Fanconi anaemia and biallelic mutations in breast cancer risk genes

Fanconi Anaemia and Breast and Ovarian Cancer Risk Genes

Fanconi anaemia is rare, affecting 1 in 160,000 people.

It is usually caused by inheriting 2 pathogenic (disease causing) mutations in the same DNA repair gene. This is called biallelic inheritance (an allele refers to the particular version of a gene) and the condition is referred to as a recessive condition. In a recessive condition or syndrome you need 2 mistakes in the same gene, one from each parent, before the condition or syndrome occurs.

Fanconi anaemia is named after the Swiss paediatrian, Giuseppe Fanconi, who first described the syndrome in 1927.

Fanconi anaemia is very serious and usually results in bone marrow failure in childhood, requiring a bone marrow transplant. It also causes growth retardation, problems with the development of the thumb and/or forearm, a weakened immune system and other problems that may be detected at a very young age.

There are more than 20 genes known to cause Fanconi anaemia. They are usually named FANC + a letter of the alphabet. The following genes, known to increase breast and/or ovarian cancer risk when one mutation is inherited (autosomal dominant), cause Fanconi anaemia when biallelic mutations are inherited (autosomal recessive).

Because Fanconi anaemia affects children and many of the signs and symptoms are not treatable, some couples undertake preconception testing of a partner. That is, if someone carries a BRCA2 mutation, their partner may have genetic testing to make sure they don't carry a BRCA2 mutation as well. If they do, the chance of Fanconi anaemia is 1 in 4. Also, some couples use preimplantation genetic diagnosis (PGD) in the setting of in vitro fertilisation (IVF) to prevent the known familial mutation from either parent from being passed on to future generations.

Does this sound like you or your family? Has a BRCA1, BRCA2, BRIP1, PALB2 or RAD51C mutation been detected in a blood relative? Make an appointment with Dr Hilda High at Sydney Cancer Genetics. It is a confidential opportunity to discuss your personal and family history of cancer and genetic testing can be organised, if needed.