Suggested guidelines for genetic counselling of BRCA2 mutation carriers
| Scenario | Risk of an affected child with FA due to biallelic BRCA2 mutations | Suggested management | |
|---|---|---|---|
| Partner 1 | Partner 2 | ||
| AJ BRCA2 6174delT+ | AJ | Hypothetical risk No recorded cases with biallelic 6174delT mutations. Possibly higher risk of miscarriages. | Consider testing for AJ BRCA1/BRCA2 founder mutations in the partner, but limited indication for PND if partner also carries 6174delT. Consider offering full BRCA2 to the partner if their family history is suggestive of HBOC although non-founder mutations are infrequent in the AJ population.45 Consider screening for the AJ FANCC founder mutation. |
| Non-AJ BRCA2+ | AJ | Potential risk—1 in 400 or less. Combination may be embryonic lethal if non-AJ mutation in exon 11. | Consider offering testing for AJ BRCA1/BRCA2 founder mutations to the partner. Offer PGD/PND if the non-AJ partner carries a mutation. |
| Non-AJ BRCA2+ | Non-AJ | Potential risk (will depend on whether this is a population with founder mutations). Combination may be embryonic lethal if both mutations in exon 11. | Consider offering BRCA2 testing to the partner if their family history is suggestive of HBOC. Offer PGD/PND if the partner carries a mutation. |
Schematic guidelines for the risk assessment and management with respect to Fanconi anaemia and pregnancy outcome of BRCA2 mutation carriers.
AJ, Ashkenazi Jewish; FA, Fanconi anaemia; HBOC, hereditary breast and ovarian cancer; PGD, preimplantation genetic diagnosis; PND, prenatal diagnosis;