mapped to 11p15
FANCG/XRCC9, mapped to 9p13
FANCI, mapped to 15q25-q26
FANCJ, mapped to 17q22
FANCL, mapped to 2p16.1
FANCM, mapped to 14q21.3
FANCP/SLX4, mapped to 16p13.3
PALB2/FANCN, mapped to 16p12

Tumor features

anal cancer
breast cancer
cervical cancer
esophageal cancer
gastric cancer
hepatic adenomas
hepatocellular cancer (hepatoma)
leukemia, acute myeloblastic (AML, M2)
leukemia, acute myeloid (AML, incl. ANLL)
myelodysplastic syndrome (MDS)
oropharyngeal cancer
tongue cancer
vulvar squamous cell cancer

Tumor features (possible)

hepatic nodular hyperplasia
myelodysplastic syndrome (MDS)
renal cell cancer
skin cancer, basal cell
skin cancer, squamous cell
Wilms' tumor (nephroblastoma)

Non-tumor features

café au lait spots
fetal hemoglobin, persistent
growth deficieny
increased chromosomal breakage
mutagen sensitivity, increased
ocular anomalies
radius abnormalities
renal anomalies
short stature

Non-tumor features (possible)

UV radiation sensitivity, increased


Fanconi Anemia (FA) is characterized by progressive bone marrow failure (pancytopenia/aplastic anemia in > 80 % of cases), usually presenting between 5 and 10 years, low birth weight, short stature, cafe au lait spots of the skin, radial skeletal anomalies (including hypoplasia or agenesis of the thumb) and renal defects. Of all FA patients, 20-40% have no significant birth defects. A wide range of congenital abnormalities has been reported in this disorder. Approximately 20 % of the patients have a mental deficiency. Cytogenetic studies show increased chromosomal breakage and structural abnormalities, especially after induction with crosslinking mutagen chemicals like mitomycin C. Elevated fetal hemoglobin is another laboratory finding.

In a review of all published cases of FA, Alter[1][editorial comment: will be updated with the 2003 reviews] found one or more malignancies in 15 % of the patients. More specific: leukemia (predominantly acute myeloblastic leukemia and acute monomyelocytic leukemia [2]) was found in 9 % of cases, at a mean age of 14 years (range 1 month-29 years). AML may be a presenting symptom[14]. Myelodysplastic syndrome[3] was found in 3 % of cases, at an average age of 17 years (range 5-31 years). Liver tumors are diagnosed in 5 % of FA patients: predominantly hepatocellular cancer and adenomas, at a mean age of 16 years (range 3-48 years), nodulart hyperplasia has been reported as well[13]. Other types of tumors have been reported in 5 % of the FA patients, at an average age of 23 years (range 4 months-38 years) with an unexplained excess of female (3:1) even after exclusion of the gynecological tumors. Most patients had squamous cell cancer. The most frequent tumors were:

  • oropharyngeal cancer (including the tongue)(has been diagnosed as young as the early teens)[8,11,12]
  • gastrointestinal ( mainly esophagus, anus and stomach)
  • Vulva, breast and cervix cancer
  • Brain tumors (astrocytoma, medulloblastoma)[4]
A number of tumors have been reported less frequently: renal cell cancer, Wilms tumor, retinoblastoma, skin cancer (basal cell and squamous cell), eyelid cancer (Bowen). Deeg et al.[5] demonstrated that Fanconi Anemia was a significant risk factor for developing solid tumors (mainly squamous cell cancer) after bone marrow transplantation. Development of leukemia in FA appears to be associated with a poor prognosis. Auerbach and Allen[2] reported a mean age of death in FA leukemia patients of 15 years.

It is presently unclear if there is a increased cancer risk in FA heterozygotes[6,10]. In a recent study there was no increased risk for cancer among FA heterozygotes although there was some evidence that FANCC mutations increase breast cancer risk[9]. A germline heterozygous truncating FANCC mutation has been detected in 2 sibs with T-ALL[7].
Fanconi anemia is genetically heterogeneous and is associated with mutations in at least 15 genes. FAA is responsible for approximately 2/3 of all cases.


