FaCD Online Syndrome Fact Sheet

Last updated: 29 Feb 2008

Name: Fanconi Anemia type D1, bi-allelic BRCA2 mutations

Synonym: FANCD1

Mode of Inheritance: AR

OMIM number: 605724  

Genes

BRCA2, mapped to 13q12.3

Tumor features

astrocytoma
leukemia, acute lymphoblastic (ALL)
leukemia, acute myeloid (AML, incl. ANLL)
medulloblastoma
Wilms' tumor (nephroblastoma)

Non-tumor features

anemia
café au lait spots
imperforate anus
microcephaly
mutagen sensitivity, increased
short stature
thumbs, hypoplastic or absent

Comment

Childhood cancer is not a characteristic of families with BRCA2 mutations[1]. However, bi-allelic germline BRCA2 mutations cause Fanconi Anemia (FA) type D1 and are associated with medulloblastoma, astrocytoma, acute leukemia, and Wilms tumor. Other physical characteristics as generally seen in FA an be observed as well, including VATER/VACTERL-H features.[2-5]. Alter et al[4] estimated a cumulative probability of developing any type of cancer of 97% by age 5.2 years in carriers of bi-allelic BRCA2 mutations. Some of the mutations are missense mutations and breast cancer risks for carriers of these single mutations are not yet clear.

References

[1] Brooks GA, Stopfer JE, Erlichman J, Davidson R, Nathanson KL, Domchek SM. Childhood cancer in families with and without BRCA1 or BRCA2 mutations ascertained at a high-risk breast cancer clinic. Cancer biology & therapy 2006; 5(9):1098-102.
[2] Howlett NG, Taniguchi T, Olson S, Cox B, Waisfisz Q, De Die-Smulders C, Persky N, Grompe M, Joenje H, Pals G, Ikeda H, Fox EA, D'Andrea AD. Biallelic inactivation of BRCA2 in Fanconi anemia. Science (New York, N.Y.) 2002; 297(5581):606-9.
[3] Offit K, Levran O, Mullaney B, Mah K, Nafa K, Batish SD, Diotti R, Schneider H, Deffenbaugh A, Scholl T, Proud VK, Robson M, Norton L, Ellis N, Hanenberg H, Auerbach AD. Shared genetic susceptibility to breast cancer, brain tumors, and Fanconi anemia. Journal of the National Cancer Institute 2003; 95(20):1548-51.
[4] Alter BP, Rosenberg PS, Brody LC. Clinical and molecular features associated with biallelic mutations in FANCD1/BRCA2. Journal of medical genetics 2007; 44(1):1-9.
[5] Wagner JE, Tolar J, Levran O, Scholl T, Deffenbaugh A, Satagopan J, Ben-Porat L, Mah K, Batish SD, Kutler DI, MacMillan ML, Hanenberg H, Auerbach AD. Germline mutations in BRCA2: shared genetic susceptibility to breast cancer, early onset leukemia, and Fanconi anemia. Blood 2004; 103(8):3226-9.