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

J Med Genet. 2022 Sep;59(9):912-915. doi: 10.1136/jmedgenet-2021-108072. Epub 2021 Oct 25.

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.

Keywords: gastrointestinal diseases; genetic predisposition to disease; genetic testing; medical oncology; phenotype.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma*
  • BRCA2 Protein / genetics
  • Breast Neoplasms*
  • Fanconi Anemia* / diagnosis
  • Fanconi Anemia* / genetics
  • Fanconi Anemia* / pathology
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Phenotype

Substances

  • BRCA2 Protein
  • BRCA2 protein, human

Supplementary concepts

  • Breast Cancer, Familial
  • Fanconi Anemia, Complementation Group D1