Fanconi Anemia Research Fund, Inc. 18 1 08
Fanconi Mutation Database (Rockefeller) 28 5 2008
International Fanconi Anemia Registry (IFAR) 23 1 08
UK Fanconi Anaemia Clinical Network 29 6 09


[1] Alter BP. Fanconi's anemia and malignancies. Am J Hematol 53[2], 99-110. 1996.
[2] Auerbach AD, Allen RG. Leukemia and preleukemia in Fanconi anemia patients. A review of the literature and report of the International Fanconi Anemia Registry. Cancer Genet Cytogenet 1991; 51(1):1-12.
[3] Hasle H, Kerndrup G, Jacobsen BB. Childhood myelodysplastic syndrome in Denmark: incidence and predisposing conditions. Leukemia 1995; 9:1569-1572.
[4] Alter BP, Tenner MS. Brain tumors in patients with Fanconi's anemia. Arch Pediatr Adolesc Med 1994; 148(6):661-663.
[5] Deeg HJ, Socie G, Schoch G, Henry-Amar M, Witherspoon RP, Devergie A, Sullivan KM, Gluckman E, Storb R. Malignancies after marrow transplantation for aplastic anemia and Fanconi anemia: a joint Seattle and Paris analysis of results in 700 patients. Blood 1996; 87(1):386-392.
[6] Swift M, Caldwell RJ, Chase C. Reassessment of cancer predisposition of Fanconi anemia heterozygotes. J Natl Cancer Inst 1980; 65(5):863-867.
[7] Rischewski JR, Clausen H, Leber V, Niemeyer C, Ritter J, Schindler D, Schneppenheim R. A heterozygous frameshift mutation in the Fanconi anemia C gene in familial T-ALL and secondary malignancy. Klin Padiatr 2000; 212(4):174-176.
[8] Reinhard H, Peters I, Gottschling S, Ebell W, Graf N. Squamous cell carcinoma of the tongue in a 13-year-old girl with Fanconi anemia. Journal of pediatric hematology/oncology : official journal of the American Society of Pediatric Hematology/Oncology 2007; 29(7):488-91.
[9] Berwick M, Satagopan JM, Ben-Porat L, Carlson A, Mah K, Henry R, Diotti R, Milton K, Pujara K, Landers T, Dev Batish S, Morales J, Schindler D, Hanenberg H, Hromas R, Levran O, Auerbach AD. Genetic heterogeneity among Fanconi anemia heterozygotes and risk of cancer. Cancer research 2007; 67(19):9591-6.
[10] Mathew CG. Fanconi anaemia genes and susceptibility to cancer. Oncogene 2006; 25(43):5875-84.
[11] Köksal Y, Varan A, Hosal S, Büyükpamukçu M. Hypopharyngeal squamous cell carcinoma in a child. International journal of pediatric otorhinolaryngology 2005; 69(7):989-91.
[12] Salum FG, Martins GB, de Figueiredo MA, Cherubini K, Yurgel LS, Torres-Pereira C. Squamous cell carcinoma of the tongue after bone marrow transplantation in a patient with Fanconi anemia. Brazilian dental journal 2006; 17(2):161-5.
[13] Nuamah NM, Hamaloglu E, Ozdemir A, Ozenc A, Sozseker C, Sokmensuer C. Hepatic focal nodular hyperplasia developing in a Fanconi anemia patient: a case report and literature review. Haematologica 2006; 91(8 Suppl):ECR39.
[14] Meyer S, Barber LM, White DJ, Will AM, Birch JM, Kohler JA, Ersfeld K, Blom E, Joenje H, Eden TO, Malcolm Taylor G. Spectrum and significance of variants and mutations in the Fanconi anaemia group G gene in children with sporadic acute myeloid leukaemia. British journal of haematology 2006; 133(3):284-92.
[15] Rosenberg PS, Greene MH, Alter BP. Cancer incidence in persons with Fanconi anemia. Blood 2003; 101(3):822-6.
[16] Alter BP. Cancer in Fanconi anemia, 1927-2001. Cancer 2003; 97(2):425-40.
[17] Rosenberg PS, Alter BP, Ebell W. Cancer risks in Fanconi anemia: findings from the German Fanconi Anemia Registry. Haematologica 2008; 93(4):511-7.