Catastrophic chemotherapy toxicity leading to diagnosis of Fanconi anaemia due to FANCD1/BRCA2 during adulthood: description of an emerging phenotype. Issue 9 (25th October 2021)

• Record Type: Journal Article
• Authors: Ip, Emilia; McNeil, Catriona; Grimison, Peter; Scheinberg, Tahlia; Tudini, Emma; Ho, Gladys; Scott, Rodney J; Brown, Christina; Sandroussi, Charbel; Guitera, Pascale; Spurdle, Amanda B; Goodwin, Annabel
• Is Part Of: Journal of medical genetics. Volume 59:Issue 9(2022)
• Page Start: 912
• Page End: 915
• Publication Date: 2021-10-25
• Subjects: genetic testing -- medical oncology -- phenotype -- gastrointestinal diseases -- genetic predisposition to disease; Medical genetics -- Periodicals; 616.042
• DOI: 10.1136/jmedgenet-2021-108072
• Languages: English
• ISSNs: 1468-6244

Abstract

Abstract : Fanconi anaemia due to biallelic loss of BRCA2 (Fanconi anaemia subtype D1) is traditionally diagnosed during childhood with cancer rates historically reported as 97% by 5.2 years. 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.