Catastrophic chemotherapy toxicity leading to diagnosis of Fanconi anaemia due to FANCD1/BRCA2 during adulthood: description of an emerging phenotype

This report describes an adult woman with a history of primary ovarian failure, who was diagnosed with gastrointestinal adenocarcinoma and BRCA2-associated Fanconi anaemia at 23 years of age, only after she suffered severe chemotherapy toxicity. The diagnostic challenges include atypical presentation, initial false-negative chromosome fragility testing and variant classification. It highlights gastrointestinal adenocarcinoma as a consideration for adults with biallelic BRCA2 pathogenic variants with implications for surveillance. After over 4 years, the patient has no evidence of gastrointestinal cancer recurrence although the tumour was initially considered only borderline resectable. The use of platinum-based chemotherapy, to which heterozygous BRCA2 carriers are known to respond, may have had a beneficial anticancer effect, but caution is advised given its extreme immediate toxicity at standard dosing. Fanconi anaemia should be considered as a cause for women with primary ovarian failure of unknown cause and referral to cancer genetic services recommended when there is a family history of cancer in the hereditary breast/ovarian cancer spectrum.

Source: Journal of Medical Genetics - August 19, 2022 Category: Genetics & Stem Cells Authors: Ip, E., McNeil, C., Grimison, P., Scheinberg, T., Tudini, E., Ho, G., Scott, R. J., Brown, C., Sandroussi, C., Guitera, P., Spurdle, A. B., Goodwin, A. Tags: Cancer genetics Source Type: research